1. Obesity and Knee Osteoarthritis Significantly Cut Quality and Duration of Life
With obesity and life expectancy on the rise in the United States, knee osteoarthritis has become an increasingly prevalent problem. Researchers used a comprehensive computer model to assess the effect of obesity and knee osteoarthritis on remaining duration and quality of life among persons aged 50 to 84 years. Additionally, the researchers sought to determine the health benefits of reducing obesity prevalence in the United States to the level it was 10 years ago. According to the researchers' model, 40 percent of the 86 million Americans in the 50 to 84 age range have osteoarthritis, are obese, or both. Obesity reduces duration and quality of life by 12 percent and osteoarthritis by about 12 percent, suggesting that measures need to be taken to prevent and treat these conditions. The researchers found that black and Hispanic women had disproportionately high losses due to obesity and knee osteoarthritis, thus underscoring the need for prevention and treatment strategies specifically tailored to patient gender and race. The model suggested that reversing obesity prevalence to levels seen 10 years ago would avert hundreds of thousands of cases of knee replacements in addition to other diseases such as heart disease and diabetes and would increase life expectancy.
2. Patient Race, Other Personal Characteristics Determine Intensity of Care at End of Life
There is great variability in the intensity and cost of care near the end-of-life, but the characteristics that explain this variability are not well understood. Researchers studied Medicare records for 2,394 patients aged 65 and older to determine how regional and patient-level characteristics influence medical expenditures at end of life. The researchers found that while regional differences (number of hospital beds per capita, local or institutional patterns of care, physician practice patterns, etc.) in care intensity exist, a larger proportion of overall care variation is driven by differences in patient characteristics. Decline in functional status, minority race and ethnicity, certain chronic conditions, and the lack of nearby family support were associated with higher expenditures, accounting for approximately 10 percent of the variability in end-of-life care. According to the author of a corresponding editorial, ineffective communication may lead to some patients receiving more intensive care than they would choose if adequately informed about the benefits and harms associated with intense end-of-life care.
3. New Guideline from American College of Physicians: Use of Intensive Insulin Therapy for the Management of Glycemic Control in Hospitalized Patients
Recommendations are departure from current practice
Poorly controlled hyperglycemia is associated with increased illness, death, and worsening health outcomes in hospitalized patients. While most doctors make efforts to prevent and control hyperglycemia in hospital settings, the use of intensive insulin therapy and optimal blood glucose range to target in hospitalized patients has been uncertain. The Clinical Guidelines Committee of the American College of Physicians (ACP) analyzed published evidence to determine the appropriate use of intensive insulin therapy for the management glucose levels in hospitalized patients. Based on their review, ACP recommends that physicians not use intensive insulin therapy to strictly control blood glucose in non-surgical intensive care unit (SICU) or non-medical intensive care unit (MICU) patients with or without diabetes. ACP also recommends not using intensive insulin therapy to normalize blood glucose in SICU or MICU patients with or without diabetes. If insulin therapy is used in SICU or MICU patients, physicians should target a blood glucose level of 140 to 200 mg to avoid hypoglycemia.
Early Releases:
4. Cardiac Resynchronization Therapy Safe and Effective for Patients with Less Symptomatic Heart Failure
Cardiac resynchronization therapy (CRT) has been shown to reduce morbidity and mortality in patients with advanced heart failure (HF) symptoms. In an update to their previous review, researchers studied data from 25 published randomized controlled trials with a total of 9,082 patients to determine if CRT also benefits less symptomatic heart patients. All-cause mortality was the primary end point for the study, but the researchers also looked at HF hospitalizations, quality of life, and functional outcomes. They found that CRT is beneficial for patients with reduced left ventricular ejection fraction (the percentage of blood pumped during each contraction) symptoms and prolonged QRS (time between heart beats), regardless of NYHA class (measurement of severity of HF symptoms). They concluded that CRT improves left ventricular ejection fraction and reduces all-cause mortality and HF hospitalizations in patients with less severe disease, supporting the expansion of indications for CRT.
5. Atazanavir/Ritonavir Combo has Similar Virologic Efficacy to Efavirenz When Used as Part of a Three-Drug Regimen for Initial Treatment of HIV-1
Current treatment guidelines for initial treatment of HIV-1 recommend two nucleoside reverse transcriptase inhibitors (NRTIs) with either a non-NRTI (NNRTI), ritonavir-boosted protease inhibitor (PI) or integrase inhibitor. Limited data compare atazanavir/ritonavir and efavirenz, which are once-daily options for inclusion in initial therapy of human immunodeficiency virus type 1 (HIV-1). Researchers randomly assigned 1,857 patients over the age of 16 to take either atazanavir/ritonavir or efavirenze with either of the following combinations abacavir/lamivudine or tenofovir DF/emtricitabine HR. The researchers' analysis showed that atazanavir/ritonavir and efavirenz-based regimens had -similar virologic efficacy. The safety and tolerability endpoints were lower among those assigned to atazanavir/ritonavir than efavirenz when combined with abacavir/lamivudine, but were the same when combined with tenofovir DF/emtricitabine. The study authors suggest that these results be taken into consideration when clinicians select initial treatment regimens for patients with HIV-1 infection.
Source:
Angela Collom
American College of Physicians
вторник, 21 июня 2011 г.
понедельник, 20 июня 2011 г.
Low Vitamin D Levels Associated With Chronic Pain In Women
Low vitamin D levels may contribute to chronic pain among women, suggests research published ahead of print in the Annals of the Rheumatic Diseases.
The findings are based on the blood analyses and pain scores of almost 7000 45 year old men and women from across England, Scotland and Wales, all of whom were born during one week in March 1958.
Smokers, non-drinkers, the overweight and the underweight all reported higher rates of chronic pain.
The extent of chronic widespread pain did not vary among men according to vitamin D levels. However, this was not the case for women.
Women with vitamin D levels between 75 and 99 mmol/litre had the lowest rates of this type of pain, at just over 8%.
Women with levels of less than 25 mmol/litre had the highest rates, at 14.4%.
There appeared to be a J shaped curve, with the prevalence of widespread pain at 10% or higher among those with vitamin D levels above 99 mmol/litre.
The findings were not explained by gender differences in lifestyle or social factors, such as levels of physical activity and time spent outdoors, say the authors.
And at the age of 45, few of the women would have entered the menopause, a period during which bone mineral density falls as oestrogen levels dwindle.
But by way of possible explanations, the authors point to osteomalacia, a disease of extreme vitamin D deficiency, which is associated with isolated or generalised bone pain. The hormonally active form of vitamin D is also involved in the regulation of immune system responses.
Around one in 10 of the population suffers from chronic widespread pain at any one time, say the authors.
The causes are not fully understood, but social and psychological factors are known to affect the sensation and reporting of pain.
Vitamin D and chronic widespread pain in a white middle aged British population: evidence from a cross sectional population study
Online First AnnRheum Dis2008 doi: 10.1136/ard/2008.090456
Click here to view article online
Annals of The Rheumatic Diseases
Annals of The Rheumatic Diseases (ARD) is an international peer review journal committed to promoting the highest standards of scientific exchange and education. It covers all aspects of rheumatology, which includes the spectrum of musculoskeletal conditions, arthritic disease, and connective tissue disorders. ARD publishes basic, clinical, and translational scientific research. Concise scientific communication is encouraged and peer reviewed proceedings of international meetings are featured. Educational papers include state of the art reviews, "how to" articles and educational cases that focus on problems faced in clinical practice. The journal was first published in 1939 and has an authorative global Editorial Board and a growing international readership.
