An innovative combination of existing technologies shows promise for noninvasive, high-resolution imaging of cartilage in research on the progression and treatment of the common degenerative disease osteoarthritis.
Microcomputed tomography (microCT) - which yields three-dimensional X-ray images with a resolution 100 times higher than clinical CT scans - is commonly used to image bone for osteoporosis research but has not been useful for imaging soft biological tissues such as cartilage. These tissues simply don't interfere with the microCT's X-rays as they pass through a sample, and therefore don't show up on scans.
But by combining microCT with an X-ray-absorbing contrast agent that has a negative charge, researchers at the Georgia Institute of Technology were able to image the distribution of negatively charged molecules called proteoglycans (PGs). These molecules are critical to the proper functioning of cartilage.
"By detecting PG content and distribution, the technique reveals information about both the thickness and composition of the cartilage -- important factors for monitoring the progression and treatment of osteoarthritis," said Associate Professor Marc Levenston in Georgia Tech's George W. Woodruff School of Mechanical Engineering.
He and Associate Professor Robert Guldberg, also in the School of Mechanical Engineering, collaborated to establish and validate the principle of the technique, dubbed Equilibrium Partitioning of an Ionic Contrast agent-microCT, or EPIC-microCT. Then they applied the technique in vitro to monitor the degradation of bovine cartilage cores and to visualize the thin layer of cartilage in an intact rabbit knee.
"This technique will allow pharmaceutical researchers to obtain more detailed information about the effects of new drugs and other treatment strategies for treating osteoarthritis," Levenston said.
A report on the research will be published Dec. 12 issue in the journal Proceedings of the National Academy of Science of the United States of America and will appear in the only early edition during the week of Dec. 4. The National Science Foundation, National Institute of Arthritis and Musculoskeletal and Skin Disorders, and the Arthritis Foundation funded the work.
Experiments conducted by Ph.D. student Ashley Palmer established the principles and protocol of EPIC-microCT. Researchers first immersed cartilage samples in the contrast agent solution and waited for the agent to diffuse into the tissue. Tissue with fewer negatively charged PGs absorbed more of the negatively charged contrast agent, and tissue with a higher PG concentration repelled it.
Researchers then used EPIC-microCT to detect the concentrations of the contrast agent, which allowed them to calculate the amount of PGs in different parts of the cartilage. Because degrading cartilage loses PGs over time, researchers could monitor the progression of tissue changes. In addition, differences in the X-ray signal of cartilage and bone allowed researchers to isolate the cartilage layer on a rabbit joint and determine its thickness, indicating that this technique also can be used to measure tissue thinning during disease progression.
In follow-on research funded by a new, two-year grant from the National Institutes of Health, the researchers will gather additional quantitative data and use the technique to examine the very thin cartilage of rat knee joints. Researchers will nondestructively evaluate osteoarthritis progression and then attempt to use this approach to monitor cartilage changes over time in vivo, or inside the same live animals.
"Ultimately, if we can monitor cartilage changes with good resolution and do it with little or no invasion of the tissue in live animals, then we can track osteoarthritis progression and the effects of drug therapy or other treatments over time," Guldberg said.
Researchers have already addressed a significant technical hurdle in making the imaging technique feasible. They researched several contrast agents and tried two others before choosing HexabrixTM, which is approved by the Food and Drug Administration for use as a contrast agent for various imaging procedures in humans. When diluted, it produced an X-ray signal that allowed distinction of bone from cartilage.
"The ability to separate bone from cartilage in the microCT scan is a big deal," Guldberg said. "It suggests that this technique may work in vivo."
But dilution reduces the contrast agent's sensitivity and therefore the technique's PG-monitoring capability, the authors write in their paper. "In this next phase of research, we hope to find a one-shot concentration of the contrast agent that works for analyzing both cartilage thickness and composition," said Levenston, the lead author on the paper.
In addition, the researchers must address technical issues involving the in vivo delivery and retention of a sufficient volume and concentration of the contrast agent, they note in the paper.
"But even if the technique only works for in vitro studies, it still provides useful quantitative, high-resolution, 3D images that researchers can use to nondestructively monitor cartilage degeneration and even regeneration in small animal models," Guldberg said.
TECHNICAL CONTACTS:
1. Marc Levenston
2. Robert Guldberg
3. Ashley Palmer
WRITER: Jane M. Sanders
Contact: Jane M. Sanders
Georgia Institute of Technology Research News
суббота, 30 апреля 2011 г.
пятница, 29 апреля 2011 г.
Dose Escalation With Enbrel(R) Is Significantly Lower Than Other Commonly Used Anti-TNF Agents In Patients With Rheumatoid Arthritis, DART Study, UK
New pan-European data presented at the British Society of Rheumatology's annual meeting in Liverpool demonstrate that patients treated with Enbrel® (etanercept) required significantly lower dose escalation than patients treated with infliximab and adalimumab in the first 12 months of therapy. The latter two anti-TNF agents (ATAs) for the treatment of rheumatoid arthritis are monoclonal antibodies while etanercept is a soluble TNF receptor.
The DART* study assessed current clinical practice in the treatment of rheumatoid arthritis patients by comparing potential dose escalation in three selected ATAs and their associated costs of treatment.1 The results of the 44 European centre study showed that the dose escalation to maintain clinical response was less than 1 per cent with etanercept compared to 8 per cent with adalimumab and 29 per cent with infliximab in the first 12 months. In those study centres where there were no restrictions to prescribing ATAs, the results showed a 2 per cent dose escalation with etanercept versus 11 per cent and 35 per cent respectively, indicating that associated cost increments were negligible with etanercept.1
"The results of the DART study add to the body of evidence that etanercept achieves sustained efficacy without the need for dose escalation in 99 per cent of patients studied and thus demonstrates a cost effective treatment option for patients with rheumatoid arthritis over both the short and long term," said Professor Robert Moots, Professor of Rheumatology, University of Liverpool, Liverpool, United Kingdom and DART study investigator. "The current perception of biological therapy for inflammatory conditions such as rheumatoid arthritis is that it can be costly, however if the long term outlook and patient quality of life is taken into consideration, biologics such as etanercept are extremely cost effective. This is important both for physicians and patients as treatment can be maintained without the concern of rising cost increments."
The minimal dose escalation observed in patients treated with etanercept may be due to its molecular structure which makes the development of neutralizing antibodies less likely than in patients treated with adalimumab and infliximab.2,3,4,5,6 Recent studies have shown that physicians find that efficacy with some biological therapies diminishes or wears off over a period of time and hence may lead to the need for dose escalation and subsequent increased costs of treatment.2,3,4 This may be partially due to the development of neutralizing antibodies.
To assist in the analysis of current clinical practice, an investigator survey was conducted to assess restriction on dose adjustment and the preferred strategy when an inadequate clinical response was observed. Two in five investigators felt restrictions prevented them from increasing the dose or frequency of anti-TNF agents. Despite these restrictions a similar pattern of dose escalation was observed in these centres compared to the overall dose escalation results. Adding, or increasing the dose of a DMARD, was used in some countries when restrictions prohibited the dose escalation of ATAs.1
In conclusion the DART study investigators report that the results suggest that patients receiving the monoclonal antibodies to TNF (infliximab and adalimumab), have a significantly higher rate of dose escalation than patients receiving the soluble TNF receptor etanercept, even in a restrictive budgetary environment and despite lower initial or concurrent DMARD use in etanercept patients.
About Enbrel7
ENBREL is a fully human soluble tumour necrosis factor (TNF) receptor antagonist. ENBREL was first approved in 1998 for moderate to rheumatoid arthritis and has since been used in nearly 500,000 patients worldwide across indications.
ENBREL in the EU is approved for the following indications:
Rheumatoid arthritis
Enbrel in combination with methotrexate is indicated for the treatment of moderate to severe active rheumatoid arthritis in adults when the response to disease-modifying antirheumatic drugs, including methotrexate (unless contraindicated), has been inadequate. Enbrel can be given as monotherapy in case of intolerance to methotrexate or when continued treatment with methotrexate is inappropriate. Enbrel is also indicated in the treatment of severe, active and progressive rheumatoid arthritis in adults not previously treated with methotrexate. Enbrel, alone or in combination with methotrexate, has been shown to reduce the rate of progression of joint damage as measured by X-ray and to improve physical function.
Polyarticular juvenile idiopathic arthritis
Treatment of active polyarticular juvenile idiopathic arthritis in children and adolescents aged 4 to 17 years who have had an inadequate response to, or who have proved intolerant of, methotrexate. Enbrel has not been studied in children aged less than 4 years.
Psoriatic arthritis
Treatment of active and progressive psoriatic arthritis in adults when the response to previous disease-modifying antirheumatic drug therapy has been inadequate. Enbrel has been shown to improve physical function in patients with psoriatic arthritis, and to reduce the rate of progression of peripheral joint damage as measured by X-ray in patients with polyarticular symmetrical subtypes of the disease.
Ankylosing spondylitis
Treatment of adults with severe active ankylosing spondylitis who have had an inadequate response to conventional therapy.
Plaque psoriasis
Treatment of adults with moderate to severe plaque psoriasis who failed to respond to, or who have a contraindication to, or are intolerant to other systemic therapy including cyclosporine, methotrexate or PUVA
Dart* Study Details1
The DART (Anti-TNF Drug utilization and dosing patterns Assessment: a Retrospective observational study of subjects Treated for rheumatoid arthritis) study is a retrospective observational study involving 739 patients in 44 European centres treated with monoclonal antibodies to TNF-?± or soluble TNF-?± receptor over >12 month period. The study was designed to assess potential dose escalation and other associated treatment costs on routine clinical practice. Eligible subjects were required to be continuously treated with prescribed anti-TNF agent (ATA) for ?‰?12 months and have no concurrent diagnosis of any other TNF-mediated conditions.
About Wyeth
Wyeth is one of the world's largest research-based pharmaceutical and health care products companies. It is a leader in the discovery, development, manufacturing, and marketing of prescription drugs and over-the-counter medications. It is also a global leader in vaccines, biotechnology and animal health care. wyeth
v
References
1. Moots R et al. Patterns of dose escalation and DMARD intensification in 739 patients with rheumatoid arthritis (RA) treated with anti-TNF agents (ATAs): Results from the DART study. Presented at the British Society of Rheumatology annual meeting, 24 April 2008, Liverpool, UK; Abstract 418
2. Bartelds GM et al. Clinical response to adalimumab: relationship to anti-adalimumab antibodies and serum adalimumab concentrations in rheumatoid arthritis. Ann Rheum Dis 2007 Jul;66(7):921-6
3. van der Laken CJ et al. Imaging and serum analysis of immune complex formation of radiolabelled infliximab and anti-infliximab in responders and non-responders to therapy for rheumatoid arthritis. Ann Rheum Dis. 2007 Feb;66(2):253-6
4. Wolbink GJ et al. Relationship between serum trough infliximab levels, pretreatment C reactive protein levels, and clinical response to infliximab treatment in patients with rheumatoid arthritis. Ann Rheum Dis. 2005 May;64(5):704-7
5. Remicade® (infliximab) EMEA SPC: Last accessed 16 April 2008
6. Humira® (adalimumab) EMEA SPC. . Last accessed 16 April 2008
7. Enbrel EMEA SPC Last accessed 14 April 2008
wyeth
View drug information on Enbrel; Humira; Remicade.
The DART* study assessed current clinical practice in the treatment of rheumatoid arthritis patients by comparing potential dose escalation in three selected ATAs and their associated costs of treatment.1 The results of the 44 European centre study showed that the dose escalation to maintain clinical response was less than 1 per cent with etanercept compared to 8 per cent with adalimumab and 29 per cent with infliximab in the first 12 months. In those study centres where there were no restrictions to prescribing ATAs, the results showed a 2 per cent dose escalation with etanercept versus 11 per cent and 35 per cent respectively, indicating that associated cost increments were negligible with etanercept.1
"The results of the DART study add to the body of evidence that etanercept achieves sustained efficacy without the need for dose escalation in 99 per cent of patients studied and thus demonstrates a cost effective treatment option for patients with rheumatoid arthritis over both the short and long term," said Professor Robert Moots, Professor of Rheumatology, University of Liverpool, Liverpool, United Kingdom and DART study investigator. "The current perception of biological therapy for inflammatory conditions such as rheumatoid arthritis is that it can be costly, however if the long term outlook and patient quality of life is taken into consideration, biologics such as etanercept are extremely cost effective. This is important both for physicians and patients as treatment can be maintained without the concern of rising cost increments."
The minimal dose escalation observed in patients treated with etanercept may be due to its molecular structure which makes the development of neutralizing antibodies less likely than in patients treated with adalimumab and infliximab.2,3,4,5,6 Recent studies have shown that physicians find that efficacy with some biological therapies diminishes or wears off over a period of time and hence may lead to the need for dose escalation and subsequent increased costs of treatment.2,3,4 This may be partially due to the development of neutralizing antibodies.
To assist in the analysis of current clinical practice, an investigator survey was conducted to assess restriction on dose adjustment and the preferred strategy when an inadequate clinical response was observed. Two in five investigators felt restrictions prevented them from increasing the dose or frequency of anti-TNF agents. Despite these restrictions a similar pattern of dose escalation was observed in these centres compared to the overall dose escalation results. Adding, or increasing the dose of a DMARD, was used in some countries when restrictions prohibited the dose escalation of ATAs.1
In conclusion the DART study investigators report that the results suggest that patients receiving the monoclonal antibodies to TNF (infliximab and adalimumab), have a significantly higher rate of dose escalation than patients receiving the soluble TNF receptor etanercept, even in a restrictive budgetary environment and despite lower initial or concurrent DMARD use in etanercept patients.
About Enbrel7
ENBREL is a fully human soluble tumour necrosis factor (TNF) receptor antagonist. ENBREL was first approved in 1998 for moderate to rheumatoid arthritis and has since been used in nearly 500,000 patients worldwide across indications.
ENBREL in the EU is approved for the following indications:
Rheumatoid arthritis
Enbrel in combination with methotrexate is indicated for the treatment of moderate to severe active rheumatoid arthritis in adults when the response to disease-modifying antirheumatic drugs, including methotrexate (unless contraindicated), has been inadequate. Enbrel can be given as monotherapy in case of intolerance to methotrexate or when continued treatment with methotrexate is inappropriate. Enbrel is also indicated in the treatment of severe, active and progressive rheumatoid arthritis in adults not previously treated with methotrexate. Enbrel, alone or in combination with methotrexate, has been shown to reduce the rate of progression of joint damage as measured by X-ray and to improve physical function.
Polyarticular juvenile idiopathic arthritis
Treatment of active polyarticular juvenile idiopathic arthritis in children and adolescents aged 4 to 17 years who have had an inadequate response to, or who have proved intolerant of, methotrexate. Enbrel has not been studied in children aged less than 4 years.
Psoriatic arthritis
Treatment of active and progressive psoriatic arthritis in adults when the response to previous disease-modifying antirheumatic drug therapy has been inadequate. Enbrel has been shown to improve physical function in patients with psoriatic arthritis, and to reduce the rate of progression of peripheral joint damage as measured by X-ray in patients with polyarticular symmetrical subtypes of the disease.
Ankylosing spondylitis
Treatment of adults with severe active ankylosing spondylitis who have had an inadequate response to conventional therapy.
Plaque psoriasis
Treatment of adults with moderate to severe plaque psoriasis who failed to respond to, or who have a contraindication to, or are intolerant to other systemic therapy including cyclosporine, methotrexate or PUVA
Dart* Study Details1
The DART (Anti-TNF Drug utilization and dosing patterns Assessment: a Retrospective observational study of subjects Treated for rheumatoid arthritis) study is a retrospective observational study involving 739 patients in 44 European centres treated with monoclonal antibodies to TNF-?± or soluble TNF-?± receptor over >12 month period. The study was designed to assess potential dose escalation and other associated treatment costs on routine clinical practice. Eligible subjects were required to be continuously treated with prescribed anti-TNF agent (ATA) for ?‰?12 months and have no concurrent diagnosis of any other TNF-mediated conditions.
About Wyeth
Wyeth is one of the world's largest research-based pharmaceutical and health care products companies. It is a leader in the discovery, development, manufacturing, and marketing of prescription drugs and over-the-counter medications. It is also a global leader in vaccines, biotechnology and animal health care. wyeth
v
References
1. Moots R et al. Patterns of dose escalation and DMARD intensification in 739 patients with rheumatoid arthritis (RA) treated with anti-TNF agents (ATAs): Results from the DART study. Presented at the British Society of Rheumatology annual meeting, 24 April 2008, Liverpool, UK; Abstract 418
2. Bartelds GM et al. Clinical response to adalimumab: relationship to anti-adalimumab antibodies and serum adalimumab concentrations in rheumatoid arthritis. Ann Rheum Dis 2007 Jul;66(7):921-6
3. van der Laken CJ et al. Imaging and serum analysis of immune complex formation of radiolabelled infliximab and anti-infliximab in responders and non-responders to therapy for rheumatoid arthritis. Ann Rheum Dis. 2007 Feb;66(2):253-6
4. Wolbink GJ et al. Relationship between serum trough infliximab levels, pretreatment C reactive protein levels, and clinical response to infliximab treatment in patients with rheumatoid arthritis. Ann Rheum Dis. 2005 May;64(5):704-7
5. Remicade® (infliximab) EMEA SPC: Last accessed 16 April 2008
6. Humira® (adalimumab) EMEA SPC. . Last accessed 16 April 2008
7. Enbrel EMEA SPC Last accessed 14 April 2008
wyeth
View drug information on Enbrel; Humira; Remicade.
четверг, 28 апреля 2011 г.
Pharming Receives Agreement On Paediatric Investigation Plan For Rhucin(R) From The EMEA Paediatric Committee
Biotech company Pharming Group NV ("Pharming" or "the Company") (NYSE Euronext: PHARM) today announced that the Paediatric Committee (PDCO) of the European Medicines Agency (EMEA) has adopted an opinion agreeing the paediatric investigation plan (PIP) for Rhucin® (recombinant human C1 inhibitor) in the therapeutic area of immunology-rheumatology transplantation.
"Agreement of the PIP represents a key milestone in Pharming's regulatory plans for the September 2009 submission of the Rhucin marketing authorisation application," said Dr. Bruno Giannetti, COO of Pharming.
According to the EC Regulation 1901/2006 of 12 December 2006, pharmaceutical companies that submit an application for a marketing authorisation for a medicinal product (MAA) in the EU, have to include an approved PIP as part of the regulatory submission.
Source
Pharming Group NV
"Agreement of the PIP represents a key milestone in Pharming's regulatory plans for the September 2009 submission of the Rhucin marketing authorisation application," said Dr. Bruno Giannetti, COO of Pharming.
According to the EC Regulation 1901/2006 of 12 December 2006, pharmaceutical companies that submit an application for a marketing authorisation for a medicinal product (MAA) in the EU, have to include an approved PIP as part of the regulatory submission.
Source
Pharming Group NV
среда, 27 апреля 2011 г.
Phase III Study Showed Two Years Of ACTEMRA(R) (tocilizumab) Inhibited Progression Of Joint Damage And Improved Disease Remission
Genentech, Inc., a wholly-owned member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), announced two-year results from a Phase III study, which showed that people with rheumatoid arthritis (RA) who received either a 4 mg/kg or 8 mg/kg dose of ACTEMRA® (tocilizumab), in combination with methotrexate, had no progression of joint damage, (75 and 83 percent, respectively, as assessed by radiograph) compared with people who received methotrexate alone (66 percent). The overall safety profile of ACTEMRA was consistent across all global clinical studies. The study, known as LITHE, will be featured as an oral presentation during the American College of Rheumatology (ACR) Annual Scientific Meeting along with results from two additional studies evaluating the long-term use of ACTEMRA in people with RA.
The LITHE study also showed that people who received either dose of ACTEMRA plus methotrexate showed significant improvement in physical function, compared with people who received methotrexate plus placebo, as measured by the mean area under the curve (AUC) of the Health Assessment Questionnaire Disability Index (HAQ-DI)i change from baseline. In addition, 65 percent of people who received ACTEMRA (8 mg/kg) plus methotrexate for two years had their disease go into remission compared with 48 percent of people treated for just one year. In this study, remission was defined by achieving a disease activity score (called DAS28) of less than 2.6ii. DAS28 is a commonly used tool that assesses a variety of measures, including swollen and tender joints at multiple time points.
"Two primary goals in treating RA are keeping the disease in remission for as long as possible and reducing the amount of joint damage that occurs," said Hal Barron, M.D., executive vice president, Global Development and chief medical officer, Genentech. "This study showed that ACTEMRA both improved physical function and delayed progression of joint damage in people with moderate to severe RA and importantly, that benefit was sustained for two years."
Pooled Long-Term Efficacy and Safety Analyses
Pooled data from three Phase III pivotal studies, including LITHE, and two long-term extension studies, showed that at week 48 and beyond more than one third of people who had previously failed disease modifying anti-rheumatic drugs (DMARDs) and received either dose of ACTEMRA achieved disease remission, as defined by a disease activity score (DAS28) of less than 2.6, regardless of prior treatment history or disease duration.
An additional analysis presented at the meeting showed that no new safety signals have emerged with people who received ACTEMRA over an average duration of nearly two and a half years, and the overall safety profile of ACTEMRA was consistent with previous experience.
About the Studies
LITHE (TociLIzumab Safety and THE Prevention of Structural Joint Damage) was a three-arm, randomized, double-blind, placebo-controlled study in the first year with people receiving either 4 mg/kg or 8 mg/kg of ACTEMRA, and either a double-blind or an open-label study with the majority of people receiving ACTEMRA 8 mg/kg in the second year. The study was designed to evaluate the safety and efficacy profile of ACTEMRA plus methotrexate compared with placebo plus methotrexate for the prevention of structural joint damage and improvement in physical function over two years in people with RA.
The study evaluated nearly 1,200 people with RA at 137 sites in 15 countries, including the United States. The overall safety profile of ACTEMRA was consistent across all global clinical studies. The most common individual serious adverse events (SAEs) were serious infections such as pneumonia, cellulitis, gastroenteritis and bronchitis. The most frequent individual adverse events (AEs) were upper respiratory infection, bronchitis, urinary tract infection, hypertension, nasopharyngitis and increased transaminases.
The pooled long-term efficacy and safety analyses included all participants from five pivotal Phase III, randomized, controlled studies (OPTION, TOWARD, RADIATE, AMBITION, and LITHE one year) and two long-term extension studies (GROWTH95 and GROWTH96) to examine the safety and efficacy profile of ACTEMRA across different RA populations: DMARD-IR (inadequate response), anti-TNF-IR and monotherapy.
The analyses each evaluated approximately 4,000 people with RA, throughout the world. The overall safety profile of ACTEMRA was consistent across all global clinical studies. The SAEs reported most frequently in the ACTEMRA arms of the studies were pneumonia, and the most common AEs reported were upper respiratory tract infections.
About ACTEMRA® (tocilizumab)
ACTEMRA is the first humanized interleukin-6 (IL-6) receptor-inhibiting monoclonal antibody being studied for the treatment of RA. Studies demonstrate that reducing the activity of IL-6, one of several key cytokines involved in the inflammatory process, relieves both inflammation of the joints and certain systemic effects of RA. The extensive ACTEMRA clinical development program includes five Phase III clinical studies and has enrolled more than 4,000 people with RA in 41 countries, including the United States. All five Phase III studies are completed and have reported meeting their primary endpoints. ACTEMRA is currently being reviewed by the U.S. Food and Drug Administration (FDA).
ACTEMRA is part of a co-development agreement with Chugai Pharmaceutical Co. In June 2005, ACTEMRA was launched by Chugai in Japan as a therapy for Castleman's disease. In April 2008, additional indications for RA, juvenile idiopathic arthritis and systemic-onset juvenile idiopathic arthritis were also approved in Japan. ACTEMRA is known as RoACTEMRA in the European Union, and is approved in several other countries, including India, Brazil, Switzerland and Australia, in combination with methotrexate for the treatment of adult patients with moderate to severe RA who have either responded inadequately to, or who were intolerant to, previous therapy with one or more disease modifying anti-rheumatic drugs or tumor necrosis factor antagonists. In these patients, RoACTEMRA can be given as monotherapy in cases of intolerance to methotrexate or where continued treatment with methotrexate is inappropriate.
The SAEs reported in ACTEMRA clinical studies include serious infections, gastrointestinal perforations and hypersensitivity reactions including anaphylaxis. The most common AEs reported in clinical studies were upper respiratory tract infection, nasopharyngitis, headache, hypertension and increased ALT. Increases in liver enzymes (ALT and AST) were seen in patients; these increases were generally mild and reversible, with no evidence of hepatic injuries. Laboratory changes, including increases in lipids (total cholesterol, LDL, HDL and triglycerides) and decreases in neutrophils and platelets, were seen in patients without association with clinical outcomes. Treatments that suppress the immune system, such as ACTEMRA, may cause an increase in the risk of malignancies.
About IL-6
IL-6 is a common protein found in all joints in the body and is a natural substance that can raise inflammation. Everyone has IL-6 in their body, but people with RA may have too much. If approved by the FDA, ACTEMRA will be the first and only medication to specifically target IL-6 in patients with RA.
About Rheumatoid Arthritis
Rheumatoid arthritis is a progressive, systemic autoimmune disease characterized by inflammation of the membrane lining in the joints. This inflammation causes a loss of joint shape and function, resulting in pain, stiffness and swelling, ultimately leading to irreversible joint destruction and disability. Characteristics of RA include redness, swelling, pain and movement limitation around joints of the hands, feet, elbows, knees and neck that leads to loss of function. In addition, the systemic symptoms of RA include fatigue, decreased hemoglobin, osteoporosis and may contribute to shortening life expectancy by affecting major organ systems. After 10 years, less than 50 percent of patients can continue to work or function normally on a daily basis. RA affects more than 21 million people worldwide with approximately 1.3 million adults affected in the United States.
i The Health Assessment Questionnaire Disability Index (HAQ-DI) is a 20-item questionnaire that asks about physical functioning within eight categories (dressing and grooming, arising, eating, walking, hygiene, reach, grip and daily activities). The ability to perform each category is measured on a scale 0 to 3 (0 = no difficulty, 1 = some difficulty, 2 = much difficulty or with assistance, and 3 = unable).
ii The Disease Activity Score (DAS)28 is a combined index that measures disease activity in patients with RA. It combines information from 28 tender and swollen joints (range 0-28), erythrocyte sedimentation rate, and a general health assessment on a visual analog scale. The level of disease activity is interpreted as low (DAS28?‰¤3.2), moderate (3.25.1). DAS28
The LITHE study also showed that people who received either dose of ACTEMRA plus methotrexate showed significant improvement in physical function, compared with people who received methotrexate plus placebo, as measured by the mean area under the curve (AUC) of the Health Assessment Questionnaire Disability Index (HAQ-DI)i change from baseline. In addition, 65 percent of people who received ACTEMRA (8 mg/kg) plus methotrexate for two years had their disease go into remission compared with 48 percent of people treated for just one year. In this study, remission was defined by achieving a disease activity score (called DAS28) of less than 2.6ii. DAS28 is a commonly used tool that assesses a variety of measures, including swollen and tender joints at multiple time points.
"Two primary goals in treating RA are keeping the disease in remission for as long as possible and reducing the amount of joint damage that occurs," said Hal Barron, M.D., executive vice president, Global Development and chief medical officer, Genentech. "This study showed that ACTEMRA both improved physical function and delayed progression of joint damage in people with moderate to severe RA and importantly, that benefit was sustained for two years."
Pooled Long-Term Efficacy and Safety Analyses
Pooled data from three Phase III pivotal studies, including LITHE, and two long-term extension studies, showed that at week 48 and beyond more than one third of people who had previously failed disease modifying anti-rheumatic drugs (DMARDs) and received either dose of ACTEMRA achieved disease remission, as defined by a disease activity score (DAS28) of less than 2.6, regardless of prior treatment history or disease duration.
An additional analysis presented at the meeting showed that no new safety signals have emerged with people who received ACTEMRA over an average duration of nearly two and a half years, and the overall safety profile of ACTEMRA was consistent with previous experience.
About the Studies
LITHE (TociLIzumab Safety and THE Prevention of Structural Joint Damage) was a three-arm, randomized, double-blind, placebo-controlled study in the first year with people receiving either 4 mg/kg or 8 mg/kg of ACTEMRA, and either a double-blind or an open-label study with the majority of people receiving ACTEMRA 8 mg/kg in the second year. The study was designed to evaluate the safety and efficacy profile of ACTEMRA plus methotrexate compared with placebo plus methotrexate for the prevention of structural joint damage and improvement in physical function over two years in people with RA.
The study evaluated nearly 1,200 people with RA at 137 sites in 15 countries, including the United States. The overall safety profile of ACTEMRA was consistent across all global clinical studies. The most common individual serious adverse events (SAEs) were serious infections such as pneumonia, cellulitis, gastroenteritis and bronchitis. The most frequent individual adverse events (AEs) were upper respiratory infection, bronchitis, urinary tract infection, hypertension, nasopharyngitis and increased transaminases.
The pooled long-term efficacy and safety analyses included all participants from five pivotal Phase III, randomized, controlled studies (OPTION, TOWARD, RADIATE, AMBITION, and LITHE one year) and two long-term extension studies (GROWTH95 and GROWTH96) to examine the safety and efficacy profile of ACTEMRA across different RA populations: DMARD-IR (inadequate response), anti-TNF-IR and monotherapy.
The analyses each evaluated approximately 4,000 people with RA, throughout the world. The overall safety profile of ACTEMRA was consistent across all global clinical studies. The SAEs reported most frequently in the ACTEMRA arms of the studies were pneumonia, and the most common AEs reported were upper respiratory tract infections.
About ACTEMRA® (tocilizumab)
ACTEMRA is the first humanized interleukin-6 (IL-6) receptor-inhibiting monoclonal antibody being studied for the treatment of RA. Studies demonstrate that reducing the activity of IL-6, one of several key cytokines involved in the inflammatory process, relieves both inflammation of the joints and certain systemic effects of RA. The extensive ACTEMRA clinical development program includes five Phase III clinical studies and has enrolled more than 4,000 people with RA in 41 countries, including the United States. All five Phase III studies are completed and have reported meeting their primary endpoints. ACTEMRA is currently being reviewed by the U.S. Food and Drug Administration (FDA).
ACTEMRA is part of a co-development agreement with Chugai Pharmaceutical Co. In June 2005, ACTEMRA was launched by Chugai in Japan as a therapy for Castleman's disease. In April 2008, additional indications for RA, juvenile idiopathic arthritis and systemic-onset juvenile idiopathic arthritis were also approved in Japan. ACTEMRA is known as RoACTEMRA in the European Union, and is approved in several other countries, including India, Brazil, Switzerland and Australia, in combination with methotrexate for the treatment of adult patients with moderate to severe RA who have either responded inadequately to, or who were intolerant to, previous therapy with one or more disease modifying anti-rheumatic drugs or tumor necrosis factor antagonists. In these patients, RoACTEMRA can be given as monotherapy in cases of intolerance to methotrexate or where continued treatment with methotrexate is inappropriate.
The SAEs reported in ACTEMRA clinical studies include serious infections, gastrointestinal perforations and hypersensitivity reactions including anaphylaxis. The most common AEs reported in clinical studies were upper respiratory tract infection, nasopharyngitis, headache, hypertension and increased ALT. Increases in liver enzymes (ALT and AST) were seen in patients; these increases were generally mild and reversible, with no evidence of hepatic injuries. Laboratory changes, including increases in lipids (total cholesterol, LDL, HDL and triglycerides) and decreases in neutrophils and platelets, were seen in patients without association with clinical outcomes. Treatments that suppress the immune system, such as ACTEMRA, may cause an increase in the risk of malignancies.
About IL-6
IL-6 is a common protein found in all joints in the body and is a natural substance that can raise inflammation. Everyone has IL-6 in their body, but people with RA may have too much. If approved by the FDA, ACTEMRA will be the first and only medication to specifically target IL-6 in patients with RA.
About Rheumatoid Arthritis
Rheumatoid arthritis is a progressive, systemic autoimmune disease characterized by inflammation of the membrane lining in the joints. This inflammation causes a loss of joint shape and function, resulting in pain, stiffness and swelling, ultimately leading to irreversible joint destruction and disability. Characteristics of RA include redness, swelling, pain and movement limitation around joints of the hands, feet, elbows, knees and neck that leads to loss of function. In addition, the systemic symptoms of RA include fatigue, decreased hemoglobin, osteoporosis and may contribute to shortening life expectancy by affecting major organ systems. After 10 years, less than 50 percent of patients can continue to work or function normally on a daily basis. RA affects more than 21 million people worldwide with approximately 1.3 million adults affected in the United States.
i The Health Assessment Questionnaire Disability Index (HAQ-DI) is a 20-item questionnaire that asks about physical functioning within eight categories (dressing and grooming, arising, eating, walking, hygiene, reach, grip and daily activities). The ability to perform each category is measured on a scale 0 to 3 (0 = no difficulty, 1 = some difficulty, 2 = much difficulty or with assistance, and 3 = unable).
ii The Disease Activity Score (DAS)28 is a combined index that measures disease activity in patients with RA. It combines information from 28 tender and swollen joints (range 0-28), erythrocyte sedimentation rate, and a general health assessment on a visual analog scale. The level of disease activity is interpreted as low (DAS28?‰¤3.2), moderate (3.25.1). DAS28
вторник, 26 апреля 2011 г.
New drug helps improve mobility in children with arthritis
A new potential treatment for a rare and severe form of arthritis in children may improve their mobility and relieve
fever. Paediatric rheumatologist, Professor Patricia Woo presented the results of a preliminary trial today (Friday 10 June)
at the Annual European Congress of Rheumatology in Vienna.
Systemic juvenile idiopathic arthritis (sJIA) affects around 600 children in the UK. As well as swollen, painful joints, the
child has rashes, a swingeing, high fever and become very unwell. Growth is often affected. "There are lots of problems that
we cannot control well or treat," said Professor Woo from Great Ormond Street Hospital in London, UK.
Research carried out by Professor Woo and other investigators had previously identified a protein, called interleukin 6
(IL-6), which provokes inflammation, especially in sJIA. A potential new drug, Tocilizumab, previously known as MRA, blocks
its action.
In the phase II trial to investigate the safety and efficacy of MRA, 18 children from UK and France with sJIA were treated
with different doses of MRA. There were nine in each age group, two to five and six - 18 years old and their disease had not
responded to other treatments. Each child was given one dose of MRA by intravenous injection. They were monitored regularly
throughout the following two months.
"There was a significant improvement in all the children, particularly those who received a higher dose of MRA," said
Professor Woo. "Their fever settled down and they were more mobile." Inevitably, as the effects of one dose wore off, the
children did relapse but the beneficial effects last for two to six weeks. There were no significant safety concerns.
"This is only a phase II trial and it is much too soon to draw conclusions, but it is very encouraging to see that a single
dose can produce such dramatic clinical responses," she said. An international study with Tocilizumab in children suffering
form sJIA is currently in preparation. A similar trial is ongoing in Japan.
Abstract no. 086
Reference URL
eular
fever. Paediatric rheumatologist, Professor Patricia Woo presented the results of a preliminary trial today (Friday 10 June)
at the Annual European Congress of Rheumatology in Vienna.
Systemic juvenile idiopathic arthritis (sJIA) affects around 600 children in the UK. As well as swollen, painful joints, the
child has rashes, a swingeing, high fever and become very unwell. Growth is often affected. "There are lots of problems that
we cannot control well or treat," said Professor Woo from Great Ormond Street Hospital in London, UK.
Research carried out by Professor Woo and other investigators had previously identified a protein, called interleukin 6
(IL-6), which provokes inflammation, especially in sJIA. A potential new drug, Tocilizumab, previously known as MRA, blocks
its action.
In the phase II trial to investigate the safety and efficacy of MRA, 18 children from UK and France with sJIA were treated
with different doses of MRA. There were nine in each age group, two to five and six - 18 years old and their disease had not
responded to other treatments. Each child was given one dose of MRA by intravenous injection. They were monitored regularly
throughout the following two months.