What is pain?
For more information on what pain is and possible treatments, please see:
What is Pain? What Causes Pain?
The findings are based on the blood analyses and pain scores of almost 7000 45 year old men and women from across England, Scotland and Wales, all of whom were born during one week in March 1958.
Smokers, non-drinkers, the overweight and the underweight all reported higher rates of chronic pain.
The extent of chronic widespread pain did not vary among men according to vitamin D levels. However, this was not the case for women.
Women with vitamin D levels between 75 and 99 mmol/litre had the lowest rates of this type of pain, at just over 8%.
Women with levels of less than 25 mmol/litre had the highest rates, at 14.4%.
There appeared to be a J shaped curve, with the prevalence of widespread pain at 10% or higher among those with vitamin D levels above 99 mmol/litre.
The findings were not explained by gender differences in lifestyle or social factors, such as levels of physical activity and time spent outdoors, say the authors.
And at the age of 45, few of the women would have entered the menopause, a period during which bone mineral density falls as oestrogen levels dwindle.
But by way of possible explanations, the authors point to osteomalacia, a disease of extreme vitamin D deficiency, which is associated with isolated or generalised bone pain. The hormonally active form of vitamin D is also involved in the regulation of immune system responses.
Around one in 10 of the population suffers from chronic widespread pain at any one time, say the authors.
The causes are not fully understood, but social and psychological factors are known to affect the sensation and reporting of pain.
Vitamin D and chronic widespread pain in a white middle aged British population: evidence from a cross sectional population study
Online First AnnRheum Dis2008 doi: 10.1136/ard/2008.090456
Click here to view article online
Annals of The Rheumatic Diseases
Annals of The Rheumatic Diseases (ARD) is an international peer review journal committed to promoting the highest standards of scientific exchange and education. It covers all aspects of rheumatology, which includes the spectrum of musculoskeletal conditions, arthritic disease, and connective tissue disorders. ARD publishes basic, clinical, and translational scientific research. Concise scientific communication is encouraged and peer reviewed proceedings of international meetings are featured. Educational papers include state of the art reviews, "how to" articles and educational cases that focus on problems faced in clinical practice. The journal was first published in 1939 and has an authorative global Editorial Board and a growing international readership.
What is pain?
For more information on what pain is and possible treatments, please see:
What is Pain? What Causes Pain?
воскресенье, 19 июня 2011 г.
Launch of ENBREL for Rheumatoid Arthritis, Japan
Wyeth KK and Takeda Pharmaceutical Company
Limited ("Takeda") announced today that ENBREL (etanercept) will be launched in Japan for
the treatment of rheumatoid arthritis (RA) on March 30 under the co-promotion
agreement of both parties. The launch follows regulatory approval in January and
National Health Insurance (NHI) listing on March 18.
ENBREL is the only fully human, anti-TNF receptor approved to reduce the signs
and symptoms of RA in patients who had an inadequate response to existing
disease-modifying antirheumatic medicines. The biological product can be used alone
as a monotherapy and is administered twice weekly as a subcutaneous injection.
Initially the product will be made available to medical institutions participating
in an all-patient surveillance program.
"The results of the clinical studies with ENBREL in Japan were very
encouraging, with some patients responding as early as two weeks after beginning
treatment and reaching maximum relief within the first two months," said the primary
investigator Prof. Nobuyuki Miyasaka, M.D., Department of Bioregulatory Medicine and
Rheumatology of Tokyo Medical and Dental University.
"The launch of this therapeutic breakthrough brings physicians and patients a
new option in the treatment of rheumatoid arthritis. We look forward to providing
ENBREL to patients who have gone for so long with few effective options to
significantly reduce the painful symptoms of their disease," says Dr. Michio Suzukawa,
Corporate Officer, Director, Medical Affairs Division of Wyeth K. K.
"We are pleased to introduce ENBREL, which already has been widely used for RA
patients worldwide, with Wyeth K.K. in Japan," says Mr. Makoto Yamaoka, Managing
Director, General Manager of Pharmaceutical Marketing Division of Takeda.
About Rheumatoid Arthritis
Rheumatoid arthritis is a systemic, chronic and potentially disabling disorder that
affects about 700,000 people in Japan. The serious rheumatic disease causes the body's
immune system to attack the lining of the joints, resulting in pain and swelling and may
lead to fatigue, disability, deformity, organ damage, or premature death if not managed
effectively. In RA, the immune system attacks the body?fs own healthy cells, mistaking
them for cells that do not belong. This causes inflammation in the lining and connective
tissues of the joints. Generally, in Japan the disease affects about four times as many
women as men*. RA can develop at all ages including childhood; in most cases it develops
between the ages of 25 and 50.
* The Japan Medical Association
About ENBREL
In Japan ENBREL was approved for the treatment of rheumatoid arthritis in patients who
had an inadequate response to existing therapies. ENBREL acts by binding TNF, one of
the dominant inflammatory cytokines or regulatory proteins that play an important role
in both normal immune function and the cascade of reactions causing the inflammatory
process of rheumatoid arthritis. The binding of ENBREL to TNF renders the bound TNF
biologically inactive, resulting in significant reduction in inflammatory activity.
Additionally, ENBREL binds to lymphotoxin (LT)-alpha, another cytokine involved in the
inflammatory process of RA.
Globally physicians have become familiar with the benefits and proven long-term profile
of ENBREL. As of today, the product has been approved in more than 70 countries around
the world, and has been used to treat more than 280,000 patients worldwide across various
indications.
Important Treatment Considerations
Since the product was first introduced globally, serious infections, some involving
death, have been reported in patients using ENBREL. The product should be used with
caution in patients prone to infection. There have been reports of serious nervous-system
disorders such as multiple sclerosis, or inflammation of the nerves of the eyes. There
also have been rare reports of serious blood disorders, some involving death. It is
unclear if ENBREL has caused these nervous-system or blood disorders. The most frequent
adverse events in clinical trials in patients with rheumatoid arthritis (RA) were
infections, injection-site reactions, headaches, and respiratory disorders. In medical
studies of all TNF-inhibitors, a higher rate of lymphoma (a type of cancer) was seen
compared to the general population, however, the risk of lymphoma may be up to several
fold higher in RA patients. The role of TNF-inhibitors in the development of lymphoma
is unknown. The incidence of other cancers has not increased with extended exposure to
ENBREL and is similar to the expected rate.
About Wyeth K.K.
Wyeth K.K. is engaged in a full range of pharmaceutical business activities including
developing, importing, manufacturing and marketing pharmaceutical products with the
aim of becoming a leading company in the pharmaceutical industry in Japan. Our corporate
vision is Leading the way to a healthier world. We strive to achieve this vision by
bringing to the world pharmaceutical and health-care products that improve peoples'
lives and deliver outstanding value to our customers. Wyeth K.K. (WKK), previously known
as Wyeth Lederle Japan, Ltd., was established in 1998 with the combination of Lederle
Japan, Ltd. and Wyeth (Japan) Corporation, both of which were founded in the mid-1950's.
WKK's major shareholders are Wyeth with 60 percent of the equity and Takeda Pharmaceutical
Company Limited with 40 percent. Headquartered in Tokyo, WKK has more than 1,200 employees
with manufacturing facilities located in the city of Shiki, Saitama Prefecture and business
offices located in seven major cities throughout Japan. See details, at wyeth.jp.
About Takeda
Takeda, in its management plan, sets a course by which the company will become an
" R&D-driven world-class pharmaceutical company" . Takeda will exert its best efforts to
enhance its R&D pipeline in selected core therapeutic classes such as "lifestyle-related
diseases", "cancer and urological diseases and gynecological disorders", "central nervous
system disorders, and bone and joint diseases", and "life-cycle management of drugs for
digestive system disorders".