"There was a significant improvement in all the children, particularly those who received a higher dose of MRA," said
Professor Woo. "Their fever settled down and they were more mobile." Inevitably, as the effects of one dose wore off, the
children did relapse but the beneficial effects last for two to six weeks. There were no significant safety concerns.
"This is only a phase II trial and it is much too soon to draw conclusions, but it is very encouraging to see that a single
dose can produce such dramatic clinical responses," she said. An international study with Tocilizumab in children suffering
form sJIA is currently in preparation. A similar trial is ongoing in Japan.
Abstract no. 086
Reference URL
eular
понедельник, 25 апреля 2011 г.
Rheumatoid Arthritis Breakthrough - Plos Biology
Rheumatoid arthritis is a painful, inflammatory type of arthritis that occurs when the body's immune system attacks itself. A new paper, published in this week's issue of PLoS Biology, reports a breakthrough in the understanding of how autoimmune responses can be controlled, offering a
promising new strategy for therapy development for rheumatoid arthritis.
Normally, immune cells develop to recognise foreign material - antigens; including bacteria - so that they can activate a response against them.
Immune cells that would respond to 'self' and therefore attack the body's own cells are usually destroyed during development. If any persist, they are held in check by special regulatory cells that provide a sort of autoimmune checkpoint. A key player in these regulatory cells is a molecule
called Foxp3. People who lack or have mutated versions of the Foxp3 gene lack or have dysfunctional immune regulation, which causes dramatic
autoimmune disease.
Scientists at the Medical Research Council's Laboratory of Molecular Biology in Cambridge, and funded by the Arthritis Research Campaign, have
genetically engineered a drug-inducible form of Foxp3. Using this, scientists can 'switch' developing immune cells into regulatory cells that are
then capable of suppressing the immune response.
Dr. Alexander Betz, Group Leader at the MRC laboratory, explains: "We have generated a modified form of Foxp3 which can be introduced into immune
cells using genetic engineering techniques and then activated by a simple injection. When administered to and activated in animal models of arthritis,
the modified cells inhibit or even reverse the disease process."
Further work is now aimed at elucidating the detailed molecular mechanisms involved in Foxp3 function, and transferring the experimental approach to
human cells.
"First, we will develop a human Foxp3 factor and then assess its function in human arthritis models," said Dr Betz. "To be viable as a
therapeutic option, the regulatory cells must fulfill certain criteria; they must be tissue matched to the patient for compatibility; they must only
block the targeted disease and not the whole body immune response; and they have to home correctly to their target tissue. Establishing these criteria
will be the key focus of our research.
"If Foxp3 functions as a key developmental switch in human immune cells, there is potential for a new avenue of therapy development that could
transform arthritis treatment is substantial," he added.
Andersen KG, Butcher T, Betz AG (2008)
Specific immunosuppression with inducible Foxp3-transduced polyclonal T cells.
PLoS Biol 6(11): e276. doi:10.1371/journal.pbio.0060276
Click here to view article online
PLoS Biology
PLoS Biology (eISSN-1545-7885; ISSN-1544-9173) is an open-access, peer-reviewed general biology journal published by the Public Library of Science (PLoS), a nonprofit organization of scientists and physicians committed to making the world's scientific and medical literature a public resource. New articles are published online weekly; issues are published monthly.
biology.plosjournals
Public Library of Science
185 Berry Street, Suite 3100
San Francisco, CA 94107
USA
plos
promising new strategy for therapy development for rheumatoid arthritis.
Normally, immune cells develop to recognise foreign material - antigens; including bacteria - so that they can activate a response against them.
Immune cells that would respond to 'self' and therefore attack the body's own cells are usually destroyed during development. If any persist, they are held in check by special regulatory cells that provide a sort of autoimmune checkpoint. A key player in these regulatory cells is a molecule
called Foxp3. People who lack or have mutated versions of the Foxp3 gene lack or have dysfunctional immune regulation, which causes dramatic
autoimmune disease.
Scientists at the Medical Research Council's Laboratory of Molecular Biology in Cambridge, and funded by the Arthritis Research Campaign, have
genetically engineered a drug-inducible form of Foxp3. Using this, scientists can 'switch' developing immune cells into regulatory cells that are
then capable of suppressing the immune response.
Dr. Alexander Betz, Group Leader at the MRC laboratory, explains: "We have generated a modified form of Foxp3 which can be introduced into immune
cells using genetic engineering techniques and then activated by a simple injection. When administered to and activated in animal models of arthritis,
the modified cells inhibit or even reverse the disease process."
Further work is now aimed at elucidating the detailed molecular mechanisms involved in Foxp3 function, and transferring the experimental approach to
human cells.
"First, we will develop a human Foxp3 factor and then assess its function in human arthritis models," said Dr Betz. "To be viable as a
therapeutic option, the regulatory cells must fulfill certain criteria; they must be tissue matched to the patient for compatibility; they must only
block the targeted disease and not the whole body immune response; and they have to home correctly to their target tissue. Establishing these criteria
will be the key focus of our research.
"If Foxp3 functions as a key developmental switch in human immune cells, there is potential for a new avenue of therapy development that could
transform arthritis treatment is substantial," he added.
Andersen KG, Butcher T, Betz AG (2008)
Specific immunosuppression with inducible Foxp3-transduced polyclonal T cells.
PLoS Biol 6(11): e276. doi:10.1371/journal.pbio.0060276
Click here to view article online
PLoS Biology
PLoS Biology (eISSN-1545-7885; ISSN-1544-9173) is an open-access, peer-reviewed general biology journal published by the Public Library of Science (PLoS), a nonprofit organization of scientists and physicians committed to making the world's scientific and medical literature a public resource. New articles are published online weekly; issues are published monthly.
biology.plosjournals
Public Library of Science
185 Berry Street, Suite 3100
San Francisco, CA 94107
USA
plos
воскресенье, 24 апреля 2011 г.
Cartilage Repair Gel Under Development, Which Will Improve Quality Of Life For People Suffering With Medical Joint Trouble
The University of Bradford's School of Engineering, Design and Technology and Advanced Gel Technology Ltd (AGT), a University spin-out company, are developing a cartilage repair gel to improve the quality of life for people suffering with medical joint trouble such as osteoarthritis.
The ??135,000 project, funded by AGT and partly by Yorkshire Forward began three years ago, and whilst the gel is not at clinical trial stage yet, the University and AGT are confident that it can help hundreds of people.
Unlike most other parts of the body, cartilage cannot be repaired easily meaning that most joint sufferers need to undergo major invasive surgery to replace the joint.
Joint replacements last around 10-15 years and revising them is difficult, which means surgery is generally only recommended for age groups where the replacement will last them the rest of their life.
Treating patients who need surgery with the alternative hydrogel therapy that the University and AGT are working on would mean a much less invasive procedure, which could hold off joint replacement surgery for at least five years.
Currently the University and AGT are looking at joints which have suffered trauma from a car accident or a sport injury where the cartilage has been torn or has a hole in it. The idea behind the repair gel is that they would drill a bigger hole into the tear and fill it with the gel to substitute the original cartilage and stop the pain caused by the bones rubbing against each other.
Dr Pete Twigg, Lead Researcher of the Cartilage Repair Project at the University of Bradford, said: "The potential for improved quality of life is huge. The number of people suffering from cartilage problems is increasing every year.
"Total joint replacement is very successful, but may not be appropriate for younger, more active people. They are often encouraged to put off surgery until the pain is disabling, but a conservative replacement treatment could relieve pain and restore function at a much earlier stage."
The hydrogel treatment would be a very simple procedure and eventually could be something carried out as day surgery, where a needle could be inserted through the skin into the affected area.
Notes:
AGT Sciences' advanced polymer hydrogel represents a unique and flexible technological platform with an extremely wide scope of controllable properties.
Hydrogel is made up almost entirely of water, yet can thicken to produce a substance 100-1000 times stronger than any other gel of its kind.
This is because it is composed of two very long elastic-like molecules that form strong covalent bonds with each other to form a 3D network, like a cage, that holds the water. By adjusting the number of bonds, the physico-chemical properties of the gel can be manipulated to make it thick, thin or sticky. The gel also has the capability to hold molecules of other substances, whether water soluble or water insoluble (e.g. oil).
For more information about AGT visit agtsciences
Source:
Emma Banks
University of Bradford
The ??135,000 project, funded by AGT and partly by Yorkshire Forward began three years ago, and whilst the gel is not at clinical trial stage yet, the University and AGT are confident that it can help hundreds of people.
Unlike most other parts of the body, cartilage cannot be repaired easily meaning that most joint sufferers need to undergo major invasive surgery to replace the joint.
Joint replacements last around 10-15 years and revising them is difficult, which means surgery is generally only recommended for age groups where the replacement will last them the rest of their life.
Treating patients who need surgery with the alternative hydrogel therapy that the University and AGT are working on would mean a much less invasive procedure, which could hold off joint replacement surgery for at least five years.
Currently the University and AGT are looking at joints which have suffered trauma from a car accident or a sport injury where the cartilage has been torn or has a hole in it. The idea behind the repair gel is that they would drill a bigger hole into the tear and fill it with the gel to substitute the original cartilage and stop the pain caused by the bones rubbing against each other.
Dr Pete Twigg, Lead Researcher of the Cartilage Repair Project at the University of Bradford, said: "The potential for improved quality of life is huge. The number of people suffering from cartilage problems is increasing every year.
"Total joint replacement is very successful, but may not be appropriate for younger, more active people. They are often encouraged to put off surgery until the pain is disabling, but a conservative replacement treatment could relieve pain and restore function at a much earlier stage."
The hydrogel treatment would be a very simple procedure and eventually could be something carried out as day surgery, where a needle could be inserted through the skin into the affected area.
Notes:
AGT Sciences' advanced polymer hydrogel represents a unique and flexible technological platform with an extremely wide scope of controllable properties.
Hydrogel is made up almost entirely of water, yet can thicken to produce a substance 100-1000 times stronger than any other gel of its kind.
This is because it is composed of two very long elastic-like molecules that form strong covalent bonds with each other to form a 3D network, like a cage, that holds the water. By adjusting the number of bonds, the physico-chemical properties of the gel can be manipulated to make it thick, thin or sticky. The gel also has the capability to hold molecules of other substances, whether water soluble or water insoluble (e.g. oil).
For more information about AGT visit agtsciences
Source:
Emma Banks
University of Bradford
Racial Disparity Observed In Varus And Valgus Thrust Study Of Knee OA
A recent study determined that African-Americans were less likely to have a varus thrust, but more likely to have valgus thrust than Caucasians. Varus thrust is visualized during gait as the worsening or abrupt onset of varus (bow-legged) alignment as the leg accepts weight, with a return to less varus and more neutral alignment during lift-off of the foot and the swing phase of gait. Prior research has shown that varus thrust seen in gait is associated with a 4-fold increase in the risk of progression of knee osteoarthritis (OA). Disparity in thrust presence between the races may help explain differences in the pattern of osteoarthritic involvement at the knee. Study findings are published in the May issue of Arthritis & Rheumatism, a journal of the American College of Rheumatology.
OA is the most common type of arthritis, characterized by cartilage damage and loss, and causing pain, inflammation, and loss of joint motion. According to The National Institute of Arthritis and Musculoskeletal and Skin Diseases, roughly 27 million Americans 25 years and older have OA. With the aging population, experts project that by 2030 20% of Americans (72 million) will be at risk for developing this disabling disease.
In the current study, a team of researchers from the Feinberg School of Medicine at Northwestern University assessed frequency of varus and valgus thrust in African-Americans and Caucasians and identified factors associated with thrust presence in members of the Osteoarthritis Initiative (OAI) cohort. The OAI thrust study included 3,592 persons (594 African-Americans and 2,998 Caucasians) who were split into two groups: participants without knee OA (n=1,566) and those with OA in one or both knees (n=2026). Those participants without knee OA had a mean age 61 years, a mean body mass index (BMI) of 27.6 kg/m2, and 58.7% were women. In persons with knee OA, the mean age was 63.4 years, the mean BMI was 28.4 kg/m2, and 57.5% were women.
The study revealed that 32.1% of subjects without OA and 36.7% of those with OA had a varus thrust. Valgus thrust was less frequent: 7.2% without OA and 9.1% with OA. The odds of varus thrust were significantly less for African-Americans compared to Caucasians in both disease subgroups, after controlling for other factors. Other factors associated with varus thrust presence in persons without knee OA were age, BMI, varus malalignment, gender (reduced odds in women), and knee extensor strength (reduced odds with greater strength), and, in persons with knee OA, more severe OA disease, varus malalignment, and gender (reduced odds in women).
The odds of valgus thrust were significantly greater for African-Americans compared with Caucasians, in persons without and with knee OA. Also associated with valgus thrust presence in persons without knee OA were valgus malalignment and, in persons with knee OA, more severe lateral disease and valgus malalignment.
"To our knowledge, this is the first report on the frequency of varus and valgus thrust in African-Americans and Caucasians either in persons with or at higher risk of developing knee OA," Dr. Sharma commented. "Further investigation of methods to quantify the elements of a thrust, such as its force and loading rate, will enhance understanding of the mechanism of a thrust effect," concluded the authors. The researchers also caution that persons without knee OA in the OAI thrust study were at high risk of developing it, and thus frequency estimates should not be applied to the general population.
Article: "Frequency of Varus and Valgus Thrust and Factors Associated With Thrust Presence in Persons With or at Higher Risk of Developing Knee Osteoarthritis." Alison Chang, Marc Hochberg, Jing Song, Dorothy Dunlop, Joan S. Chmiel, Michael Nevitt, Karen Hayes, Charles Eaton, Joan Bathon, Rebecca Jackson, C. Kent Kwoh, and Leena Sharma. Arthritis & Rheumatism; Published Online: April 29, 2010 (DOI: 10.1002/art.27377); Print Issue Date: May 2010.
Source:
Dawn Peters
Wiley-Blackwell
OA is the most common type of arthritis, characterized by cartilage damage and loss, and causing pain, inflammation, and loss of joint motion. According to The National Institute of Arthritis and Musculoskeletal and Skin Diseases, roughly 27 million Americans 25 years and older have OA. With the aging population, experts project that by 2030 20% of Americans (72 million) will be at risk for developing this disabling disease.
In the current study, a team of researchers from the Feinberg School of Medicine at Northwestern University assessed frequency of varus and valgus thrust in African-Americans and Caucasians and identified factors associated with thrust presence in members of the Osteoarthritis Initiative (OAI) cohort. The OAI thrust study included 3,592 persons (594 African-Americans and 2,998 Caucasians) who were split into two groups: participants without knee OA (n=1,566) and those with OA in one or both knees (n=2026). Those participants without knee OA had a mean age 61 years, a mean body mass index (BMI) of 27.6 kg/m2, and 58.7% were women. In persons with knee OA, the mean age was 63.4 years, the mean BMI was 28.4 kg/m2, and 57.5% were women.
The study revealed that 32.1% of subjects without OA and 36.7% of those with OA had a varus thrust. Valgus thrust was less frequent: 7.2% without OA and 9.1% with OA. The odds of varus thrust were significantly less for African-Americans compared to Caucasians in both disease subgroups, after controlling for other factors. Other factors associated with varus thrust presence in persons without knee OA were age, BMI, varus malalignment, gender (reduced odds in women), and knee extensor strength (reduced odds with greater strength), and, in persons with knee OA, more severe OA disease, varus malalignment, and gender (reduced odds in women).
The odds of valgus thrust were significantly greater for African-Americans compared with Caucasians, in persons without and with knee OA. Also associated with valgus thrust presence in persons without knee OA were valgus malalignment and, in persons with knee OA, more severe lateral disease and valgus malalignment.
"To our knowledge, this is the first report on the frequency of varus and valgus thrust in African-Americans and Caucasians either in persons with or at higher risk of developing knee OA," Dr. Sharma commented. "Further investigation of methods to quantify the elements of a thrust, such as its force and loading rate, will enhance understanding of the mechanism of a thrust effect," concluded the authors. The researchers also caution that persons without knee OA in the OAI thrust study were at high risk of developing it, and thus frequency estimates should not be applied to the general population.
Article: "Frequency of Varus and Valgus Thrust and Factors Associated With Thrust Presence in Persons With or at Higher Risk of Developing Knee Osteoarthritis." Alison Chang, Marc Hochberg, Jing Song, Dorothy Dunlop, Joan S. Chmiel, Michael Nevitt, Karen Hayes, Charles Eaton, Joan Bathon, Rebecca Jackson, C. Kent Kwoh, and Leena Sharma. Arthritis & Rheumatism; Published Online: April 29, 2010 (DOI: 10.1002/art.27377); Print Issue Date: May 2010.
Source:
Dawn Peters
Wiley-Blackwell
Diseased Cartilage Harbors Unique Migratory Progenitor Cells
A new study finds previously unidentified fibrocartilage-forming progenitor cells in degenerating, diseased human cartilage, but not in cartilage from healthy joints. The research, published by Cell Press in the April 3rd issue of the journal Cell Stem Cell, provides valuable insights into the reparative potential of cartilage and may lead to development of regenerative therapies for arthritis.
Osteoarthritis (OA) is an incurable degenerative disease caused by a progressive deterioration of the cartilage that cushions and protects joints. "OA is the most common musculoskeletal disease in the elderly and is likely to be the fourth-leading cause of disability by the year 2020," explains senior study author Dr. Nicolai Miosge from Georg August University in Goettingen, Germany. "This is our motivation for the further exploration of OA treatment options, including regenerative cell biological therapy."
Previous research has suggested that OA tissue may harbor cells which possess an ability to contribute to the repair of damaged cartilage. It has even been suggested that these potentially regenerative cells may be specifically recruited to degenerating cartilage. In their study, Dr. Miosge and colleagues sought to determine whether diseased adult cartilage tissue contains progenitor-like cells that exhibit migratory capabilities.
The researchers discovered that cartilage from humans with late-stage OA contains a unique population of progenitor cells called chondrogenic progenitor cells (CPC). The CPCs, which were not present in healthy cartilage, exhibited many characteristics associated with tissue-specific stem cells, including migratory activity and the potential to generate new cartilage. Although the origin of the CPCs was not clear, there was some evidence that they migrated from the bone marrow.
Taken together, the findings establish CPCs as an exciting future target for stimulating the repair and regeneration of damaged cartilage. "Our results offer new insights into the biology of progenitor cells in the context of diseased cartilage tissue," offers Dr. Miosge. "We hope ultimately to work towards utilizing these cells - which are already present in diseased tissue - for the development of regenerative OA therapies." Additional research is needed to identify the optimal conditions for promoting and sustaining the cartilage-producing potential of CPCs.
Notes:
The reseachers include Sebastian Koelling, Georg August University, Goettingen, Germany; Jenny Kruegel, Georg August University, Goettingen, Germany; Malte Irmer, Georg August University, Goettingen, Germany; Jan Ragnar Path, Georg August University, Goettingen, Germany; Boguslawa Sadowski, Georg August University, Goettingen, Germany; Xavier Miro, Max-Planck-Institute for Biophysical Chemistry, Goettingen, Germany; and Nicolai Miosge, Georg August University, Goettingen, Germany.
Contact: Cathleen Genova
Cell Press
Osteoarthritis (OA) is an incurable degenerative disease caused by a progressive deterioration of the cartilage that cushions and protects joints. "OA is the most common musculoskeletal disease in the elderly and is likely to be the fourth-leading cause of disability by the year 2020," explains senior study author Dr. Nicolai Miosge from Georg August University in Goettingen, Germany. "This is our motivation for the further exploration of OA treatment options, including regenerative cell biological therapy."
Previous research has suggested that OA tissue may harbor cells which possess an ability to contribute to the repair of damaged cartilage. It has even been suggested that these potentially regenerative cells may be specifically recruited to degenerating cartilage. In their study, Dr. Miosge and colleagues sought to determine whether diseased adult cartilage tissue contains progenitor-like cells that exhibit migratory capabilities.
The researchers discovered that cartilage from humans with late-stage OA contains a unique population of progenitor cells called chondrogenic progenitor cells (CPC). The CPCs, which were not present in healthy cartilage, exhibited many characteristics associated with tissue-specific stem cells, including migratory activity and the potential to generate new cartilage. Although the origin of the CPCs was not clear, there was some evidence that they migrated from the bone marrow.
Taken together, the findings establish CPCs as an exciting future target for stimulating the repair and regeneration of damaged cartilage. "Our results offer new insights into the biology of progenitor cells in the context of diseased cartilage tissue," offers Dr. Miosge. "We hope ultimately to work towards utilizing these cells - which are already present in diseased tissue - for the development of regenerative OA therapies." Additional research is needed to identify the optimal conditions for promoting and sustaining the cartilage-producing potential of CPCs.
Notes:
The reseachers include Sebastian Koelling, Georg August University, Goettingen, Germany; Jenny Kruegel, Georg August University, Goettingen, Germany; Malte Irmer, Georg August University, Goettingen, Germany; Jan Ragnar Path, Georg August University, Goettingen, Germany; Boguslawa Sadowski, Georg August University, Goettingen, Germany; Xavier Miro, Max-Planck-Institute for Biophysical Chemistry, Goettingen, Germany; and Nicolai Miosge, Georg August University, Goettingen, Germany.
Contact: Cathleen Genova
Cell Press
New Way Of Classifying Rheumatoid Arthritis Aimed At Identifying The Disease Earlier
The American College of Rheumatology announced the release of revised classification criteria (created in collaboration with the European League Against Rheumatism) for rheumatoid arthritis, which will allow the study of treatments for RA at much earlier stages of the disease before joint damage occurs ultimately leading to better patient outcomes.
Rheumatoid arthritis is a chronic disease that causes pain, stiffness, swelling, and limitation in the motion and function of multiple joints. Though joints are the principal body parts affected by RA, inflammation can develop in the organs as well. An estimated 1.3 million Americans have RA, and the disease typically affects women twice as often as men.
Classification criteria are the standard and accepted means by which researchers define a disease. They allow researchers to define individuals as having or not having a given disease, helping to standardize recruitment into clinical trials and other research studies. Although not intended as criteria for diagnosis in clinical practice, with some additional research, classification criteria may be modified and adopted for such use.
Classification criteria are typically updated as knowledge changes, which is the case with the new RA criteria published in the College's journal, Arthritis & Rheumatism. The previous criteria were created in 1987. Since that time, new therapies have emerged that can prevent joint damage in people with RA. With these modern therapies, the goal of treatment is to prevent people from reaching the point where their RA is causing chronic damage to their joints.
"The 1987 criteria actually posed a major barrier to the study of treatments designed to prevent joint damage in RA," explains Gillian Hawker, MD; senior author of the new criteria. "Many patients did not fulfill the previous RA classification criteria until their disease was well-advanced, and in many cases joint damage had already occurred. This truly limited RA researchers from studying the disease at its earlier phases, which is critical to the development of new treatments to prevent damage."
In 2008, the ACR began a collaborative project with the EULAR to create the first new set of RA classification criteria in over 20 years. To establish the new criteria, researchers completed three phases of work. The first phase (led by EULAR) involved reviewing existing data collected from patients with early arthritis to determine which factors best identified patients who were, according to Daniel Aletaha, MD, MS; lead author of this phase of research, "at a high risk of developing the more persistent and erosive arthritis that we currently consider to be RA." Dr. Aletaha also explains that this phase of research is an important component to the overall project as "all classification criteria need to be built on scientific evidence, either from the literature or as with these criteria from extensive analysis of real patient data."
The second phase of work (led by the ACR) was aimed at reaching consensus among practicing rheumatologists on which factors were most important in determining a person's likelihood of developing the chronic joint damage that has been known for many years as the hallmark of RA. "Both scientific evidence and the experience of RA experts needed to be considered in the development of the new criteria to ensure all important factors were identified," explains criteria author Tuhina Neogi, MD, PhD. "Additionally, ensuring the new criteria reflects the opinions of front-line rheumatologists diagnosing and treating patients in clinical practice is key to their ultimate acceptance."
In phase three, researchers integrated the findings from the first two phases of work, refined a scoring system, and determined the optimal cut off point to define the disease. Patients to whom these criteria should be applied must have confirmed presence of joint swelling, indicating synovitis the inflammation of the synovial membrane, which lines a joint in at least one joint, and no other possible diagnosis that might better explain the symptoms (such as lupus or gout).
"To be classified as having 'definite RA,' patients must receive a score of six or greater (out of a possible 10)," explains Alan Silman, MD who initiated the project. "The scoring system takes into consideration the number and site/size of involved joints, laboratory tests of inflammation and auto-immunity, and symptom duration."
Researchers continue to make great strides in RA research. The creation of this new set of classification criteria is expected to further accelerate the research being done in this field. The next logical step, according to Dr. Hawker, is to use these classification criteria as the basis for the development of diagnostic criteria for RA, for use by practicing rheumatologists.
"Under the correct circumstances, new knowledge resulting from rheumatology research can quickly move into applicable treatments for patients," explains ACR President Stanley B. Cohen, MD. "We believe these new classification criteria will open the door to more meaningful studies of RA and will eventually lead to changes in the diagnosis and treatment of the disease. This is an important step for RA researchers, practicing rheumatologists and patients."
Source: American College of Rheumatology (ACR)
Rheumatoid arthritis is a chronic disease that causes pain, stiffness, swelling, and limitation in the motion and function of multiple joints. Though joints are the principal body parts affected by RA, inflammation can develop in the organs as well. An estimated 1.3 million Americans have RA, and the disease typically affects women twice as often as men.
Classification criteria are the standard and accepted means by which researchers define a disease. They allow researchers to define individuals as having or not having a given disease, helping to standardize recruitment into clinical trials and other research studies. Although not intended as criteria for diagnosis in clinical practice, with some additional research, classification criteria may be modified and adopted for such use.
Classification criteria are typically updated as knowledge changes, which is the case with the new RA criteria published in the College's journal, Arthritis & Rheumatism. The previous criteria were created in 1987. Since that time, new therapies have emerged that can prevent joint damage in people with RA. With these modern therapies, the goal of treatment is to prevent people from reaching the point where their RA is causing chronic damage to their joints.
"The 1987 criteria actually posed a major barrier to the study of treatments designed to prevent joint damage in RA," explains Gillian Hawker, MD; senior author of the new criteria. "Many patients did not fulfill the previous RA classification criteria until their disease was well-advanced, and in many cases joint damage had already occurred. This truly limited RA researchers from studying the disease at its earlier phases, which is critical to the development of new treatments to prevent damage."
In 2008, the ACR began a collaborative project with the EULAR to create the first new set of RA classification criteria in over 20 years. To establish the new criteria, researchers completed three phases of work. The first phase (led by EULAR) involved reviewing existing data collected from patients with early arthritis to determine which factors best identified patients who were, according to Daniel Aletaha, MD, MS; lead author of this phase of research, "at a high risk of developing the more persistent and erosive arthritis that we currently consider to be RA." Dr. Aletaha also explains that this phase of research is an important component to the overall project as "all classification criteria need to be built on scientific evidence, either from the literature or as with these criteria from extensive analysis of real patient data."
The second phase of work (led by the ACR) was aimed at reaching consensus among practicing rheumatologists on which factors were most important in determining a person's likelihood of developing the chronic joint damage that has been known for many years as the hallmark of RA. "Both scientific evidence and the experience of RA experts needed to be considered in the development of the new criteria to ensure all important factors were identified," explains criteria author Tuhina Neogi, MD, PhD. "Additionally, ensuring the new criteria reflects the opinions of front-line rheumatologists diagnosing and treating patients in clinical practice is key to their ultimate acceptance."
In phase three, researchers integrated the findings from the first two phases of work, refined a scoring system, and determined the optimal cut off point to define the disease. Patients to whom these criteria should be applied must have confirmed presence of joint swelling, indicating synovitis the inflammation of the synovial membrane, which lines a joint in at least one joint, and no other possible diagnosis that might better explain the symptoms (such as lupus or gout).
"To be classified as having 'definite RA,' patients must receive a score of six or greater (out of a possible 10)," explains Alan Silman, MD who initiated the project. "The scoring system takes into consideration the number and site/size of involved joints, laboratory tests of inflammation and auto-immunity, and symptom duration."
Researchers continue to make great strides in RA research. The creation of this new set of classification criteria is expected to further accelerate the research being done in this field. The next logical step, according to Dr. Hawker, is to use these classification criteria as the basis for the development of diagnostic criteria for RA, for use by practicing rheumatologists.
"Under the correct circumstances, new knowledge resulting from rheumatology research can quickly move into applicable treatments for patients," explains ACR President Stanley B. Cohen, MD. "We believe these new classification criteria will open the door to more meaningful studies of RA and will eventually lead to changes in the diagnosis and treatment of the disease. This is an important step for RA researchers, practicing rheumatologists and patients."
Source: American College of Rheumatology (ACR)
Hope For Arthritis Stems From Within
Leeds bioengineers have developed an innovative technique for cartilage repair combining the self-healing powers of the body with stem cell science to help young people avoid debilitating knee problems and give hope to arthritis sufferers.
Current treatments of cartilage defects in the knee are expensive, have lengthy recovery times, and can even cause as much damage as good. "We're responding to a real need," said reader in bioengineering Dr Bahaa Seedhom.
"Orthopaedic surgeons are looking for ways to repair cartilage defects in young people which will delay, maybe even prevent, the need for total knee replacement."
The bioengineers have invented a repair technique - and tools - that cut surgery times from two hours to ten minutes, and can have patients back on their feet within three weeks. The treatment involves a surgical technique called subchondral drilling, where holes are drilled into the bone beneath the cartilage in the damaged site, causing bleeding from the bone marrow, which stimulates stem cells to grow tissue within the damaged area. Surgeons then implant a felt-like pad, to encourage the cells to expand and grow into tissue.
As the treatment uses the body's own stem cells, it is much cheaper than existing methods, where tissue is engineered outside the body and then implanted. The system has potential for widescale applications. "Initially young people with small defects will be most suitable for treatment, but once the system has been put through its paces it might well be used for larger defects in older arthritic patients," said Dr Seedhom.
Dr Seedhom is joined on the project by Drs Toyoda, Luo, Lorrison and Michael Pullan from bioengineering. The arthritis research campaign has awarded the project ?131,000 to explain the cartilage regeneration process, and Smith and Nephew have begun an evaluation programme to commercialise the technology for clinical use within four years.
For more information on the academic unit of musculoskeletal disease see leeds.ac.uk/medicine/musculoskeletal/bioengeneering.html
Current treatments of cartilage defects in the knee are expensive, have lengthy recovery times, and can even cause as much damage as good. "We're responding to a real need," said reader in bioengineering Dr Bahaa Seedhom.
"Orthopaedic surgeons are looking for ways to repair cartilage defects in young people which will delay, maybe even prevent, the need for total knee replacement."
The bioengineers have invented a repair technique - and tools - that cut surgery times from two hours to ten minutes, and can have patients back on their feet within three weeks. The treatment involves a surgical technique called subchondral drilling, where holes are drilled into the bone beneath the cartilage in the damaged site, causing bleeding from the bone marrow, which stimulates stem cells to grow tissue within the damaged area. Surgeons then implant a felt-like pad, to encourage the cells to expand and grow into tissue.
As the treatment uses the body's own stem cells, it is much cheaper than existing methods, where tissue is engineered outside the body and then implanted. The system has potential for widescale applications. "Initially young people with small defects will be most suitable for treatment, but once the system has been put through its paces it might well be used for larger defects in older arthritic patients," said Dr Seedhom.
Dr Seedhom is joined on the project by Drs Toyoda, Luo, Lorrison and Michael Pullan from bioengineering. The arthritis research campaign has awarded the project ?131,000 to explain the cartilage regeneration process, and Smith and Nephew have begun an evaluation programme to commercialise the technology for clinical use within four years.
For more information on the academic unit of musculoskeletal disease see leeds.ac.uk/medicine/musculoskeletal/bioengeneering.html
Unigene Reports Continuation Of Phase III Study Of Oral Calcitonin In Osteoarthritis Patients
Unigene Laboratories, Inc. (OTCBB: UGNE) announced that Novartis and its license partner Nordic Bioscience [the "Sponsor"] have decided to continue the companies' two-year, Phase III Study 2302 assessing safety and efficacy of oral calcitonin in patients with osteoarthritis of the knee. Novartis has a worldwide license to produce recombinant calcitonin under Unigene's patented SecraPep® E. coli manufacturing technology.
An independent Data Monitoring Committee (DMC) reviewed and conducted a "futility" analysis of one-year data for all patients enrolled in Study 2302, including both an assessment of safety and efficacy parameters. The DMC concluded there is no reason to stop the study because of safety findings. In addition, the DMC concluded there is no reason to continue the study because of efficacy findings; however, the DMC also determined the final decision whether to continue Study 2302 rests with the study Sponsor. Accordingly, the relevant Health Authorities and Ethics Committees will be informed by the Sponsor about the DMC recommendation and about the decision to continue the study.
Conclusions after these kinds of interim analysis are usually based on whether or not the DMC has seen either major safety concerns, or a significant imbalance in adverse events, or an unsatisfactory efficacy outcome.
Based on a similar one-year futility analysis, the DMC recommended in December 2009 that Novartis and Nordic Bioscience continue a parallel two-year, Phase III Study 2301 in patients with osteoarthritis of the knee. At that time, the DMC also recommended continuation of a two-year, Phase III Study 2303 of oral calcitonin in patients with osteoporosis.
It is currently intended by the Sponsor that the entire clinical program of oral calcitonin in osteoarthritis and osteoporosis will continue, and Novartis and Nordic Bioscience will closely work together to assess next steps once the final data of Study 2301 are available, currently expected to be in 4Q 2010.
Unigene President and CEO Ashleigh Palmer commented, "We believe our manufacturing license agreement with Novartis provides strong validation of Unigene's leading position in peptide manufacturing. We look forward to hearing of next steps in the program."
Source:
Unigene Laboratories, Inc.
An independent Data Monitoring Committee (DMC) reviewed and conducted a "futility" analysis of one-year data for all patients enrolled in Study 2302, including both an assessment of safety and efficacy parameters. The DMC concluded there is no reason to stop the study because of safety findings. In addition, the DMC concluded there is no reason to continue the study because of efficacy findings; however, the DMC also determined the final decision whether to continue Study 2302 rests with the study Sponsor. Accordingly, the relevant Health Authorities and Ethics Committees will be informed by the Sponsor about the DMC recommendation and about the decision to continue the study.
Conclusions after these kinds of interim analysis are usually based on whether or not the DMC has seen either major safety concerns, or a significant imbalance in adverse events, or an unsatisfactory efficacy outcome.
Based on a similar one-year futility analysis, the DMC recommended in December 2009 that Novartis and Nordic Bioscience continue a parallel two-year, Phase III Study 2301 in patients with osteoarthritis of the knee. At that time, the DMC also recommended continuation of a two-year, Phase III Study 2303 of oral calcitonin in patients with osteoporosis.
It is currently intended by the Sponsor that the entire clinical program of oral calcitonin in osteoarthritis and osteoporosis will continue, and Novartis and Nordic Bioscience will closely work together to assess next steps once the final data of Study 2301 are available, currently expected to be in 4Q 2010.
Unigene President and CEO Ashleigh Palmer commented, "We believe our manufacturing license agreement with Novartis provides strong validation of Unigene's leading position in peptide manufacturing. We look forward to hearing of next steps in the program."
Source:
Unigene Laboratories, Inc.
Arthritis Drug Might Reduce Fatigue In Cancer Patients
Researchers here have found evidence that combining a drug typically used to treat rheumatoid arthritis with chemotherapy might help reduce fatigue and muscle wasting that often afflicts cancer patients.
The findings of the preliminary study with 24 patients are reported in the April issue of the Journal of Clinical Oncology.
"Even though this was a small study, we found that we could deliver more chemotherapy when combined with the drug etanercept," said lead author Miguel A. Villalona-Calero, an associate professor of hematology and oncology and of pharmacology at Ohio State.