Takeda is reinforcing its in-house R&D, promoting life cycle management, and actively
introducing new products and form alliances in order to realize its management mission of
?estriving toward better health for individuals and progress in medicine by developing
superior pharmaceutical products'. See details at takeda.co.jp.
View drug information on Enbrel.
Limited ("Takeda") announced today that ENBREL (etanercept) will be launched in Japan for
the treatment of rheumatoid arthritis (RA) on March 30 under the co-promotion
agreement of both parties. The launch follows regulatory approval in January and
National Health Insurance (NHI) listing on March 18.
ENBREL is the only fully human, anti-TNF receptor approved to reduce the signs
and symptoms of RA in patients who had an inadequate response to existing
disease-modifying antirheumatic medicines. The biological product can be used alone
as a monotherapy and is administered twice weekly as a subcutaneous injection.
Initially the product will be made available to medical institutions participating
in an all-patient surveillance program.
"The results of the clinical studies with ENBREL in Japan were very
encouraging, with some patients responding as early as two weeks after beginning
treatment and reaching maximum relief within the first two months," said the primary
investigator Prof. Nobuyuki Miyasaka, M.D., Department of Bioregulatory Medicine and
Rheumatology of Tokyo Medical and Dental University.
"The launch of this therapeutic breakthrough brings physicians and patients a
new option in the treatment of rheumatoid arthritis. We look forward to providing
ENBREL to patients who have gone for so long with few effective options to
significantly reduce the painful symptoms of their disease," says Dr. Michio Suzukawa,
Corporate Officer, Director, Medical Affairs Division of Wyeth K. K.
"We are pleased to introduce ENBREL, which already has been widely used for RA
patients worldwide, with Wyeth K.K. in Japan," says Mr. Makoto Yamaoka, Managing
Director, General Manager of Pharmaceutical Marketing Division of Takeda.
About Rheumatoid Arthritis
Rheumatoid arthritis is a systemic, chronic and potentially disabling disorder that
affects about 700,000 people in Japan. The serious rheumatic disease causes the body's
immune system to attack the lining of the joints, resulting in pain and swelling and may
lead to fatigue, disability, deformity, organ damage, or premature death if not managed
effectively. In RA, the immune system attacks the body?fs own healthy cells, mistaking
them for cells that do not belong. This causes inflammation in the lining and connective
tissues of the joints. Generally, in Japan the disease affects about four times as many
women as men*. RA can develop at all ages including childhood; in most cases it develops
between the ages of 25 and 50.
* The Japan Medical Association
About ENBREL
In Japan ENBREL was approved for the treatment of rheumatoid arthritis in patients who
had an inadequate response to existing therapies. ENBREL acts by binding TNF, one of
the dominant inflammatory cytokines or regulatory proteins that play an important role
in both normal immune function and the cascade of reactions causing the inflammatory
process of rheumatoid arthritis. The binding of ENBREL to TNF renders the bound TNF
biologically inactive, resulting in significant reduction in inflammatory activity.
Additionally, ENBREL binds to lymphotoxin (LT)-alpha, another cytokine involved in the
inflammatory process of RA.
Globally physicians have become familiar with the benefits and proven long-term profile
of ENBREL. As of today, the product has been approved in more than 70 countries around
the world, and has been used to treat more than 280,000 patients worldwide across various
indications.
Important Treatment Considerations
Since the product was first introduced globally, serious infections, some involving
death, have been reported in patients using ENBREL. The product should be used with
caution in patients prone to infection. There have been reports of serious nervous-system
disorders such as multiple sclerosis, or inflammation of the nerves of the eyes. There
also have been rare reports of serious blood disorders, some involving death. It is
unclear if ENBREL has caused these nervous-system or blood disorders. The most frequent
adverse events in clinical trials in patients with rheumatoid arthritis (RA) were
infections, injection-site reactions, headaches, and respiratory disorders. In medical
studies of all TNF-inhibitors, a higher rate of lymphoma (a type of cancer) was seen
compared to the general population, however, the risk of lymphoma may be up to several
fold higher in RA patients. The role of TNF-inhibitors in the development of lymphoma
is unknown. The incidence of other cancers has not increased with extended exposure to
ENBREL and is similar to the expected rate.
About Wyeth K.K.
Wyeth K.K. is engaged in a full range of pharmaceutical business activities including
developing, importing, manufacturing and marketing pharmaceutical products with the
aim of becoming a leading company in the pharmaceutical industry in Japan. Our corporate
vision is Leading the way to a healthier world. We strive to achieve this vision by
bringing to the world pharmaceutical and health-care products that improve peoples'
lives and deliver outstanding value to our customers. Wyeth K.K. (WKK), previously known
as Wyeth Lederle Japan, Ltd., was established in 1998 with the combination of Lederle
Japan, Ltd. and Wyeth (Japan) Corporation, both of which were founded in the mid-1950's.
WKK's major shareholders are Wyeth with 60 percent of the equity and Takeda Pharmaceutical
Company Limited with 40 percent. Headquartered in Tokyo, WKK has more than 1,200 employees
with manufacturing facilities located in the city of Shiki, Saitama Prefecture and business
offices located in seven major cities throughout Japan. See details, at wyeth.jp.
About Takeda
Takeda, in its management plan, sets a course by which the company will become an
" R&D-driven world-class pharmaceutical company" . Takeda will exert its best efforts to
enhance its R&D pipeline in selected core therapeutic classes such as "lifestyle-related
diseases", "cancer and urological diseases and gynecological disorders", "central nervous
system disorders, and bone and joint diseases", and "life-cycle management of drugs for
digestive system disorders".
Takeda is reinforcing its in-house R&D, promoting life cycle management, and actively
introducing new products and form alliances in order to realize its management mission of
?estriving toward better health for individuals and progress in medicine by developing
superior pharmaceutical products'. See details at takeda.co.jp.
View drug information on Enbrel.
суббота, 18 июня 2011 г.
Medarex Announces Allowance Of Investigational New Drug Applications For Wholly Owned Fully Human Anti-CD19 Antibody, MDX-1342
Medarex, Inc.
(Nasdaq: MEDX) announced the allowance of two separate
investigational new drug applications (IND) filed with the U.S. Food & Drug
Administration (FDA) for MDX-1342, one for the treatment of chronic
lymphocytic leukemia (CLL) and the other for rheumatoid arthritis. MDX-1342
is a fully human antibody that targets CD19, a molecule specifically
expressed on normal B-cells and malignant B-cells in diseases such as CLL,
acute lymphoblastic leukemia, follicular non-Hodgkins lymphoma, diffuse
large B-cell lymphoma and mantle cell lymphoma.
The IND for the treatment of CLL is for an open-label, multi-dose,
dose-escalation Phase I clinical trial for cancer that is expected to
enroll up to 52 patients with relapsed or refractory CLL. This trial is
designed to establish and evaluate the safety, tolerability and maximum
tolerated dose, as well as preliminary pharmacodynamics and efficacy of
MDX-1342.
The IND for the treatment of rheumatoid arthritis is for a randomized,
single-dose, dose-escalation, placebo-controlled Phase I clinical trial
that is expected to enroll up to 90 patients with rheumatoid arthritis.
This trial is designed to evaluate the safety and tolerability profile of
MDX-1342 and to determine the dose range for B-cell depletion.