"This shows promise in helping reduce fatigue in cancer patients while increasing their ability to tolerate higher doses of chemotherapy on a more frequent basis," said Villalona-Calero, who is also researcher at The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC - James).
Patients' fatigue - the state of overwhelming and sustained exhaustion that is not relieved by rest - often hinders physicians' ability to deliver chemotherapy to them on schedule because of their weakened state.
The fatigue and muscle wasting that are associated with cancer are largely caused when immune cells release a substance known as tumor necrosis factor (TNF). Although TNF historically has been studied for its anticancer properties, recent studies indicate that TNF probably promotes tumor growth instead of hindering it.
The drug etanercept is a decoy receptor that blocks interaction with TNF. The researchers hypothesized that the drug might therefore work like a sponge to "soak up" TNF and lower the amount of the substance in the body, which would decrease tumor growth and help reduce fatigue.
They tested the idea in patients who were being treated with the chemotherapy drug docetaxel.
Initially, 12 patients with a variety of advanced solid malignancies that were resistant to conventional treatment, or for which no effective treatment existed, were randomly assigned to two groups, one receiving docetaxel, and one receiving docetaxel along with etanercept. Subsequently, an additional 12 patients who were later added to the study received higher doses of docetaxel combined with etanercept.
Patients were evaluated and answered weekly questionnaires about their perceived fatigue and weakness. Although only a limited group of patients received docetaxel without etanercept, the questionnaires showed that they have increased fatigue compared to the patients who received etanercept.
Researchers concluded that the addition of etanercept is safe and had no impact on the concentration of the chemotherapy drugs in the body. The finding that patients could tolerate higher doses of the chemotherapy drug suggests that the use of drugs to block TNF might improve the effectiveness of cancer therapies, Villalona-Calero said.
Others involved in the study were J. Paul Monk, Michael A. Caligiuri, Larry J. Schaaf, Gregory W. Otterson, Denis Guttridge, Chris Rhoades, Manisha Shah, Gary Phillips and Tamara Criswell, all of the Ohio State cancer program.
The study is funded by Amgen, Inc. and by the OSUCCC - James.
Contact: Eileen Scahill
Ohio State University
The findings of the preliminary study with 24 patients are reported in the April issue of the Journal of Clinical Oncology.
"Even though this was a small study, we found that we could deliver more chemotherapy when combined with the drug etanercept," said lead author Miguel A. Villalona-Calero, an associate professor of hematology and oncology and of pharmacology at Ohio State.
"This shows promise in helping reduce fatigue in cancer patients while increasing their ability to tolerate higher doses of chemotherapy on a more frequent basis," said Villalona-Calero, who is also researcher at The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC - James).
Patients' fatigue - the state of overwhelming and sustained exhaustion that is not relieved by rest - often hinders physicians' ability to deliver chemotherapy to them on schedule because of their weakened state.
The fatigue and muscle wasting that are associated with cancer are largely caused when immune cells release a substance known as tumor necrosis factor (TNF). Although TNF historically has been studied for its anticancer properties, recent studies indicate that TNF probably promotes tumor growth instead of hindering it.
The drug etanercept is a decoy receptor that blocks interaction with TNF. The researchers hypothesized that the drug might therefore work like a sponge to "soak up" TNF and lower the amount of the substance in the body, which would decrease tumor growth and help reduce fatigue.
They tested the idea in patients who were being treated with the chemotherapy drug docetaxel.
Initially, 12 patients with a variety of advanced solid malignancies that were resistant to conventional treatment, or for which no effective treatment existed, were randomly assigned to two groups, one receiving docetaxel, and one receiving docetaxel along with etanercept. Subsequently, an additional 12 patients who were later added to the study received higher doses of docetaxel combined with etanercept.
Patients were evaluated and answered weekly questionnaires about their perceived fatigue and weakness. Although only a limited group of patients received docetaxel without etanercept, the questionnaires showed that they have increased fatigue compared to the patients who received etanercept.
Researchers concluded that the addition of etanercept is safe and had no impact on the concentration of the chemotherapy drugs in the body. The finding that patients could tolerate higher doses of the chemotherapy drug suggests that the use of drugs to block TNF might improve the effectiveness of cancer therapies, Villalona-Calero said.
Others involved in the study were J. Paul Monk, Michael A. Caligiuri, Larry J. Schaaf, Gregory W. Otterson, Denis Guttridge, Chris Rhoades, Manisha Shah, Gary Phillips and Tamara Criswell, all of the Ohio State cancer program.
The study is funded by Amgen, Inc. and by the OSUCCC - James.
Contact: Eileen Scahill
Ohio State University
Combination Of Methotrexate And Prednisone Produces Remission In People With Newly-Developed Rheumatoid Arthritis And Undifferentiated Arthritis
People with newly-developed rheumatoid arthritis or undifferentiated arthritis may be able to achieve remission, with continued drug therapy, after four months of treatment with methotrexate and prednisone, according to research presented this week at the American College of Rheumatology Annual Scientific Meeting in Atlanta.
Rheumatoid arthritis is a chronic disease that causes pain, stiffness, swelling, and limitation in the motion and function of multiple joints. Though joints are the principal body parts affected by RA, inflammation can develop in other organs as well. An estimated 1.3 million Americans have RA, and the disease typically affects women twice as often as men. The new ACR/EULAR 2010 Rheumatoid Arthritis Classification Criteria are based on the recognition that undifferentiated arthritis may be the earliest clinical manifestation of RA.
Researchers recently assessed whether people with RA (which had developed less than two years before the start of the study) or undifferentiated arthritis (defined, for this study, as having arthritis in more than one joint and being considered at risk for developing RA) could achieve remission after four months of taking a combination of methotrexate and prednisone.
Throughout the course of the study, researchers followed 261 people with RA and 161 people with undifferentiated arthritis who were taking 25 mg per week of methotrexate and 60 mg per day of prednisone, which was tapered down to 7.5 mg per day over the course of seven weeks.
According to C. F. (Ren?©e) Allaart, MD, PhD associate professor of rheumatology at Leiden University Medical Center in Leiden, The Netherlands, and an investigator in the study this is first study to treat early RA and undifferentiated arthritis patients with progressive combination therapy, which was previously reserved for active, more advanced RA. The goal was to see if participants could achieve remission based on a Disease Activity Score under 1.6. Researchers measured this clinical outcome and considered functional abilities when making their final assessments of the success of the combination of methotrexate and prednisone.
They found that remission was achieved in 153 (58.6 percent) of the participants with RA and 107 (66.5 percent) of the participants with undifferentiated arthritis. Althogether, the disease went into remission in 63 percent of patients. There was improvement in the average DAS scores of participants of 1.90 for participants with RA, and 1.32 in participants with undifferentiated arthritis. There was also an improvement in overall functionality reported by participants in both groups. Participants in both groups who began the study with lower DAS scores were more likely to achieve remission after four months of the combined treatment.
"The results show that in this group of patients with earlier, and on average less active RA remission percentages are higher than with similar treatment in more active RA, and that the addition of high-tapered-to-low prednisone to methotrexate works in undifferentiated arthritis," says Dr. Allaart, noting that previously published early remission rates for active RA are less than 30 percent (depending on initial treatment). "We now will try to taper and stop the medication in order to achieve drug-free remission."
This ongoing study will continue to report on the patients who achieved remission and had their medications discontinued. More than 600 patients have now been included, and the study will begin a second phase where participants with RA and undifferentiated arthritis who have not achieved remission while taking methotrexate with prednisone are randomly placed in two treatment groups. One group will be given multiple disease-modifying antirheumatic drugs (such as methotrexate, sulfasalazine, hydroxychloroquine, and low-dose prednisone), while the other group will be given an anti-TNF (adalimumab) with methotrexate. The aim remains to achieve (ultimately drug-free) remission.
"The results of the randomized, second phase of the study will determine whether there is still a place for conventional DMARD therapy after failure on methotrexate and prednisone, or whether anti-TNF is the best option for early remission induction treatment," Dr. Allaart says.
For now, she suggests the optimal strategy is to start treatment early and aim at remission. "A short initial course of prednisone, even at a relatively high dose, is probably preferred over delayed but long-term low prednisone dosages in patients with RA," she says. "We found that even with relatively mild or little joint involvement, patients are motivated to take progressive medication in order to achieve early remission."
Patients should talk to their rheumatologists to determine their best course of treatment.
The American College of Rheumatology is an international professional medical society that represents more than 8,000 rheumatologists and rheumatology health professionals around the world. Its mission is to advance rheumatology. The ACR/ARHP Annual Scientific Meeting is the premier meeting in rheumatology.
Editor's Notes: K V C de Boer will present this research during the ACR Annual Scientific Meeting at the Georgia World Congress Center at 3:30 PM on Tuesday, November 9 in the Sidney J. Marcus Auditorium. Dr. Allaart will be available for media questions and briefing at 8:30 AM on Monday, November 8 in the on-site press conference room, B 212.
Learn more about living well with rheumatic disease as well as rheumatologists and the role they play in health care. Also, discover how the ACR Research and Education Foundation's Within Our Reach: Finding a Cure for Rheumatoid Arthritis campaign is accelerating RA research.
Presentation Number: 1396
Induction Therapy with Methotrexate and Prednisone in Rheumatoid or Very Early Arthritic Disease: IMPROVED Study.
K V C de Boer (LUMC, Leiden, Leiden)
K Visser (LUMC, Leiden, Leiden)
H K Ronday (Haga Hospital, the Hague)
A A Schouffoer (Groene Hart Hospital, Gouda)
J H L M Groenendael (Franciscus Hospital, Roosendaal)
A J Peeters (Reinier de Graaf Gasthuis, Delft)
I Speyer (Bronovo Hospital, the Hague)
G Coll?©e (MCH, the Hague)
P B J Sonnaville (Oosterschelde Hospital, Goes)
B A M Grillet (Zorgsaam, Terneuzen)
T. W J Huizinga (LUMC, Leiden, Leiden)
C F Allaart, MD, PhD (LUMC, Leiden, Leiden)
Aim: To assess the rate of remission after 4 months of treatment with methotrexate (MTX) and a tapered high dose prednisone in patients with recent onset rheumatoid or undifferentiated arthritis (RA and UA), in relation to clinical and demographic baseline criteria.
Methods: IMPROVED is a multicenter single blind clinical study in patients with recent onset RA and UA, with an open label induction phase with MTX 25 mg/wk and prednisone 60 mg/day tapered to 7.5 mg/day in 7 weeks, aimed at achieving DAS < 1.6, which will be followed by tapering to drug free if remission persists, or randomization to multi-DMARD or MTX + adalimumab if DAS ?‰? 1.6 after 4 months. To date, 161 patients with UA (arthritis > 1 joint, at risk for developing RA by estimation of a rheumatologist) and 261 patients with recent onset RA (ACR 1987 criteria, symptom duration < two years) were included. Clinical outcomes (% remission DAS
Rheumatoid arthritis is a chronic disease that causes pain, stiffness, swelling, and limitation in the motion and function of multiple joints. Though joints are the principal body parts affected by RA, inflammation can develop in other organs as well. An estimated 1.3 million Americans have RA, and the disease typically affects women twice as often as men. The new ACR/EULAR 2010 Rheumatoid Arthritis Classification Criteria are based on the recognition that undifferentiated arthritis may be the earliest clinical manifestation of RA.
Researchers recently assessed whether people with RA (which had developed less than two years before the start of the study) or undifferentiated arthritis (defined, for this study, as having arthritis in more than one joint and being considered at risk for developing RA) could achieve remission after four months of taking a combination of methotrexate and prednisone.
Throughout the course of the study, researchers followed 261 people with RA and 161 people with undifferentiated arthritis who were taking 25 mg per week of methotrexate and 60 mg per day of prednisone, which was tapered down to 7.5 mg per day over the course of seven weeks.
According to C. F. (Ren?©e) Allaart, MD, PhD associate professor of rheumatology at Leiden University Medical Center in Leiden, The Netherlands, and an investigator in the study this is first study to treat early RA and undifferentiated arthritis patients with progressive combination therapy, which was previously reserved for active, more advanced RA. The goal was to see if participants could achieve remission based on a Disease Activity Score under 1.6. Researchers measured this clinical outcome and considered functional abilities when making their final assessments of the success of the combination of methotrexate and prednisone.
They found that remission was achieved in 153 (58.6 percent) of the participants with RA and 107 (66.5 percent) of the participants with undifferentiated arthritis. Althogether, the disease went into remission in 63 percent of patients. There was improvement in the average DAS scores of participants of 1.90 for participants with RA, and 1.32 in participants with undifferentiated arthritis. There was also an improvement in overall functionality reported by participants in both groups. Participants in both groups who began the study with lower DAS scores were more likely to achieve remission after four months of the combined treatment.
"The results show that in this group of patients with earlier, and on average less active RA remission percentages are higher than with similar treatment in more active RA, and that the addition of high-tapered-to-low prednisone to methotrexate works in undifferentiated arthritis," says Dr. Allaart, noting that previously published early remission rates for active RA are less than 30 percent (depending on initial treatment). "We now will try to taper and stop the medication in order to achieve drug-free remission."
This ongoing study will continue to report on the patients who achieved remission and had their medications discontinued. More than 600 patients have now been included, and the study will begin a second phase where participants with RA and undifferentiated arthritis who have not achieved remission while taking methotrexate with prednisone are randomly placed in two treatment groups. One group will be given multiple disease-modifying antirheumatic drugs (such as methotrexate, sulfasalazine, hydroxychloroquine, and low-dose prednisone), while the other group will be given an anti-TNF (adalimumab) with methotrexate. The aim remains to achieve (ultimately drug-free) remission.
"The results of the randomized, second phase of the study will determine whether there is still a place for conventional DMARD therapy after failure on methotrexate and prednisone, or whether anti-TNF is the best option for early remission induction treatment," Dr. Allaart says.
For now, she suggests the optimal strategy is to start treatment early and aim at remission. "A short initial course of prednisone, even at a relatively high dose, is probably preferred over delayed but long-term low prednisone dosages in patients with RA," she says. "We found that even with relatively mild or little joint involvement, patients are motivated to take progressive medication in order to achieve early remission."
Patients should talk to their rheumatologists to determine their best course of treatment.
The American College of Rheumatology is an international professional medical society that represents more than 8,000 rheumatologists and rheumatology health professionals around the world. Its mission is to advance rheumatology. The ACR/ARHP Annual Scientific Meeting is the premier meeting in rheumatology.
Editor's Notes: K V C de Boer will present this research during the ACR Annual Scientific Meeting at the Georgia World Congress Center at 3:30 PM on Tuesday, November 9 in the Sidney J. Marcus Auditorium. Dr. Allaart will be available for media questions and briefing at 8:30 AM on Monday, November 8 in the on-site press conference room, B 212.
Learn more about living well with rheumatic disease as well as rheumatologists and the role they play in health care. Also, discover how the ACR Research and Education Foundation's Within Our Reach: Finding a Cure for Rheumatoid Arthritis campaign is accelerating RA research.
Presentation Number: 1396
Induction Therapy with Methotrexate and Prednisone in Rheumatoid or Very Early Arthritic Disease: IMPROVED Study.
K V C de Boer (LUMC, Leiden, Leiden)
K Visser (LUMC, Leiden, Leiden)
H K Ronday (Haga Hospital, the Hague)
A A Schouffoer (Groene Hart Hospital, Gouda)
J H L M Groenendael (Franciscus Hospital, Roosendaal)
A J Peeters (Reinier de Graaf Gasthuis, Delft)
I Speyer (Bronovo Hospital, the Hague)
G Coll?©e (MCH, the Hague)
P B J Sonnaville (Oosterschelde Hospital, Goes)
B A M Grillet (Zorgsaam, Terneuzen)
T. W J Huizinga (LUMC, Leiden, Leiden)
C F Allaart, MD, PhD (LUMC, Leiden, Leiden)
Aim: To assess the rate of remission after 4 months of treatment with methotrexate (MTX) and a tapered high dose prednisone in patients with recent onset rheumatoid or undifferentiated arthritis (RA and UA), in relation to clinical and demographic baseline criteria.
Methods: IMPROVED is a multicenter single blind clinical study in patients with recent onset RA and UA, with an open label induction phase with MTX 25 mg/wk and prednisone 60 mg/day tapered to 7.5 mg/day in 7 weeks, aimed at achieving DAS < 1.6, which will be followed by tapering to drug free if remission persists, or randomization to multi-DMARD or MTX + adalimumab if DAS ?‰? 1.6 after 4 months. To date, 161 patients with UA (arthritis > 1 joint, at risk for developing RA by estimation of a rheumatologist) and 261 patients with recent onset RA (ACR 1987 criteria, symptom duration < two years) were included. Clinical outcomes (% remission DAS
Doctors Should Watch For Depression In Arthritis Patients
Patients with rheumatoid arthritis are twice as likely to experience depression but are unlikely to talk to a doctor about it, according to researchers at the University of North Carolina at Chapel Hill.
Rheumatoid arthritis (RA) the most common form of chronic inflammatory arthritis is a debilitating disease characterized by inflammation of joint tissues, persistent pain, functional disability, stiffness and fatigue.
Betsy Sleath, PhD, a professor at the UNC School of Pharmacy, said that although depression in primary care settings has been well examined, no previous studies have looked at whether rheumatologists and RA patients discuss depression during medical visits.
In a new study lead by Sleath and published in this month's issue of Arthritis Care & Research, researchers found that almost 11 percent of RA patients had moderately severe to severe symptoms of depression. Those who were rated as being more restricted in their normal activities were significantly more likely to have these symptoms.
The study also found that only one in five of the patients who showed symptoms of depression discussed it with their rheumatologists. Those who did were always the ones to bring up the topic, not the physician. When depression was brought up, it was often not discussed at any length.
Sleath said when patients visit their specialist, their arthritis is understandably their main focus but rheumatologists should consider addressing both RA and depression when they see their patients.
"Chronic diseases can greatly affect a patient's psychosocial well-being, and depression can also affect a patient's adherence to treatment regimens," Sleath said. "Since many arthritis patients see their rheumatologist more often then their primary-care physician, we recommend that rheumatologists take steps to screen patients for signs of depression."
Sleath said if physicians are uncomfortable discussing depression with their patients, they should consider having their office staff administer a brief depression screening before the patients' visits in order to identify problems early on.
In addition to screening for depression, Sleath said it is important for patients to have access to appropriate treatment. Rheumatologists can treat the depression themselves, refer patients to a mental health professional or communicate with the patient's primary-care physician to coordinate a treatment plan. Also, given how common depression is in these patients, rheumatology training programs should educate physicians about the importance of screening for and treating depression, she said.
The study included 200 arthritis patients from four rheumatology clinics with eight participating doctors. Patient visits were audiotaped, and patients were interviewed after their medical visits using a questionnaire to assess depressive symptoms.
The study is titled "Communication about Depression during Rheumatoid Arthritis Patient Visits." The other authors of the study are Betty Chewning, PhD, of the University of Wisconsin; Gail Tudor, PhD, from Husson College in Bangor, Maine; Brenda M. De Vellis, PhD, and Robert F. De Vellis, PhD, professors of health behavior and health education in the UNC School of Public Health; Morris Weinberger, PhD, the Vergil N. Slee Distinguished Professor of Healthcare Quality Management and the director of the doctoral program in the UNC School of Public Health's health policy and administration department; and Ashley Beard, a PhD candidate at the UNC School of Pharmacy.
University of North Carolina at Chapel Hill
210 Pittsboro St. Campus Box 6210
Chapel Hill, NC 27514
United States
unc
Rheumatoid arthritis (RA) the most common form of chronic inflammatory arthritis is a debilitating disease characterized by inflammation of joint tissues, persistent pain, functional disability, stiffness and fatigue.
Betsy Sleath, PhD, a professor at the UNC School of Pharmacy, said that although depression in primary care settings has been well examined, no previous studies have looked at whether rheumatologists and RA patients discuss depression during medical visits.
In a new study lead by Sleath and published in this month's issue of Arthritis Care & Research, researchers found that almost 11 percent of RA patients had moderately severe to severe symptoms of depression. Those who were rated as being more restricted in their normal activities were significantly more likely to have these symptoms.
The study also found that only one in five of the patients who showed symptoms of depression discussed it with their rheumatologists. Those who did were always the ones to bring up the topic, not the physician. When depression was brought up, it was often not discussed at any length.
Sleath said when patients visit their specialist, their arthritis is understandably their main focus but rheumatologists should consider addressing both RA and depression when they see their patients.
"Chronic diseases can greatly affect a patient's psychosocial well-being, and depression can also affect a patient's adherence to treatment regimens," Sleath said. "Since many arthritis patients see their rheumatologist more often then their primary-care physician, we recommend that rheumatologists take steps to screen patients for signs of depression."
Sleath said if physicians are uncomfortable discussing depression with their patients, they should consider having their office staff administer a brief depression screening before the patients' visits in order to identify problems early on.
In addition to screening for depression, Sleath said it is important for patients to have access to appropriate treatment. Rheumatologists can treat the depression themselves, refer patients to a mental health professional or communicate with the patient's primary-care physician to coordinate a treatment plan. Also, given how common depression is in these patients, rheumatology training programs should educate physicians about the importance of screening for and treating depression, she said.
The study included 200 arthritis patients from four rheumatology clinics with eight participating doctors. Patient visits were audiotaped, and patients were interviewed after their medical visits using a questionnaire to assess depressive symptoms.
The study is titled "Communication about Depression during Rheumatoid Arthritis Patient Visits." The other authors of the study are Betty Chewning, PhD, of the University of Wisconsin; Gail Tudor, PhD, from Husson College in Bangor, Maine; Brenda M. De Vellis, PhD, and Robert F. De Vellis, PhD, professors of health behavior and health education in the UNC School of Public Health; Morris Weinberger, PhD, the Vergil N. Slee Distinguished Professor of Healthcare Quality Management and the director of the doctoral program in the UNC School of Public Health's health policy and administration department; and Ashley Beard, a PhD candidate at the UNC School of Pharmacy.
University of North Carolina at Chapel Hill
210 Pittsboro St. Campus Box 6210
Chapel Hill, NC 27514
United States
unc
Bad Mix Of Bacterial Remnants And Genetics Leads To Arthritis
Here's another reason to hate leftovers. A research study appearing in the April 2009 issue of the Journal of Leukocyte Biology sheds light on one cause of arthritis: bacteria. In the study, scientists from the United States and The Netherlands show that a specific gene called NOD2 triggers arthritis or makes it worse when leftover remnants of bacteria cell walls, called muramyl dipeptide or MDP, are present. This discovery offers an important first step toward new treatments to prevent or lessen the symptoms of inflammatory arthritis.
"Despite recent advances in the treatment of arthritis, none target its cause," said Michael Davey, Associate Chief of Staff for Research at the Portland Oregon Veteran's Affairs Medical Center and one of the researchers involved in the study. "Our work with MDP and NOD2 is a step toward understanding the root cause of arthritis which one day may allow certain forms of arthritis to be prevented altogether."
Davey and colleagues made this discovery through experiments using two groups of mice, one group was normal and the other had been genetically modified so that their NOD2 gene was deactivated (commonly referred to as "knocked out"). Then they administered MDP to the joints of mice in each group, and unlike the normal group of mice, the mice with the deactivated NOD2 gene did not experience signs of arthritis. This may also be an important advance in the understanding and treatment of Blau Syndrome, a rare genetic disease characterized by granulomatous arthritis (arthritis caused by bacteria), uveitis (inflammation in the middle layer of the eye), skin rash and cranial neuropathy (a disorder affecting nerves that control sight, eye movement, hearing, and taste).
"Now that we know that bacterial products can activate this NOD2 pathway and that this signal contributes to arthritis," said John Wherry, Ph.D., Deputy Editor of the Journal of Leukocyte Biology, "the next step is to find treatments that either rid the body of this inflammatory signal or mask it. Either way, the net effect would be the same: people would be spared from a very crippling disease. "
According to the U.S Centers for Disease Control and Prevention more that 40 million American say that they have been told by a doctor that they have arthritis or another rheumatic condition. Arthritis is the most common cause of disability in the United States and limits activities of nearly 19 million people.
Notes:
The Journal of Leukocyte Biology publishes peer-reviewed manuscripts on original investigations focusing on the cellular and molecular biology of leukocytes and on the origins, the developmental biology, biochemistry and functions of granulocytes, lymphocytes, mononuclear phagocytes and other cells involved in host defense and inflammation. The Journal of Leukocyte Biology is published by the Society for Leukocyte Biology.
Article Details: H. L. Rosenzweig, M. M. Jann, T. T. Glant, T. M. Martin, S. R. Planck, W. van Eden, P. J. S. van Kooten, R. A. Flavell, K. S. Kobayashi, J. T. Rosenbaum, and M. P. Davey. Activation of nucleotide oligomerization domain 2 exacerbates a murine model of proteoglycan-induced arthritis. J Leukoc Biol 2009 85: 711 - Abstract.
Source:
Cody Mooneyhan
Federation of American Societies for Experimental Biology
"Despite recent advances in the treatment of arthritis, none target its cause," said Michael Davey, Associate Chief of Staff for Research at the Portland Oregon Veteran's Affairs Medical Center and one of the researchers involved in the study. "Our work with MDP and NOD2 is a step toward understanding the root cause of arthritis which one day may allow certain forms of arthritis to be prevented altogether."
Davey and colleagues made this discovery through experiments using two groups of mice, one group was normal and the other had been genetically modified so that their NOD2 gene was deactivated (commonly referred to as "knocked out"). Then they administered MDP to the joints of mice in each group, and unlike the normal group of mice, the mice with the deactivated NOD2 gene did not experience signs of arthritis. This may also be an important advance in the understanding and treatment of Blau Syndrome, a rare genetic disease characterized by granulomatous arthritis (arthritis caused by bacteria), uveitis (inflammation in the middle layer of the eye), skin rash and cranial neuropathy (a disorder affecting nerves that control sight, eye movement, hearing, and taste).
"Now that we know that bacterial products can activate this NOD2 pathway and that this signal contributes to arthritis," said John Wherry, Ph.D., Deputy Editor of the Journal of Leukocyte Biology, "the next step is to find treatments that either rid the body of this inflammatory signal or mask it. Either way, the net effect would be the same: people would be spared from a very crippling disease. "
According to the U.S Centers for Disease Control and Prevention more that 40 million American say that they have been told by a doctor that they have arthritis or another rheumatic condition. Arthritis is the most common cause of disability in the United States and limits activities of nearly 19 million people.
Notes:
The Journal of Leukocyte Biology publishes peer-reviewed manuscripts on original investigations focusing on the cellular and molecular biology of leukocytes and on the origins, the developmental biology, biochemistry and functions of granulocytes, lymphocytes, mononuclear phagocytes and other cells involved in host defense and inflammation. The Journal of Leukocyte Biology is published by the Society for Leukocyte Biology.
Article Details: H. L. Rosenzweig, M. M. Jann, T. T. Glant, T. M. Martin, S. R. Planck, W. van Eden, P. J. S. van Kooten, R. A. Flavell, K. S. Kobayashi, J. T. Rosenbaum, and M. P. Davey. Activation of nucleotide oligomerization domain 2 exacerbates a murine model of proteoglycan-induced arthritis. J Leukoc Biol 2009 85: 711 - Abstract.
Source:
Cody Mooneyhan
Federation of American Societies for Experimental Biology
How Antibodies Block The S1P Receptor On T Cells Has Potential To Stop Autoimmune Diseases And Transplant Rejection
After several years of battling recurring infections, the last thing a patient and her doctors ever expected was that the cause of her problems might actually help millions live longer, more active lives. Now, researchers have high hopes because Edward Goetzl and his colleagues from the University of California and The Ohio State University discovered that the patient made a unique antibody to her own T cells, the cells that mediate much of autoimmunity. Acting on the surface of T cells via a novel mechanism, the antibody reduced the number of T cells in her blood stream: a result that usually requires a host of "immunosuppressive" and possibly toxic drugs. Their research discovery, published online in The FASEB Journal, may lead to entirely new therapies for a wide range of autoimmune disorders, such as colitis, lupus, rheumatoid arthritis, inflammatory bowel disease, and multiple sclerosis, as well as new ways to prevent transplant rejection.
"The possibility that these antibodies can be used to treat diverse autoimmune diseases with minimal risk of infections represents a new horizon for reversing these disabling and often fatal conditions," said Edward Goetzl, a senior researcher involved in the study.
In the research report, Goetzl and colleagues explain how they discovered that the antibodies produced by this patient blocked the sphingosine 1-phosphate (S1P) receptor on T cells. The S1P receptor is a cell-surface antenna that receives signals telling T cells to leave the lymph nodes and patrol the body. When this antenna was disabled, the T cells failed to leave the lymph nodes (chemotaxis), reducing their numbers in the bloodstream. Taking this discovery one step further, the researchers created more of the patient's antibodies in the laboratory and gave them to mice with colitis (an autoimmune disorder). After receiving the antibodies, symptoms of colitis were reduced.
"This discovery is very good news for people with autoimmune disorders." said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal "It also shows that when modern scientists work out exactly what is wrong with one patient they can come up with unexpected new ways to treat many thousands.
The FASEB Journal (fasebj) is published by the Federation of American Societies for Experimental Biology (FASEB) and is the most cited biology journal worldwide according to the Institute for Scientific Information. FASEB comprises 22 nonprofit societies with more than 80,000 members, making it the largest coalition of biomedical research associations in the United States. FASEB advances biological science through collaborative advocacy for research policies that promote scientific progress and education and lead to improvements in human health.
Source: Cody Mooneyhan
Federation of American Societies for Experimental Biology
"The possibility that these antibodies can be used to treat diverse autoimmune diseases with minimal risk of infections represents a new horizon for reversing these disabling and often fatal conditions," said Edward Goetzl, a senior researcher involved in the study.
In the research report, Goetzl and colleagues explain how they discovered that the antibodies produced by this patient blocked the sphingosine 1-phosphate (S1P) receptor on T cells. The S1P receptor is a cell-surface antenna that receives signals telling T cells to leave the lymph nodes and patrol the body. When this antenna was disabled, the T cells failed to leave the lymph nodes (chemotaxis), reducing their numbers in the bloodstream. Taking this discovery one step further, the researchers created more of the patient's antibodies in the laboratory and gave them to mice with colitis (an autoimmune disorder). After receiving the antibodies, symptoms of colitis were reduced.
"This discovery is very good news for people with autoimmune disorders." said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal "It also shows that when modern scientists work out exactly what is wrong with one patient they can come up with unexpected new ways to treat many thousands.
The FASEB Journal (fasebj) is published by the Federation of American Societies for Experimental Biology (FASEB) and is the most cited biology journal worldwide according to the Institute for Scientific Information. FASEB comprises 22 nonprofit societies with more than 80,000 members, making it the largest coalition of biomedical research associations in the United States. FASEB advances biological science through collaborative advocacy for research policies that promote scientific progress and education and lead to improvements in human health.
Source: Cody Mooneyhan
Federation of American Societies for Experimental Biology
Alpine Mountaineer And Alzheimer's Advocate To Climb Highest Peak On Each Continent To Raise Awareness Of Growing Prevalence And Burden Of Alzheimer's
Alpine mountaineer and Alzheimer's disease advocate Alan Arnette will embark later this month to climb the 7 Summits, the highest peak on each continent. This ambitious year-long climbing campaign The 7 Summits Climb for Alzheimer's: Memories are Everything aims to raise awareness of the growing Alzheimer's prevalence in our aging population and the enormous financial and personal burden it places on people with the disease, their caregivers and society.
"The mental and physical demands of scaling seemingly insurmountable peaks are not unlike the everyday challenges faced by those living with Alzheimer's disease and their caregivers," said Mr. Arnette, who cared for his mother with Alzheimer's until her death last year. "Both involve understanding personal limitations, reaching out for support and taking steps daily on a very long road."
Alzheimer's, the nation's 6th most deadly disease, robs individuals of collected memories, corrupts their distinct and true personalities and makes them unable to function independently. The burden of caring for these patients often falls to family members. In the United States, an estimated 10.9 million unpaid caregivers see to the daily needs of people struck by Alzheimer's. Last year, these caregivers provided about 12.5 billion hours of care.
Mr. Arnette, who has been mountain climbing since he was 38, retired from his job with a leading technology company to care for his mother, Ida, who has since died from Alzheimer's. Since then, the 54-year-old advocate has worked tirelessly to inspire people to join his efforts to help raise $1 million to advance Alzheimer's research.
The Alzheimer's Immunotherapy Program of Janssen Alzheimer Immunotherapy and Pfizer Inc. (NYSE: PFE) is funding Mr. Arnette's climbs. All money Mr. Arnette raises from donations will go directly to the organization he selected, the Cure Alzheimer's Fund™, for research. International Mountain Guides is also supporting Mr. Arnette's efforts.
"As a former caregiver for his mother, Alan understands the burden of Alzheimer's and the needs of patients and caregivers who are devastated by the disease. "His efforts to embark on this incredible journey are an inspiration to Alzheimer's patients, caregivers and beyond," said Gregory Rippon, MD, MS, Disease Area Medical Lead, Specialty Neuroscience, Clinical Development & Medical Affairs, Pfizer, on behalf of the Alzheimer's Immunotherapy Program. "We are proud to support Alan Arnette's efforts to advance education and research to help fight this disease."
Every 70 Seconds, Someone is Diagnosed With Alzheimer's
Alzheimer's disease is the 6th leading cause of death in the United States, with another person newly diagnosed every 70 seconds. It has been estimated to affect more than 5 million Americans and more than 25 million people worldwide. The lack of awareness around dementia is a global problem, leading to misunderstandings of Alzheimer's disease. Alzheimer's disease is not a normal part of aging and gradually destroys a person's memory and their ability to learn, reason, make judgments, communicate and carry out basic daily activities like bathing and eating. As there is neither a cure nor a treatment that addresses the underlying cause of Alzheimer's, there remains a significant need to advance treatment options that change the course of Alzheimer's, improve patient outcomes and reduce the burden on caregivers.
The indirect and direct costs of caring for people with Alzheimer's disease is estimated to be more than $100 billion a year in the United States alone. The worldwide costs of dementia are estimated to exceed one percent of global gross domestic product (GDP) in 2010, which equates to $600 billion, further demonstrating the global prevalence of the disease.
"Research is the key to solving the complexities of Alzheimer's disease and Alan Arnette's courageous fundraising efforts will help the Alzheimer's community come one step closer to finding a cure," said Tim Armour, President of the Cure Alzheimer's Fund™.
The Summits
Mr. Arnette, a resident of Colorado, departs on the first climb of his seven climbs on November 24, 2010. The first peak is the 16,067-foot (4897 meter) Mt. Vinson Massif in Antarctica. By December 2011, he intends to reach the summits of:
-- Aconcagua, Argentina, South America - 22,841ft/6962m
-- Everest, Nepal, Asia - 29,035ft/8850m
-- Denali, Alaska, North America - 20,320ft/6194m
-- Elbrus, Russia, Europe - 18,481ft/5633m
-- Kilimanjaro, Tanzania, Africa - 19,340ft/5896m
-- Carstensz Pyramid, Indonesia, Oceania - 16,023ft/4884m
Mr. Arnette is taking on the extended challenge of climbing an eighth mountain, Mt. Kosciuszko in Australia, which is part of the Oceania continent.
Alzheimer's Immunotherapy Program
The Alzheimer's Immunotherapy Program of Janssen Alzheimer Immunotherapy and Pfizer Inc. is an equal collaboration committed to researching and developing selective products for the treatment and/or prevention of neurodegenerative conditions, including Alzheimer's disease.
The Alzheimer's Immunotherapy Program believes that it is possible to reduce the burden of disease through early intervention in the illness. It is dedicated to delivering comprehensive and integrated solutions that help address the needs of people impacted by Alzheimer's disease.
Its research focuses on the beta amyloid hypothesis. Scientific evidence supports the idea that preventing the accumulation and/or promoting the removal of beta-amyloid may have the potential to slow the progression of Alzheimer's disease and help preserve function in people with the disease. This theory is being tested in clinical trials.