"We are pleased with the advancement of a new product candidate from
Medarex's proprietary pipeline into clinical trials," said Howard H. Pien,
President and CEO of Medarex. "We look forward to the continued development
of MDX-1342, which could provide new treatment options for a number of
serious conditions."
About CD19 and MDX-1342
CD19 is a B-cell specific membrane protein that is broadly expressed
during B-cell development, from the pro-B-cell to the early plasma cell
stage.
Clinical studies have demonstrated that depleting monoclonal antibodies
directed against CD20, another B-cell specific membrane protein that has a
more restricted expression pattern than CD19 during B-cell development, are
effective in treating rheumatoid arthritis and various B-cell malignancies,
and show promise in treating other inflammatory diseases such as systemic
lupus erythematosis and multiple sclerosis.
MDX-1342 is a fully human antibody that binds selectively to CD19
expressed on B-cells (without targeting stem cells or fully differentiated
plasma cells, which lack CD19 expression) and induces the depletion and
elimination of CD19-positive B-cells.
About Chronic Lymphocytic Leukemia
Chronic Lymphocytic Leukemia (CLL) is a cancer that affects B-cell
lymphocytes, an important component of the immune system that helps the
body fight infection or cancer. The American Cancer Society estimates that
in 2007, approximately 15,340 new cases of chronic lymphocytic leukemia
will occur in the United States, and approximately 4,500 people will die of
the disease in 2007.
About Rheumatoid Arthritis
According to the American College of Rheumatology, more than two
million Americans suffer from rheumatoid arthritis (RA), a chronic
autoimmune disease that develops when certain cells of the immune system
inappropriately attack healthy joint tissue, thereby causing swelling,
inflammation and damage of joints, as well as systemic inflammation and
damage of other tissues.
About Medarex
Medarex is a biopharmaceutical company focused on the discovery,
development and potential commercialization of fully human antibody-based
therapeutics to treat life-threatening and debilitating diseases, including
cancer, inflammation, autoimmune disorders and infectious diseases. Medarex
applies its UltiMAb(R) technology and product development and clinical
manufacturing experience to generate, support and potentially commercialize
a broad range of fully human antibody product candidates for itself and its
partners. More than 30 of these therapeutic product candidates derived from
Medarex technology are in human clinical testing or have had INDs submitted
for such trials, with seven of the most advanced product candidates
currently in Phase III clinical trials. Medarex is committed to building
value by developing a diverse pipeline of antibody products to address the
world's unmet healthcare needs. For more information about Medarex, visit
its website at medarex.
Statement on Cautionary Factors
Except for the historical information presented herein, matters
discussed herein may constitute forward-looking statements that are subject
to certain risks and uncertainties that could cause actual results to
differ materially from any future results, performance or achievements
expressed or implied by such statements. Statements that are not historical
facts, including statements preceded by, followed by, or that include the
words "expect"; "potential"; "could"; "may"; or similar statements are
forward-looking statements. Medarex disclaims, however, any intent or
obligation to update these forward-looking statements. Risks and
uncertainties include risks associated with product discovery and
development, uncertainties related to the outcome of clinical trials,
slower than expected rates of patient recruitment, unforeseen safety issues
resulting from the administration of MDX-1342 in patients, uncertainties
related to product manufacturing as well as risks detailed from time to
time in Medarex's public disclosure filings with the U.S. Securities and
Exchange Commission (SEC), including its Annual Report on Form 10-K for the
fiscal year ended December 31, 2006 and its quarterly reports on Form 10-Q.
There can be no assurance that such development efforts will succeed or
that other developed products will receive required regulatory clearance or
that, even if such regulatory clearance were received, such products would
ultimately achieve commercial success. Copies of Medarex's public
disclosure filings are available from its investor relations department.
Medarex(R), the Medarex logo and UltiMAb(R) are registered trademarks
of Medarex, Inc. All rights are reserved.
Medarex, Inc.
medarex
(Nasdaq: MEDX) announced the allowance of two separate
investigational new drug applications (IND) filed with the U.S. Food & Drug
Administration (FDA) for MDX-1342, one for the treatment of chronic
lymphocytic leukemia (CLL) and the other for rheumatoid arthritis. MDX-1342
is a fully human antibody that targets CD19, a molecule specifically
expressed on normal B-cells and malignant B-cells in diseases such as CLL,
acute lymphoblastic leukemia, follicular non-Hodgkins lymphoma, diffuse
large B-cell lymphoma and mantle cell lymphoma.
The IND for the treatment of CLL is for an open-label, multi-dose,
dose-escalation Phase I clinical trial for cancer that is expected to
enroll up to 52 patients with relapsed or refractory CLL. This trial is
designed to establish and evaluate the safety, tolerability and maximum
tolerated dose, as well as preliminary pharmacodynamics and efficacy of
MDX-1342.
The IND for the treatment of rheumatoid arthritis is for a randomized,
single-dose, dose-escalation, placebo-controlled Phase I clinical trial
that is expected to enroll up to 90 patients with rheumatoid arthritis.
This trial is designed to evaluate the safety and tolerability profile of
MDX-1342 and to determine the dose range for B-cell depletion.
"We are pleased with the advancement of a new product candidate from
Medarex's proprietary pipeline into clinical trials," said Howard H. Pien,
President and CEO of Medarex. "We look forward to the continued development
of MDX-1342, which could provide new treatment options for a number of
serious conditions."
About CD19 and MDX-1342
CD19 is a B-cell specific membrane protein that is broadly expressed
during B-cell development, from the pro-B-cell to the early plasma cell
stage.
Clinical studies have demonstrated that depleting monoclonal antibodies
directed against CD20, another B-cell specific membrane protein that has a
more restricted expression pattern than CD19 during B-cell development, are
effective in treating rheumatoid arthritis and various B-cell malignancies,
and show promise in treating other inflammatory diseases such as systemic
lupus erythematosis and multiple sclerosis.
MDX-1342 is a fully human antibody that binds selectively to CD19
expressed on B-cells (without targeting stem cells or fully differentiated
plasma cells, which lack CD19 expression) and induces the depletion and
elimination of CD19-positive B-cells.
About Chronic Lymphocytic Leukemia
Chronic Lymphocytic Leukemia (CLL) is a cancer that affects B-cell
lymphocytes, an important component of the immune system that helps the
body fight infection or cancer. The American Cancer Society estimates that
in 2007, approximately 15,340 new cases of chronic lymphocytic leukemia
will occur in the United States, and approximately 4,500 people will die of
the disease in 2007.
About Rheumatoid Arthritis
According to the American College of Rheumatology, more than two
million Americans suffer from rheumatoid arthritis (RA), a chronic
autoimmune disease that develops when certain cells of the immune system
inappropriately attack healthy joint tissue, thereby causing swelling,
inflammation and damage of joints, as well as systemic inflammation and
damage of other tissues.
About Medarex
Medarex is a biopharmaceutical company focused on the discovery,
development and potential commercialization of fully human antibody-based
therapeutics to treat life-threatening and debilitating diseases, including
cancer, inflammation, autoimmune disorders and infectious diseases. Medarex
applies its UltiMAb(R) technology and product development and clinical
manufacturing experience to generate, support and potentially commercialize
a broad range of fully human antibody product candidates for itself and its
partners. More than 30 of these therapeutic product candidates derived from
Medarex technology are in human clinical testing or have had INDs submitted
for such trials, with seven of the most advanced product candidates
currently in Phase III clinical trials. Medarex is committed to building
value by developing a diverse pipeline of antibody products to address the
world's unmet healthcare needs. For more information about Medarex, visit
its website at medarex.