Source: Pfizer Inc
"The mental and physical demands of scaling seemingly insurmountable peaks are not unlike the everyday challenges faced by those living with Alzheimer's disease and their caregivers," said Mr. Arnette, who cared for his mother with Alzheimer's until her death last year. "Both involve understanding personal limitations, reaching out for support and taking steps daily on a very long road."
Alzheimer's, the nation's 6th most deadly disease, robs individuals of collected memories, corrupts their distinct and true personalities and makes them unable to function independently. The burden of caring for these patients often falls to family members. In the United States, an estimated 10.9 million unpaid caregivers see to the daily needs of people struck by Alzheimer's. Last year, these caregivers provided about 12.5 billion hours of care.
Mr. Arnette, who has been mountain climbing since he was 38, retired from his job with a leading technology company to care for his mother, Ida, who has since died from Alzheimer's. Since then, the 54-year-old advocate has worked tirelessly to inspire people to join his efforts to help raise $1 million to advance Alzheimer's research.
The Alzheimer's Immunotherapy Program of Janssen Alzheimer Immunotherapy and Pfizer Inc. (NYSE: PFE) is funding Mr. Arnette's climbs. All money Mr. Arnette raises from donations will go directly to the organization he selected, the Cure Alzheimer's Fund™, for research. International Mountain Guides is also supporting Mr. Arnette's efforts.
"As a former caregiver for his mother, Alan understands the burden of Alzheimer's and the needs of patients and caregivers who are devastated by the disease. "His efforts to embark on this incredible journey are an inspiration to Alzheimer's patients, caregivers and beyond," said Gregory Rippon, MD, MS, Disease Area Medical Lead, Specialty Neuroscience, Clinical Development & Medical Affairs, Pfizer, on behalf of the Alzheimer's Immunotherapy Program. "We are proud to support Alan Arnette's efforts to advance education and research to help fight this disease."
Every 70 Seconds, Someone is Diagnosed With Alzheimer's
Alzheimer's disease is the 6th leading cause of death in the United States, with another person newly diagnosed every 70 seconds. It has been estimated to affect more than 5 million Americans and more than 25 million people worldwide. The lack of awareness around dementia is a global problem, leading to misunderstandings of Alzheimer's disease. Alzheimer's disease is not a normal part of aging and gradually destroys a person's memory and their ability to learn, reason, make judgments, communicate and carry out basic daily activities like bathing and eating. As there is neither a cure nor a treatment that addresses the underlying cause of Alzheimer's, there remains a significant need to advance treatment options that change the course of Alzheimer's, improve patient outcomes and reduce the burden on caregivers.
The indirect and direct costs of caring for people with Alzheimer's disease is estimated to be more than $100 billion a year in the United States alone. The worldwide costs of dementia are estimated to exceed one percent of global gross domestic product (GDP) in 2010, which equates to $600 billion, further demonstrating the global prevalence of the disease.
"Research is the key to solving the complexities of Alzheimer's disease and Alan Arnette's courageous fundraising efforts will help the Alzheimer's community come one step closer to finding a cure," said Tim Armour, President of the Cure Alzheimer's Fund™.
The Summits
Mr. Arnette, a resident of Colorado, departs on the first climb of his seven climbs on November 24, 2010. The first peak is the 16,067-foot (4897 meter) Mt. Vinson Massif in Antarctica. By December 2011, he intends to reach the summits of:
-- Aconcagua, Argentina, South America - 22,841ft/6962m
-- Everest, Nepal, Asia - 29,035ft/8850m
-- Denali, Alaska, North America - 20,320ft/6194m
-- Elbrus, Russia, Europe - 18,481ft/5633m
-- Kilimanjaro, Tanzania, Africa - 19,340ft/5896m
-- Carstensz Pyramid, Indonesia, Oceania - 16,023ft/4884m
Mr. Arnette is taking on the extended challenge of climbing an eighth mountain, Mt. Kosciuszko in Australia, which is part of the Oceania continent.
Alzheimer's Immunotherapy Program
The Alzheimer's Immunotherapy Program of Janssen Alzheimer Immunotherapy and Pfizer Inc. is an equal collaboration committed to researching and developing selective products for the treatment and/or prevention of neurodegenerative conditions, including Alzheimer's disease.
The Alzheimer's Immunotherapy Program believes that it is possible to reduce the burden of disease through early intervention in the illness. It is dedicated to delivering comprehensive and integrated solutions that help address the needs of people impacted by Alzheimer's disease.
Its research focuses on the beta amyloid hypothesis. Scientific evidence supports the idea that preventing the accumulation and/or promoting the removal of beta-amyloid may have the potential to slow the progression of Alzheimer's disease and help preserve function in people with the disease. This theory is being tested in clinical trials.
Source: Pfizer Inc
Voltaren Gel Receives US Regulatory Approval As The First Approved Topical Prescription Treatment For Pain Associated With Osteoarthritis
Voltaren Gel (diclofenac sodium topical gel) 1% has received US regulatory approval as the first topical prescription treatment that patients can apply directly to sites of pain associated with osteoarthritis.
The US Food and Drug Administration (FDA) granted the approval for Voltaren Gel, which is a non-steroidal anti-inflammatory (NSAID) medication, for use in treating pain associated with osteoarthritis in joints amenable to topical treatment, such as the knees and those of the hands.
Osteoarthritis is a chronic condition characterized by the breakdown of cartilage in the joint.
Clinical trials have demonstrated Voltaren Gel to be highly effective in treating osteoarthritis pain in the hands and knees, which are the body's most commonly affected joints. It is the first topical osteoarthritis treatment to have proven its effectiveness in both the hands and knees through clinical trials.
Voltaren Gel, which will be marketed in the US by the OTC business unit since this is the case in many other countries, delivers effective pain relief with a favorable safety profile as its systemic absorption is 94% less than the comparable oral diclofenac treatment.
"Voltaren Gel is proven to be effective for osteoarthritis of the hand and knee and has a favorable safety profile. The combination of benefit and safety provides a welcome new treatment approach for osteoarthritis, offering patients an alternative to oral therapies," said Roy Altman, MD, Professor of Medicine in the Division of Rheumatology and Immunology at UCLA in Los Angeles and Past President of the Osteoarthritis Research Society International. "Voltaren Gel delivers the proven efficacy of diclofenac with significantly less systemic absorption, minimizing the risk of side effects."
The efficacy and safety of Voltaren Gel were studied in more than 900 patients with knee or hand osteoarthritis. The US approval was based on several studies, including the results of two randomized, double-blind, placebo-controlled efficacy studies and a 12-month safety study.
Voltaren Gel was shown to significantly reduce pain in hand and knee osteoarthritis, with pain relief sustained through the end of treatment. After six weeks of treatment in an efficacy study of patients with osteoarthritis of the hand, results showed that pain levels were reduced by nearly half (46%). In a 12-week study in patients with osteoarthritis of the knee, Voltaren Gel showed a 51% reduction in pain.
"Voltaren Gel represents an important clinical milestone - it is the first prescription topical treatment in the US shown to relieve osteoarthritis pain and to clinically prove efficacy in treating both the knees and hands," said Jorge Insuasty, MD, Senior Vice President, Research and Development in the Group's OTC business unit. "Patients now have the option to effectively treat osteoarthritis pain at the source with favorable tolerability."
Approximately 21 million people in the US have osteoarthritis,[1] and the aging population in the US means 72 million more will be at risk for developing the condition by 2030.[2] Osteoarthritis is a chronic, painful condition that often leads to working limitations and reduced overall health.[3]
About osteoarthritis
Osteoarthritis is a chronic condition characterized by the breakdown of cartilage in the joint. Cartilage cushions the ends of the bones in joints - such as knees, hands, elbows, wrists, ankles and feet - which allows for easy movement. When cartilage erodes, bones can rub together, resulting in pain and loss of free movement in the joint.[3] The most common symptoms include pain, joint soreness, stiffness and deterioration of overall coordination, posture and walking.
Arthritis and related conditions, such as osteoarthritis, cost the US economy nearly USD 128 billion per year in medical care and indirect expenses, including lost wages and production.[4]
Despite the high prevalence of osteoarthritis, there is no cure for this disease, which tends to progressively reduce mobility and the overall health state in the affected patients.
About Voltaren Gel
Voltaren Gel provides 1% diclofenac sodium in a topical gel formulation. It is a non-steroidal anti-inflammatory (NSAID) medication indicated for the pain of osteoarthritis in joints amenable to topical treatment, such as the knees and those of the hands. Voltaren Gel delivers highly effective pain relief with a favorable safety profile as its systemic absorption is 94% less than comparable oral diclofenac treatment.
Important safety information
The most common adverse reactions reported in Voltaren Gel clinical trials were application site reactions in 7% of treated patients. With all NSAIDs there may be an increased risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, which can be fatal. NSAIDs cause an increased risk of serious gastrointestinal adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. The use of Voltaren Gel is contraindicated in patients with a known hypersensitivity to diclofenac. Voltaren Gel should not be administered to patients who have experienced asthma, urticaria or other allergic-type reactions after taking aspirin or other NSAIDs. Severe, rarely fatal, anaphylactic-like reactions to NSAIDs have been reported in such patients. Voltaren Gel is contraindicated for the treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery.
Voltaren Gel should not be used in combination with other oral NSAIDs or aspirin because of the potential for increased adverse effects. Similarly, combined use of Voltaren Gel with other topical products, such as sunscreens and cosmetics, on the same skin area has not been tested and should be avoided because of the potential to alter local tolerability and absorption.
Disclaimer
The foregoing release contains forward-looking statements that can be identified by terminology such as "will," "often leads to," "may be," "can be," or similar expressions, or by express or implied discussions regarding potential future revenues from Voltaren Gel. Such forward-looking statements reflect the current views of the Company regarding future events, and involve known and unknown risks, uncertainties and other factors that may cause actual results to be materially different from any future results, performance or achievements expressed or implied by such statements. There can be no guarantee that Voltaren Gel will achieve any particular levels of revenue in the future. In particular, management's expectations regarding commercialization of Voltaren Gel could be affected by, among other things, unexpected clinical trial results, including unexpected new clinical data and unexpected additional analysis of existing clinical data, competition in general, increased government, industry and general public pricing pressures, unexpected regulatory actions or delays or government regulation generally, and other risks and factors referred to in Novartis AG's current Form 20-F on file with the U.S. Securities and Exchange Commission. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those anticipated, believed, estimated or expected. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise.
About Novartis
Novartis AG (NYSE: NVS) is a world leader in offering medicines to protect health, cure disease and improve well-being. Our goal is to discover, develop and successfully market innovative products to treat patients, ease suffering and enhance the quality of life. We are strengthening our medicine-based portfolio, which is focused on strategic growth platforms in innovation-driven pharmaceuticals, high-quality and low-cost generics, human vaccines and leading self-medication OTC brands. Novartis is the only company with leadership positions in these areas. In 2006, the Group's businesses achieved net sales of USD 37.0 billion and net income of USD 7.2 billion. Approximately USD 5.4 billion was invested in R&D. Headquartered in Basel, Switzerland, Novartis Group companies employ approximately 100,000 associates and operate in over 140 countries around the world. For more information, please visit our website at novartis.
References
[1] U.S. Centers for Disease Control and Prevention (CDC). Arthritis Related Statistics. Available at: cdc/arthritis/data_statistics/arthritis_related_statistics.htm. Accessed on October 17, 2007.
[2] National Institute of Arthritis Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health, U.S. Department of Health and Human Services. Handout on Health: Osteoarthritis. Available at: niams.nih/health_info/Osteoarthritis/default.asp. Accessed on October 17, 2007.
[3] Arthritis Foundation. Available at: arthritis. Accessed on October 17, 2007.
[4] U.S. Centers for Disease Control and Prevention (CDC). [CDC (2007) Update: National and State Medical Expenditures and Lost Earnings Attributable to Arthritis and Other Rheumatic Conditions-United States, 2003. MMWR Morb Mortal Wkly Rep, 56(01):4-7].
The US Food and Drug Administration (FDA) granted the approval for Voltaren Gel, which is a non-steroidal anti-inflammatory (NSAID) medication, for use in treating pain associated with osteoarthritis in joints amenable to topical treatment, such as the knees and those of the hands.
Osteoarthritis is a chronic condition characterized by the breakdown of cartilage in the joint.
Clinical trials have demonstrated Voltaren Gel to be highly effective in treating osteoarthritis pain in the hands and knees, which are the body's most commonly affected joints. It is the first topical osteoarthritis treatment to have proven its effectiveness in both the hands and knees through clinical trials.
Voltaren Gel, which will be marketed in the US by the OTC business unit since this is the case in many other countries, delivers effective pain relief with a favorable safety profile as its systemic absorption is 94% less than the comparable oral diclofenac treatment.
"Voltaren Gel is proven to be effective for osteoarthritis of the hand and knee and has a favorable safety profile. The combination of benefit and safety provides a welcome new treatment approach for osteoarthritis, offering patients an alternative to oral therapies," said Roy Altman, MD, Professor of Medicine in the Division of Rheumatology and Immunology at UCLA in Los Angeles and Past President of the Osteoarthritis Research Society International. "Voltaren Gel delivers the proven efficacy of diclofenac with significantly less systemic absorption, minimizing the risk of side effects."
The efficacy and safety of Voltaren Gel were studied in more than 900 patients with knee or hand osteoarthritis. The US approval was based on several studies, including the results of two randomized, double-blind, placebo-controlled efficacy studies and a 12-month safety study.
Voltaren Gel was shown to significantly reduce pain in hand and knee osteoarthritis, with pain relief sustained through the end of treatment. After six weeks of treatment in an efficacy study of patients with osteoarthritis of the hand, results showed that pain levels were reduced by nearly half (46%). In a 12-week study in patients with osteoarthritis of the knee, Voltaren Gel showed a 51% reduction in pain.
"Voltaren Gel represents an important clinical milestone - it is the first prescription topical treatment in the US shown to relieve osteoarthritis pain and to clinically prove efficacy in treating both the knees and hands," said Jorge Insuasty, MD, Senior Vice President, Research and Development in the Group's OTC business unit. "Patients now have the option to effectively treat osteoarthritis pain at the source with favorable tolerability."
Approximately 21 million people in the US have osteoarthritis,[1] and the aging population in the US means 72 million more will be at risk for developing the condition by 2030.[2] Osteoarthritis is a chronic, painful condition that often leads to working limitations and reduced overall health.[3]
About osteoarthritis
Osteoarthritis is a chronic condition characterized by the breakdown of cartilage in the joint. Cartilage cushions the ends of the bones in joints - such as knees, hands, elbows, wrists, ankles and feet - which allows for easy movement. When cartilage erodes, bones can rub together, resulting in pain and loss of free movement in the joint.[3] The most common symptoms include pain, joint soreness, stiffness and deterioration of overall coordination, posture and walking.
Arthritis and related conditions, such as osteoarthritis, cost the US economy nearly USD 128 billion per year in medical care and indirect expenses, including lost wages and production.[4]
Despite the high prevalence of osteoarthritis, there is no cure for this disease, which tends to progressively reduce mobility and the overall health state in the affected patients.
About Voltaren Gel
Voltaren Gel provides 1% diclofenac sodium in a topical gel formulation. It is a non-steroidal anti-inflammatory (NSAID) medication indicated for the pain of osteoarthritis in joints amenable to topical treatment, such as the knees and those of the hands. Voltaren Gel delivers highly effective pain relief with a favorable safety profile as its systemic absorption is 94% less than comparable oral diclofenac treatment.
Important safety information
The most common adverse reactions reported in Voltaren Gel clinical trials were application site reactions in 7% of treated patients. With all NSAIDs there may be an increased risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, which can be fatal. NSAIDs cause an increased risk of serious gastrointestinal adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. The use of Voltaren Gel is contraindicated in patients with a known hypersensitivity to diclofenac. Voltaren Gel should not be administered to patients who have experienced asthma, urticaria or other allergic-type reactions after taking aspirin or other NSAIDs. Severe, rarely fatal, anaphylactic-like reactions to NSAIDs have been reported in such patients. Voltaren Gel is contraindicated for the treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery.
Voltaren Gel should not be used in combination with other oral NSAIDs or aspirin because of the potential for increased adverse effects. Similarly, combined use of Voltaren Gel with other topical products, such as sunscreens and cosmetics, on the same skin area has not been tested and should be avoided because of the potential to alter local tolerability and absorption.
Disclaimer
The foregoing release contains forward-looking statements that can be identified by terminology such as "will," "often leads to," "may be," "can be," or similar expressions, or by express or implied discussions regarding potential future revenues from Voltaren Gel. Such forward-looking statements reflect the current views of the Company regarding future events, and involve known and unknown risks, uncertainties and other factors that may cause actual results to be materially different from any future results, performance or achievements expressed or implied by such statements. There can be no guarantee that Voltaren Gel will achieve any particular levels of revenue in the future. In particular, management's expectations regarding commercialization of Voltaren Gel could be affected by, among other things, unexpected clinical trial results, including unexpected new clinical data and unexpected additional analysis of existing clinical data, competition in general, increased government, industry and general public pricing pressures, unexpected regulatory actions or delays or government regulation generally, and other risks and factors referred to in Novartis AG's current Form 20-F on file with the U.S. Securities and Exchange Commission. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those anticipated, believed, estimated or expected. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise.
About Novartis
Novartis AG (NYSE: NVS) is a world leader in offering medicines to protect health, cure disease and improve well-being. Our goal is to discover, develop and successfully market innovative products to treat patients, ease suffering and enhance the quality of life. We are strengthening our medicine-based portfolio, which is focused on strategic growth platforms in innovation-driven pharmaceuticals, high-quality and low-cost generics, human vaccines and leading self-medication OTC brands. Novartis is the only company with leadership positions in these areas. In 2006, the Group's businesses achieved net sales of USD 37.0 billion and net income of USD 7.2 billion. Approximately USD 5.4 billion was invested in R&D. Headquartered in Basel, Switzerland, Novartis Group companies employ approximately 100,000 associates and operate in over 140 countries around the world. For more information, please visit our website at novartis.