Statement on Cautionary Factors
Except for the historical information presented herein, matters
discussed herein may constitute forward-looking statements that are subject
to certain risks and uncertainties that could cause actual results to
differ materially from any future results, performance or achievements
expressed or implied by such statements. Statements that are not historical
facts, including statements preceded by, followed by, or that include the
words "expect"; "potential"; "could"; "may"; or similar statements are
forward-looking statements. Medarex disclaims, however, any intent or
obligation to update these forward-looking statements. Risks and
uncertainties include risks associated with product discovery and
development, uncertainties related to the outcome of clinical trials,
slower than expected rates of patient recruitment, unforeseen safety issues
resulting from the administration of MDX-1342 in patients, uncertainties
related to product manufacturing as well as risks detailed from time to
time in Medarex's public disclosure filings with the U.S. Securities and
Exchange Commission (SEC), including its Annual Report on Form 10-K for the
fiscal year ended December 31, 2006 and its quarterly reports on Form 10-Q.
There can be no assurance that such development efforts will succeed or
that other developed products will receive required regulatory clearance or
that, even if such regulatory clearance were received, such products would
ultimately achieve commercial success. Copies of Medarex's public
disclosure filings are available from its investor relations department.
Medarex(R), the Medarex logo and UltiMAb(R) are registered trademarks
of Medarex, Inc. All rights are reserved.
Medarex, Inc.
medarex
пятница, 17 июня 2011 г.
Smoking, Low Levels Of Education And Glucose Tolerance Increase Risk Of Rheumatoid Arthritis
New data presented at EULAR 2007, the Annual European Congress of Rheumatology in Barcelona, Spain, sheds light on the role of environmental and genetic risk factors in the development of rheumatoid arthritis (RA). Two new studies by a team in Sweden have identified smoking, a low formal level of education and certain metabolic indicators as important risk factors in the development of RA. These findings represent a significant step towards better understanding of the risk factors for RA and may contribute to improved future prevention and treatment of this debilitating disease.
The first study showed that smoking (odds ratio 1.77; 95% confidence interval 1.13 to 2.78) and a low level of formal education, such as elementary school education only versus university degree status (odds ratio 2.46 confidence interval 1.20 to 5.02), may independently increase the risk of developing RA.
The second study similarly highlights the link between of smoking and RA but, contrary to previously noted relationships between RA with active inflammation and impaired glucose tolerance, observes better glucose tolerance as a predictor of RA. In the multivariate model, a lower glucose level at 120 minutes after an oral glucose tolerance test (odds ratio 1.19 per mmol/L; confidence interval 1.04 to 1.35) and smoking (odds ratio 1.64; confidence interval 1.08 to 2.48) were both found to be independent predictors of RA. Thus the authors suggest that factors such as diet and genetics influencing metabolism may play an important part in RA development.
Dr Ulf Bergstr?¶m from the Malm?¶ University Hospital, Sweden, lead investigator on both studies said, "The determinants for developing RA in any population are clearly complex and often unrelated. These studies help us to add more pieces to the giant jigsaw of risk factors for one of the most common autoimmune diseases, affecting approximately 1% of adults worldwide. We hope these findings will contribute to better understanding of future RA prevention and treatment. Whilst the glucose tolerance findings contrast with previous studies linking impaired tolerance to established RA, they suggest that other mechanisms may be important years before RA onset. Our results will pave the way for future debate and research to pinpoint its definitive causes."
The two studies involved people enrolled in the Malm?¶ Diet and Cancer Study (MDCS) (n=30,447) between 1991 and 1996 and a Preventive Medicine Program (PMP) (n=33,346) between 1974 and 1992. Investigators examined lifestyle factors using a self-administered questionnaire and glucose tolerance and lipids readings were taken by health professionals. Individuals who developed RA after participation in the health surveys were compared to controls without RA from the PMP and MDCS, matched for age, sex and year of screening.
Contact: EULAR Press Office
European League Against Rheumatism
The first study showed that smoking (odds ratio 1.77; 95% confidence interval 1.13 to 2.78) and a low level of formal education, such as elementary school education only versus university degree status (odds ratio 2.46 confidence interval 1.20 to 5.02), may independently increase the risk of developing RA.
The second study similarly highlights the link between of smoking and RA but, contrary to previously noted relationships between RA with active inflammation and impaired glucose tolerance, observes better glucose tolerance as a predictor of RA. In the multivariate model, a lower glucose level at 120 minutes after an oral glucose tolerance test (odds ratio 1.19 per mmol/L; confidence interval 1.04 to 1.35) and smoking (odds ratio 1.64; confidence interval 1.08 to 2.48) were both found to be independent predictors of RA. Thus the authors suggest that factors such as diet and genetics influencing metabolism may play an important part in RA development.
Dr Ulf Bergstr?¶m from the Malm?¶ University Hospital, Sweden, lead investigator on both studies said, "The determinants for developing RA in any population are clearly complex and often unrelated. These studies help us to add more pieces to the giant jigsaw of risk factors for one of the most common autoimmune diseases, affecting approximately 1% of adults worldwide. We hope these findings will contribute to better understanding of future RA prevention and treatment. Whilst the glucose tolerance findings contrast with previous studies linking impaired tolerance to established RA, they suggest that other mechanisms may be important years before RA onset. Our results will pave the way for future debate and research to pinpoint its definitive causes."
The two studies involved people enrolled in the Malm?¶ Diet and Cancer Study (MDCS) (n=30,447) between 1991 and 1996 and a Preventive Medicine Program (PMP) (n=33,346) between 1974 and 1992. Investigators examined lifestyle factors using a self-administered questionnaire and glucose tolerance and lipids readings were taken by health professionals. Individuals who developed RA after participation in the health surveys were compared to controls without RA from the PMP and MDCS, matched for age, sex and year of screening.
Contact: EULAR Press Office
European League Against Rheumatism
четверг, 16 июня 2011 г.
FDA Accepts REMICADE(R) Supplemental Biologics License Application For Inhibition Of Structural Damage For Patients With Psoriatic Arthritis
Centocor, Inc. announced today
that the US Food and Drug Administration (FDA) has accepted its filing of a
supplemental Biologics License Application (sBLA) for REMICADE(R)
(infliximab) for inhibiting the progression of structural damage and
improving physical function in patients with active psoriatic arthritis
(PsA). The filing is based on one-year data from the double-blind,
placebo-controlled trial IMPACT 2 and two-year data from the double-blind,
placebo-controlled trial IMPACT. PsA is a chronic, progressive and
potentially debilitating disease that causes joint inflammation and is
frequently associated with skin plaques of psoriasis.
"Findings from IMPACT 2 show that early intervention with REMICADE
therapy can significantly inhibit the progression of joint damage, which is
an important factor in the long-term prognosis of patients with psoriatic
arthritis," said Jerome A. Boscia, MD, Senior Vice President, Clinical
Research and Development, Centocor, Inc. "We are encouraged by these data
and are pleased that the FDA has accepted the file for review."
One-year radiographic analyses from IMPACT 2 showed that treatment with
REMICADE resulted in significantly greater inhibition of the progression of
structural damage, compared with placebo (as measured by the change from
baseline in van der Heijde-Sharp [vdH-S] score modified for PsA by adding
measurement for distal interphalangeal joints of the hands). In this method
a higher change in score indicates greater structural damage, while lower
change in score indicates less structural damage. At as early as 24 weeks
of treatment, REMICADE-treated patients experienced a mean change (+/-
standard deviation) in vdH-S score of -0.70 (+/- 2.53) from baseline,
compared with an average change of 0.82 (+/- 2.62) in the placebo group (P
< 0.001). At week 54, patients who received a full 54-week regimen of
REMICADE experienced a mean change of -0.94 (+/- 3.40) from baseline,
compared with an average change of 0.53 (+/- 2.60) in patients who crossed
over from placebo to REMICADE (P = 0.001) at week 16 or 24. Patients
randomized to REMICADE and placebo patients who crossed over to REMICADE
experienced a total improvement of -0.24 (+/- 2.45) and -0.29 (+/- 1.98),
respectively, from week 24 to 54, after all patients switched to treatment
with REMICADE.
REMICADE-treated patients demonstrated significant improvement in
physical function as measured by the Health Assessment Questionnaire (HAQ).
The HAQ assesses the difficulty a patient has accomplishing tasks in eight
functional areas (dressing, arising, eating, walking, hygiene, reaching,
gripping and other activities of daily living). As early as week 14,
patients in the REMICADE group experienced a median improvement of 43
percent, compared with zero percent in the placebo group (P < 0.001), and
results were maintained through one year. At week 54, there was a median 50
percent improvement in HAQ score from baseline in the group randomized to
REMICADE, and a 46 percent improvement in placebo patients who switched to
REMICADE. At week 54, 59 percent of REMICADE randomized patients and 53
percent of placebo patients who crossed over to REMICADE had improvement in
HAQ by greater than or equal to 0.3 scores, indicating clinically
meaningful improvement in physical function.
In May 2005, REMICADE was approved in the United States for reducing
signs and symptoms of active arthritis in patients with psoriatic
arthritis. In September of 2004, REMICADE received European Union (EU)
approval, in combination with methotrexate, for the treatment of active and
progressive psoriatic arthritis in patients who have responded inadequately
to disease- modifying anti-rheumatic drugs (DMARDs). Additionally, in May
2006, the Committee for Medicinal Products for Human Use (CHMP) of the
European Medicines Agency gave a positive opinion for the use of REMICADE
for treatment of active and progressive psoriatic arthritis in patients who
have responded inadequately to DMARDs to be used in combination with
methotrexate or alone in patients who show intolerance to methotrexate or
in whom methotrexate is contraindicated. Acceptance of the sBLA filing by
the FDA does not mean that a license has been issued for this indication
nor does it represent any evaluation of the adequacy of the data submitted
in the sBLA.
About IMPACT/IMPACT 2
The Infliximab Multinational Psoriatic Arthritis Controlled Trial
(IMPACT) was a Phase 2b, randomized, double-blind, placebo-controlled study
that involved 104 patients with active psoriatic arthritis (defined as
affecting at least five joints) who failed at least one DMARD. Patients
received either REMICADE (5 mg/kg) or placebo, administered at weeks 0, 2,
6 and 14. The REMICADE group continued on maintenance treatments every
eight weeks through week 94. Beginning at week 16, patients randomized to
the placebo group received an induction regimen of REMICADE followed by
maintenance treatment every eight weeks through week 94. Hands and feet
radiographs were taken at screening and at weeks 50 and 98. Physical
function was measured at multiple visits including screening and at weeks
16, 22, 50 and 94.
REMICADE was generally well tolerated in this study, with one REMICADE
and one placebo patient experiencing serious adverse events (AEs) in the
placebo- controlled portion of the study through week 16. Fourteen patients
out of 104 experienced serious AEs from week 16 through 50 in
placebo/REMICADE crossover and REMICADE groups together. In the second year
of IMPACT, seven patients out of 78 treated with REMICADE were reported
with serious AEs. No deaths, cases of tuberculosis or other opportunistic
infections were reported and serious infections were uncommon. There were
no serious infusion reactions. One patient had a serious AE relating to
malignancy: a ductal adenocarcinoma of the pancreas three months after week
98.
The Induction and Maintenance of Psoriatic Arthritis Clinical Trial 2
(IMPACT 2) was a Phase 3, randomized, double-blind, placebo-controlled
study of 200 patients with active psoriatic arthritis (defined as affecting
at least five joints). The study evaluated the safety and efficacy of
REMICADE in patients who had an inadequate response to DMARDs or
nonsteroidal anti- inflammatory drugs (NSAIDs). Patients received REMICADE
(5 mg/kg) at weeks 0, 2, 6 and every 8 weeks until week 46 or placebo at
weeks 0, 2, 6, 14 and 22. Placebo patients with less than 10 percent
improvement in both swollen and tender joints entered early escape and
received REMICADE at weeks 16, 18 and 22 (n=47). At week 24, placebo
patients who did not qualify for early escape received REMICADE at week 24,
26, 30, 38 and 46. Patients randomized to REMICADE who had less than 20
percent improvement in combined swollen and tender joint count received
REMICADE 10 mg/kg at weeks 38 and 46 (n=15). Patients were allowed
concomitant methotrexate use at a stable dose. Hand and foot radiographs
were taken at week 0, 24 and 54. Physical function was measured at multiple
visits including weeks 0, 14, 24 and 54.
Through 54 weeks, 12 percent of patients in combined REMICADE treatment
groups experienced serious AEs (during average follow-up of 42.8 weeks) as
compared to 6 percent of placebo patients (average follow-up 20.2 weeks).
No deaths, cases of tuberculosis or other opportunistic infections or
serious infusion reactions were reported; serious infections were uncommon.
There were two patients who were reported an AE of malignancy: one case of
basal cell carcinoma in the placebo group and one case of stage I Hodgkin
lymphoma in the REMICADE group. The only laboratory abnormalities that
occurred more frequently with REMICADE compared with placebo were asymptomatic liver
enzyme test elevations. See "Important Safety Information" below.
About Psoriatic Arthritis
Psoriatic arthritis is a chronic inflammatory arthropathy manifesting
with joint pain and swelling that can lead to joint destruction and
debilitation. It is frequently associated with inflamed, scaly, red patches
of skin psoriasis. Symptoms may include stiffness and tenderness of the
joints and surrounding tissue, reduced range of motion, nail changes and
redness and pain of the eye (uveitis). Joints of the hands, wrists, knees,
ankles, feet, lower back and neck are commonly affected. Psoriasis affects
an estimated two to three percent of the world's population, and
approximately one out of three patients affected by psoriasis may develop
psoriatic arthritis. Both men and women are equally affected by psoriatic
arthritis, most commonly between the ages 30 and 50, in the peak of their
productive years.
About REMICADE
REMICADE is the global market leader among anti-tumor necrosis factor
alpha (TNF-alpha) therapies and has demonstrated broad clinical utility in
rheumatoid arthritis (RA), Crohn's disease (CD), psoriatic arthritis (PsA),
ulcerative colitis (UC), ankylosing spondylitis (AS) and pediatric Crohn's
disease (PCD). The safety and efficacy of REMICADE have been well
established in clinical trials over the past 14 years and through
commercial experience with more than 770,000 patients treated worldwide.
In the U.S., REMICADE, in combination with methotrexate, is indicated
for reducing signs and symptoms, inhibiting the progression of structural
damage and improving physical function in patients with moderately to
severely active RA. REMICADE is the only biologic indicated for reducing
signs and symptoms and inducing and maintaining clinical remission in adult
and pediatric patients with moderately to severely active CD who have had
an inadequate response to conventional therapy. REMICADE is also indicated
for reducing the number of draining enterocutaneous and rectovaginal
fistulas and maintaining fistula closure in patients with fistulizing CD.