References
[1] U.S. Centers for Disease Control and Prevention (CDC). Arthritis Related Statistics. Available at: cdc/arthritis/data_statistics/arthritis_related_statistics.htm. Accessed on October 17, 2007.
[2] National Institute of Arthritis Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health, U.S. Department of Health and Human Services. Handout on Health: Osteoarthritis. Available at: niams.nih/health_info/Osteoarthritis/default.asp. Accessed on October 17, 2007.
[3] Arthritis Foundation. Available at: arthritis. Accessed on October 17, 2007.
[4] U.S. Centers for Disease Control and Prevention (CDC). [CDC (2007) Update: National and State Medical Expenditures and Lost Earnings Attributable to Arthritis and Other Rheumatic Conditions-United States, 2003. MMWR Morb Mortal Wkly Rep, 56(01):4-7].
Seminal Finding Has Major Implications For The Development Of New And Better Vaccines
A research team led by the La Jolla Institute for Allergy & Immunology has identified the specific gene which triggers the body to produce disease-fighting antibodies -- a seminal finding that clarifies the exact molecular steps taken by the body to mount an antibody defense against viruses and other pathogens. The finding, published online today in the prestigious journal Science, has major implications for the development of new and more effective vaccines. The La Jolla Institute's Shane Crotty, Ph.D., was the lead scientist on the team, which also included researchers from Yale University.
"The finding is enormous in terms of its long-term benefit to science and society as a whole because it illuminates a pivotal piece of the vaccine development puzzle -- that is, 'what is the molecular switch that tells the body to create antibodies?' Dr. Crotty has pinpointed the BCL6 gene and, in doing so, has answered a critical question that has long been sought by the scientific community," said Mitchell Kronenberg, Ph.D., president & scientific director of the La Jolla Institute, a nonprofit biomedical research institute. Dr. Kronenberg said this knowledge opens the door to developing ways to boost antibody production, thereby creating stronger and more effective vaccines.
Rafi Ahmed, Ph.D., director of the Emory Vaccine Center, and a professor of microbiology and immunology at the Emory University School of Medicine, called the finding an "important breakthrough."
"Dr. Crotty has defined the gene that regulates the formation of certain CD4 T cells," said Dr. Ahmed. "Those cells are very critical for antibody production, so describing what regulates the birth of those cells is clearly an important discovery."
Pamela L. Schwartzberg, M.D., Ph.D., a senior investigator in the Cell Signaling Section of the National Human Genome Research Institute, part of the National Institutes of Health, called the discovery a major step forward in the area of vaccine development. "This finding defines the master regulator (gene) that triggers an elaborate cellular interaction necessary to get effective long-term antibody responses, which are required for most successful vaccines," she said. "In making this discovery, Dr. Crotty and his fellow researchers at Yale have made a major contribution that will help provide critical insight into the processes important for successful vaccination and effective immune responses."
The finding is outlined in a paper entitled, "Bcl6 and Blimp-1 are reciprocal and antagonistic regulators of T follicular helper (TFH) cell differentiation." Yale scientist Joseph Craft, M.D., led the Yale research team, which contributed to the study.
Antibodies, Dr. Kronenberg explained, may be thought of as the body's smart bombs, which seek out infectious agents and tag them for destruction. Twenty-five human vaccines currently exist worldwide, 23 of those work by triggering the production of antibodies. "The scientific community has known for many years that antibodies were key to vaccine development and fighting infections," he continued. "But we didn't know exactly how the process worked at the cellular level and it has long been the subject of speculation, debate and intense interest."
Dr. Crotty said it has been well established that antibody production is a multi-step process that involves interactions between several cellular players, key among them CD4 "helper" T cells, which are disease-fighting white blood cells that tell other cells to produce antibodies in response to infections. "There were different flavors of these CD4 helper T cells and, for many years, we, in the scientific community, thought that one of the four varieties of CD4 helper type 2 cells (known as TH-2 cells) triggered the antibody process. But about 10 years ago, scientists realized this was incorrect and that there must exist a fifth variety of CD4 helper T cell that initiated antibody production. It was named TFH."
Dr. Crotty's team set out to understand the inner workings of the TFH pathway. "We discovered that the BCL6 gene was like an on and off switch, or master regulator, in this process. In a series of experiments, we showed that if you turn on this gene, you get more CD4 T helper cells (the TFH type) and it's those cells that are telling the B cells to produce antibodies," he said.
Dr. Crotty's group also tested the finding by using a cellular mechanism to turn off the BCL6 gene. Turning off the gene stopped the production of the TFH cells. "Without this genetic trigger, no TFH cells were produced and consequently no antibodies." The researchers also found that the more TFH cells produced, the greater the antibody response.
Yale researchers, who were collaborators on the study, also tested and proved the finding by deleting the BCL6 gene. "Beautifully, they got the same results - antibody production ceased," said Dr. Crotty.
The finding also may have implications for rheumatoid arthritis and some other autoimmune diseases. "Some autoimmune diseases are triggered by antibody-induced inflammation," said Dr. Crotty. "The ability to turn antibody production off may also offer therapeutic opportunities for these people."
Source:
Bonnie Ward
La Jolla Institute for Allergy and Immunology
"The finding is enormous in terms of its long-term benefit to science and society as a whole because it illuminates a pivotal piece of the vaccine development puzzle -- that is, 'what is the molecular switch that tells the body to create antibodies?' Dr. Crotty has pinpointed the BCL6 gene and, in doing so, has answered a critical question that has long been sought by the scientific community," said Mitchell Kronenberg, Ph.D., president & scientific director of the La Jolla Institute, a nonprofit biomedical research institute. Dr. Kronenberg said this knowledge opens the door to developing ways to boost antibody production, thereby creating stronger and more effective vaccines.
Rafi Ahmed, Ph.D., director of the Emory Vaccine Center, and a professor of microbiology and immunology at the Emory University School of Medicine, called the finding an "important breakthrough."
"Dr. Crotty has defined the gene that regulates the formation of certain CD4 T cells," said Dr. Ahmed. "Those cells are very critical for antibody production, so describing what regulates the birth of those cells is clearly an important discovery."
Pamela L. Schwartzberg, M.D., Ph.D., a senior investigator in the Cell Signaling Section of the National Human Genome Research Institute, part of the National Institutes of Health, called the discovery a major step forward in the area of vaccine development. "This finding defines the master regulator (gene) that triggers an elaborate cellular interaction necessary to get effective long-term antibody responses, which are required for most successful vaccines," she said. "In making this discovery, Dr. Crotty and his fellow researchers at Yale have made a major contribution that will help provide critical insight into the processes important for successful vaccination and effective immune responses."
The finding is outlined in a paper entitled, "Bcl6 and Blimp-1 are reciprocal and antagonistic regulators of T follicular helper (TFH) cell differentiation." Yale scientist Joseph Craft, M.D., led the Yale research team, which contributed to the study.
Antibodies, Dr. Kronenberg explained, may be thought of as the body's smart bombs, which seek out infectious agents and tag them for destruction. Twenty-five human vaccines currently exist worldwide, 23 of those work by triggering the production of antibodies. "The scientific community has known for many years that antibodies were key to vaccine development and fighting infections," he continued. "But we didn't know exactly how the process worked at the cellular level and it has long been the subject of speculation, debate and intense interest."
Dr. Crotty said it has been well established that antibody production is a multi-step process that involves interactions between several cellular players, key among them CD4 "helper" T cells, which are disease-fighting white blood cells that tell other cells to produce antibodies in response to infections. "There were different flavors of these CD4 helper T cells and, for many years, we, in the scientific community, thought that one of the four varieties of CD4 helper type 2 cells (known as TH-2 cells) triggered the antibody process. But about 10 years ago, scientists realized this was incorrect and that there must exist a fifth variety of CD4 helper T cell that initiated antibody production. It was named TFH."
Dr. Crotty's team set out to understand the inner workings of the TFH pathway. "We discovered that the BCL6 gene was like an on and off switch, or master regulator, in this process. In a series of experiments, we showed that if you turn on this gene, you get more CD4 T helper cells (the TFH type) and it's those cells that are telling the B cells to produce antibodies," he said.
Dr. Crotty's group also tested the finding by using a cellular mechanism to turn off the BCL6 gene. Turning off the gene stopped the production of the TFH cells. "Without this genetic trigger, no TFH cells were produced and consequently no antibodies." The researchers also found that the more TFH cells produced, the greater the antibody response.
Yale researchers, who were collaborators on the study, also tested and proved the finding by deleting the BCL6 gene. "Beautifully, they got the same results - antibody production ceased," said Dr. Crotty.
The finding also may have implications for rheumatoid arthritis and some other autoimmune diseases. "Some autoimmune diseases are triggered by antibody-induced inflammation," said Dr. Crotty. "The ability to turn antibody production off may also offer therapeutic opportunities for these people."
Source:
Bonnie Ward
La Jolla Institute for Allergy and Immunology
Natural Compounds That Could Slow Blood Vessel Growth
Using computer models and live cell experiments, biomedical engineers at the Johns Hopkins University School of Medicine have discovered more than 100 human protein fragments that can slow or stop the growth of cells that make up new blood vessels.
Reporting online last week in the Proceedings of the National Academy of Sciences, the researchers say the findings could lead to developing treatments to fight diseases that depend on the growth of new blood vessels, including cancer, macular degeneration and rheumatoid arthritis.
"Before, there were only 40 known antiangiogenesis peptides," says Aleksander Popel, Ph.D., a professor of biomedical engineering at Hopkins. "Now, using a whole-genome, computer-based approach, we have identified more than 100 new ones, all of which can be further researched for their ability to fight the more than 30 known diseases affected by excessive blood vessel growth."
To identify short protein fragments - peptides - that can block blood vessel growth, the team started by looking at 40 known peptides that have been studied and characterized by other experts in the field to stop blood vessel growth in animal models of disease. Working under the assumption that the antivessel activity of these peptides can be attributed to similar features that are shared by a number of proteins, like the sequence of the peptide building blocks, the team first categorized the 40 known peptides by where they are located and what they look like.
Having defined nine families, the researchers then used computer programs and compared the peptide families to all of the proteins encoded by the genome. They found more than 120 peptides contained in 82 different proteins, many of which were not previously known to have any activity on blood vessel development.
"Computational methods only identify potential candidates," says Popel. "We next had to do the experiments on live cells to see if they had any real activity. Of the 82 proteins we identified, most were not previously known to have any antiangiogenic activity."
To test the activity of these candidate peptides, the researchers applied them to blood vessel cells growing in the lab and examined whether they had any effect on the growth, survival and movement of these cells. To test growth and survival, they added different amounts of peptide to dishes containing roughly 2,000 cells and after three days, counted how many cells were still alive.
To test cell movement, they placed cells in double-chambered dishes and treated the cells with a growth factor known to encourage cells to move. To some of the dishes they added the test peptides. After 20 hours, they measured the number of cells that had crawled from one chamber to the other. They then identified the protein receptors that the peptides bind to and were able to show in some cases that combinations of more than one peptide were better able to stop the cells than using single peptides.
"Basic, computational studies like this are critical to understanding normal blood vessel growth," says Popel. "A better understanding of normal growth gives us a better idea of what happens in disease."
The next step, Popel says, is to test these peptides in animal models of human disease and to identify the diseases most appropriately treated by these newly identified peptide inhibitors.
This study was funded by the National Heart, Lung and Blood Institute and the National Cancer Institute.
Authors on the paper are Emmanouil Karagiannis and Popel, both of Johns Hopkins.
On the Web:
bme.jhu/people/primary.php?id=393
jhu/apopel/
pnas/
Source: Audrey Huang
Johns Hopkins Medical Institutions
Reporting online last week in the Proceedings of the National Academy of Sciences, the researchers say the findings could lead to developing treatments to fight diseases that depend on the growth of new blood vessels, including cancer, macular degeneration and rheumatoid arthritis.
"Before, there were only 40 known antiangiogenesis peptides," says Aleksander Popel, Ph.D., a professor of biomedical engineering at Hopkins. "Now, using a whole-genome, computer-based approach, we have identified more than 100 new ones, all of which can be further researched for their ability to fight the more than 30 known diseases affected by excessive blood vessel growth."
To identify short protein fragments - peptides - that can block blood vessel growth, the team started by looking at 40 known peptides that have been studied and characterized by other experts in the field to stop blood vessel growth in animal models of disease. Working under the assumption that the antivessel activity of these peptides can be attributed to similar features that are shared by a number of proteins, like the sequence of the peptide building blocks, the team first categorized the 40 known peptides by where they are located and what they look like.
Having defined nine families, the researchers then used computer programs and compared the peptide families to all of the proteins encoded by the genome. They found more than 120 peptides contained in 82 different proteins, many of which were not previously known to have any activity on blood vessel development.
"Computational methods only identify potential candidates," says Popel. "We next had to do the experiments on live cells to see if they had any real activity. Of the 82 proteins we identified, most were not previously known to have any antiangiogenic activity."
To test the activity of these candidate peptides, the researchers applied them to blood vessel cells growing in the lab and examined whether they had any effect on the growth, survival and movement of these cells. To test growth and survival, they added different amounts of peptide to dishes containing roughly 2,000 cells and after three days, counted how many cells were still alive.
To test cell movement, they placed cells in double-chambered dishes and treated the cells with a growth factor known to encourage cells to move. To some of the dishes they added the test peptides. After 20 hours, they measured the number of cells that had crawled from one chamber to the other. They then identified the protein receptors that the peptides bind to and were able to show in some cases that combinations of more than one peptide were better able to stop the cells than using single peptides.
"Basic, computational studies like this are critical to understanding normal blood vessel growth," says Popel. "A better understanding of normal growth gives us a better idea of what happens in disease."
The next step, Popel says, is to test these peptides in animal models of human disease and to identify the diseases most appropriately treated by these newly identified peptide inhibitors.
This study was funded by the National Heart, Lung and Blood Institute and the National Cancer Institute.
Authors on the paper are Emmanouil Karagiannis and Popel, both of Johns Hopkins.
On the Web:
bme.jhu/people/primary.php?id=393
jhu/apopel/
pnas/
Source: Audrey Huang
Johns Hopkins Medical Institutions
Moving Is The Best Medicine To Fight Arthritis Pain
The burden of arthritis is greater for African Americans and Hispanics, despite lower prevalence among these groups according to a Centers for Disease Control and Prevention (CDC) report published in the May issue of Preventing Chronic Disease. According to the Arthritis Foundation, these findings suggest a critical need to expand the reach of effective strategies aimed at arthritis prevention and management, particularly among groups bearing a disproportionate burden.
The report finds that the prevalence of activity limitation, work limitation and severe joint pain are significantly higher among African Americans and Hispanics. These two groups are nearly twice as likely as whites to have severe joint pain and work limitations and 1.3 times as likely to have activity limitations.
"Arthritis is a debilitating disease that profoundly impacts the lives of millions of Americans on a daily basis," said Dr. Patience White, vice president of public health for the Arthritis Foundation. "The effects of the 46 million Americans with arthritis on the economy are enormous; the direct and indirect medical costs of this disease are estimated to be $128 billion each year." With the aging of the baby boomer population, the prevalence of arthritis is expected to rise significantly from 46 million Americans to 67 million Americans by 2030, adds White.
Fortunately, there are simple steps everyone can take to prevent and decrease the pain and disability of arthritis. Small amounts of weight loss and physical activity can make a big difference. For example, for every one pound of weight loss, there is a four-pound reduction in the load exerted on each knee. In addition, safe and effective self-management education programs are available. People living with arthritis can benefit from participating in one of the Arthritis Foundation's exercise or self-management programs, such as the Arthritis Foundation Walk With Ease Program, Arthritis Foundation Aquatic Program, Arthritis Foundation Exercise Program, and Arthritis Foundation Self-Help Program.
Taking Action
Moving is the best medicine for arthritis and in recognition of Arthritis Awareness Month in May, the Arthritis Foundation is encouraging people with arthritis and the many more at risk to make physical activity part of their daily routine. To get started, go to fightarthritispain to find out your risk for osteoarthritis, the most common form of the disease, and learn how to manage your arthritis. Then, celebrate your commitment to move at an Arthritis Walk event. Visit letsmovetogether for more information about Arthritis Walk events taking place in your community and for a movement tracker to set goals and stay on track.
Source:
Carol Galbreath
Arthritis Foundation
The report finds that the prevalence of activity limitation, work limitation and severe joint pain are significantly higher among African Americans and Hispanics. These two groups are nearly twice as likely as whites to have severe joint pain and work limitations and 1.3 times as likely to have activity limitations.
"Arthritis is a debilitating disease that profoundly impacts the lives of millions of Americans on a daily basis," said Dr. Patience White, vice president of public health for the Arthritis Foundation. "The effects of the 46 million Americans with arthritis on the economy are enormous; the direct and indirect medical costs of this disease are estimated to be $128 billion each year." With the aging of the baby boomer population, the prevalence of arthritis is expected to rise significantly from 46 million Americans to 67 million Americans by 2030, adds White.
Fortunately, there are simple steps everyone can take to prevent and decrease the pain and disability of arthritis. Small amounts of weight loss and physical activity can make a big difference. For example, for every one pound of weight loss, there is a four-pound reduction in the load exerted on each knee. In addition, safe and effective self-management education programs are available. People living with arthritis can benefit from participating in one of the Arthritis Foundation's exercise or self-management programs, such as the Arthritis Foundation Walk With Ease Program, Arthritis Foundation Aquatic Program, Arthritis Foundation Exercise Program, and Arthritis Foundation Self-Help Program.
Taking Action
Moving is the best medicine for arthritis and in recognition of Arthritis Awareness Month in May, the Arthritis Foundation is encouraging people with arthritis and the many more at risk to make physical activity part of their daily routine. To get started, go to fightarthritispain to find out your risk for osteoarthritis, the most common form of the disease, and learn how to manage your arthritis. Then, celebrate your commitment to move at an Arthritis Walk event. Visit letsmovetogether for more information about Arthritis Walk events taking place in your community and for a movement tracker to set goals and stay on track.
Source:
Carol Galbreath
Arthritis Foundation
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