In December 2004, REMICADE was approved for reducing signs and symptoms in
patients with active AS. In May 2005, REMICADE was approved for reducing
signs and symptoms of active arthritis in patients with PsA. Additionally,
in September 2005, REMICADE was approved for reducing signs and symptoms,
achieving clinical remission and mucosal healing, and eliminating
corticosteroid use in patients with moderately to severely active UC who
have had an inadequate response to conventional therapy. This approval
makes REMICADE the first and only biologic approved for the treatment of
moderate to severe UC. In addition, on May 19, 2006, REMICADE was approved
for reducing signs and symptoms and inducing and maintaining clinical
remission in pediatric patients with moderately to severely active Crohn's
disease who have had an inadequate response to conventional therapy. This
approval establishes REMICADE as the first and only biologic therapy
approved for the treatment of PCD.
REMICADE is unique among available anti-TNF biologic therapies. Unlike
self-administered therapies that require patients to inject themselves
frequently, REMICADE is the only anti-TNF biologic administered directly by
caregivers in the clinic or office setting. In RA (3 mg/kg), CD (5 mg/kg),
PsA (5 mg/kg), UC (5 mg/kg), and PCD (5 mg/kg), REMICADE is a two-hour
infusion administered every 8 weeks, following a standard induction regimen
that requires treatment at weeks 0, 2 and 6. As a result, REMICADE patients
may require as few as six treatments each year. In AS (5 mg/kg), REMICADE
is a two-hour infusion administered every 6 weeks, following a standard
induction regimen that requires treatment at weeks 0, 2 and 6.
Important Safety Information
Many people with heart failure should not take REMICADE; so prior to
treatment you should discuss any heart condition with your doctor. Tell
your doctor right away if you develop new or worsening symptoms of heart
failure (such as shortness of breath or swelling of your ankles or feet).
There are reports of serious infections, including tuberculosis (TB),
sepsis and pneumonia. Some of these infections have been fatal. Tell your
doctor if you have had recent or past exposure to people with TB. Your
doctor will evaluate you for TB and perform a skin test. If you have latent
(inactive) TB, your doctor should begin TB treatment before you start
REMICADE. REMICADE can lower your ability to fight infections, so if you
are prone to or have a history of infections, or develop any signs of an
infection such as fever, fatigue, cough, or the flu while taking REMICADE,
tell your doctor right away. Also tell your doctor if you have lived in a
region where histoplasmosis or coccidioidomycosis is common.
Reports of a type of blood cancer called lymphoma in patients on
REMICADE or other TNF blockers are rare but occur more often than expected
for people in general. People who have been treated for rheumatoid
arthritis, Crohn's disease, ankylosing spondylitis, or psoriatic arthritis
for a long time, particularly those with highly active disease may be more
prone to develop lymphoma. Cancers, other than lymphoma, have also been
reported. Children and young adults who have been treated for Crohn's
disease with REMICADE have developed a rare type of lymphoma that often
results in death. These patients also were receiving drugs known as
azathioprine or 6-mercaptopurine. If you take REMICADE or other TNF
blockers, your risk for developing lymphoma or other cancers may increase.
You should also tell your doctor if you have had or develop lymphoma or
other cancers or if you have a lung disease called chronic obstructive
pulmonary disease (COPD).
There have been rare cases of serious liver injury in people taking
REMICADE, some fatal. Contact your doctor immediately if you develop
symptoms such as jaundice (yellow skin and eyes), dark brown urine,
right-sided abdominal pain, fever, or severe fatigue.
Blood disorders have been reported, some fatal. Tell your doctor if you
develop possible signs of blood disorders such as persistent fever,
bruising, bleeding, or paleness while taking REMICADE. Nervous system
disorders have also been reported. Tell your doctor if you have or have had
a disease that affects the nervous system, or if you experience any
numbness, weakness, tingling, or visual disturbances while taking REMICADE.
Serious infusion reactions have been reported with REMICADE, including
hives, difficulty breathing, and low blood pressure. Reactions have
occurred during or after infusions. In clinical studies, some people
experienced the following common side effects: respiratory infections (that
may include sinus infections and sore throat), coughing, and stomach pain
or mild reactions to infusion such as rash or itchy skin.
Please read important information about REMICADE, including full US
prescribing information, at remicade.
About Centocor
Centocor is harnessing the power of world-leading research and
biomanufacturing to deliver innovative biomedicines that transform
patients' lives. Centocor has already brought innovation to the treatment
of Crohn's disease, rheumatoid arthritis, ankylosing spondylitis, psoriatic
arthritis, ulcerative colitis and pediatric Crohn's disease.
The world leader in monoclonal antibody production and technology,
Centocor has brought critical biologic therapies to patients suffering from
debilitating immune disorders. Centocor, Inc. is a wholly owned subsidiary
of Johnson & Johnson.
Centocor, Inc.
remicade
View drug information on Remicade.
that the US Food and Drug Administration (FDA) has accepted its filing of a
supplemental Biologics License Application (sBLA) for REMICADE(R)
(infliximab) for inhibiting the progression of structural damage and
improving physical function in patients with active psoriatic arthritis
(PsA). The filing is based on one-year data from the double-blind,
placebo-controlled trial IMPACT 2 and two-year data from the double-blind,
placebo-controlled trial IMPACT. PsA is a chronic, progressive and
potentially debilitating disease that causes joint inflammation and is
frequently associated with skin plaques of psoriasis.
"Findings from IMPACT 2 show that early intervention with REMICADE
therapy can significantly inhibit the progression of joint damage, which is
an important factor in the long-term prognosis of patients with psoriatic
arthritis," said Jerome A. Boscia, MD, Senior Vice President, Clinical
Research and Development, Centocor, Inc. "We are encouraged by these data
and are pleased that the FDA has accepted the file for review."
One-year radiographic analyses from IMPACT 2 showed that treatment with
REMICADE resulted in significantly greater inhibition of the progression of
structural damage, compared with placebo (as measured by the change from
baseline in van der Heijde-Sharp [vdH-S] score modified for PsA by adding
measurement for distal interphalangeal joints of the hands). In this method
a higher change in score indicates greater structural damage, while lower
change in score indicates less structural damage. At as early as 24 weeks
of treatment, REMICADE-treated patients experienced a mean change (+/-
standard deviation) in vdH-S score of -0.70 (+/- 2.53) from baseline,
compared with an average change of 0.82 (+/- 2.62) in the placebo group (P
< 0.001). At week 54, patients who received a full 54-week regimen of
REMICADE experienced a mean change of -0.94 (+/- 3.40) from baseline,
compared with an average change of 0.53 (+/- 2.60) in patients who crossed
over from placebo to REMICADE (P = 0.001) at week 16 or 24. Patients
randomized to REMICADE and placebo patients who crossed over to REMICADE
experienced a total improvement of -0.24 (+/- 2.45) and -0.29 (+/- 1.98),
respectively, from week 24 to 54, after all patients switched to treatment
with REMICADE.
REMICADE-treated patients demonstrated significant improvement in
physical function as measured by the Health Assessment Questionnaire (HAQ).
The HAQ assesses the difficulty a patient has accomplishing tasks in eight
functional areas (dressing, arising, eating, walking, hygiene, reaching,
gripping and other activities of daily living). As early as week 14,
patients in the REMICADE group experienced a median improvement of 43
percent, compared with zero percent in the placebo group (P < 0.001), and
results were maintained through one year. At week 54, there was a median 50
percent improvement in HAQ score from baseline in the group randomized to
REMICADE, and a 46 percent improvement in placebo patients who switched to
REMICADE. At week 54, 59 percent of REMICADE randomized patients and 53
percent of placebo patients who crossed over to REMICADE had improvement in
HAQ by greater than or equal to 0.3 scores, indicating clinically
meaningful improvement in physical function.
In May 2005, REMICADE was approved in the United States for reducing
signs and symptoms of active arthritis in patients with psoriatic
arthritis. In September of 2004, REMICADE received European Union (EU)
approval, in combination with methotrexate, for the treatment of active and
progressive psoriatic arthritis in patients who have responded inadequately
to disease- modifying anti-rheumatic drugs (DMARDs). Additionally, in May
2006, the Committee for Medicinal Products for Human Use (CHMP) of the
European Medicines Agency gave a positive opinion for the use of REMICADE
for treatment of active and progressive psoriatic arthritis in patients who
have responded inadequately to DMARDs to be used in combination with
methotrexate or alone in patients who show intolerance to methotrexate or
in whom methotrexate is contraindicated. Acceptance of the sBLA filing by
the FDA does not mean that a license has been issued for this indication
nor does it represent any evaluation of the adequacy of the data submitted
in the sBLA.
About IMPACT/IMPACT 2
The Infliximab Multinational Psoriatic Arthritis Controlled Trial
(IMPACT) was a Phase 2b, randomized, double-blind, placebo-controlled study
that involved 104 patients with active psoriatic arthritis (defined as
affecting at least five joints) who failed at least one DMARD. Patients
received either REMICADE (5 mg/kg) or placebo, administered at weeks 0, 2,
6 and 14. The REMICADE group continued on maintenance treatments every
eight weeks through week 94. Beginning at week 16, patients randomized to
the placebo group received an induction regimen of REMICADE followed by
maintenance treatment every eight weeks through week 94. Hands and feet
radiographs were taken at screening and at weeks 50 and 98. Physical
function was measured at multiple visits including screening and at weeks
16, 22, 50 and 94.
REMICADE was generally well tolerated in this study, with one REMICADE
and one placebo patient experiencing serious adverse events (AEs) in the
placebo- controlled portion of the study through week 16. Fourteen patients
out of 104 experienced serious AEs from week 16 through 50 in
placebo/REMICADE crossover and REMICADE groups together. In the second year
of IMPACT, seven patients out of 78 treated with REMICADE were reported
with serious AEs. No deaths, cases of tuberculosis or other opportunistic
infections were reported and serious infections were uncommon. There were
no serious infusion reactions. One patient had a serious AE relating to
malignancy: a ductal adenocarcinoma of the pancreas three months after week
98.
The Induction and Maintenance of Psoriatic Arthritis Clinical Trial 2
(IMPACT 2) was a Phase 3, randomized, double-blind, placebo-controlled
study of 200 patients with active psoriatic arthritis (defined as affecting
at least five joints). The study evaluated the safety and efficacy of
REMICADE in patients who had an inadequate response to DMARDs or
nonsteroidal anti- inflammatory drugs (NSAIDs). Patients received REMICADE
(5 mg/kg) at weeks 0, 2, 6 and every 8 weeks until week 46 or placebo at
weeks 0, 2, 6, 14 and 22. Placebo patients with less than 10 percent
improvement in both swollen and tender joints entered early escape and
received REMICADE at weeks 16, 18 and 22 (n=47). At week 24, placebo
patients who did not qualify for early escape received REMICADE at week 24,
26, 30, 38 and 46. Patients randomized to REMICADE who had less than 20
percent improvement in combined swollen and tender joint count received
REMICADE 10 mg/kg at weeks 38 and 46 (n=15). Patients were allowed
concomitant methotrexate use at a stable dose. Hand and foot radiographs
were taken at week 0, 24 and 54. Physical function was measured at multiple
visits including weeks 0, 14, 24 and 54.
Through 54 weeks, 12 percent of patients in combined REMICADE treatment
groups experienced serious AEs (during average follow-up of 42.8 weeks) as
compared to 6 percent of placebo patients (average follow-up 20.2 weeks).
No deaths, cases of tuberculosis or other opportunistic infections or
serious infusion reactions were reported; serious infections were uncommon.
There were two patients who were reported an AE of malignancy: one case of
basal cell carcinoma in the placebo group and one case of stage I Hodgkin
lymphoma in the REMICADE group. The only laboratory abnormalities that
occurred more frequently with REMICADE compared with placebo were asymptomatic liver
enzyme test elevations. See "Important Safety Information" below.
About Psoriatic Arthritis
Psoriatic arthritis is a chronic inflammatory arthropathy manifesting
with joint pain and swelling that can lead to joint destruction and
debilitation. It is frequently associated with inflamed, scaly, red patches
of skin psoriasis. Symptoms may include stiffness and tenderness of the
joints and surrounding tissue, reduced range of motion, nail changes and
redness and pain of the eye (uveitis). Joints of the hands, wrists, knees,
ankles, feet, lower back and neck are commonly affected. Psoriasis affects
an estimated two to three percent of the world's population, and
approximately one out of three patients affected by psoriasis may develop
psoriatic arthritis. Both men and women are equally affected by psoriatic
arthritis, most commonly between the ages 30 and 50, in the peak of their
productive years.
About REMICADE
REMICADE is the global market leader among anti-tumor necrosis factor
alpha (TNF-alpha) therapies and has demonstrated broad clinical utility in
rheumatoid arthritis (RA), Crohn's disease (CD), psoriatic arthritis (PsA),
ulcerative colitis (UC), ankylosing spondylitis (AS) and pediatric Crohn's
disease (PCD). The safety and efficacy of REMICADE have been well
established in clinical trials over the past 14 years and through
commercial experience with more than 770,000 patients treated worldwide.
In the U.S., REMICADE, in combination with methotrexate, is indicated
for reducing signs and symptoms, inhibiting the progression of structural
damage and improving physical function in patients with moderately to
severely active RA. REMICADE is the only biologic indicated for reducing
signs and symptoms and inducing and maintaining clinical remission in adult
and pediatric patients with moderately to severely active CD who have had
an inadequate response to conventional therapy. REMICADE is also indicated
for reducing the number of draining enterocutaneous and rectovaginal
fistulas and maintaining fistula closure in patients with fistulizing CD.
In December 2004, REMICADE was approved for reducing signs and symptoms in
patients with active AS. In May 2005, REMICADE was approved for reducing
signs and symptoms of active arthritis in patients with PsA. Additionally,
in September 2005, REMICADE was approved for reducing signs and symptoms,
achieving clinical remission and mucosal healing, and eliminating
corticosteroid use in patients with moderately to severely active UC who
have had an inadequate response to conventional therapy. This approval
makes REMICADE the first and only biologic approved for the treatment of
moderate to severe UC. In addition, on May 19, 2006, REMICADE was approved
for reducing signs and symptoms and inducing and maintaining clinical
remission in pediatric patients with moderately to severely active Crohn's
disease who have had an inadequate response to conventional therapy. This
approval establishes REMICADE as the first and only biologic therapy
approved for the treatment of PCD.
REMICADE is unique among available anti-TNF biologic therapies. Unlike
self-administered therapies that require patients to inject themselves
frequently, REMICADE is the only anti-TNF biologic administered directly by
caregivers in the clinic or office setting. In RA (3 mg/kg), CD (5 mg/kg),
PsA (5 mg/kg), UC (5 mg/kg), and PCD (5 mg/kg), REMICADE is a two-hour
infusion administered every 8 weeks, following a standard induction regimen
that requires treatment at weeks 0, 2 and 6. As a result, REMICADE patients
may require as few as six treatments each year. In AS (5 mg/kg), REMICADE
is a two-hour infusion administered every 6 weeks, following a standard
induction regimen that requires treatment at weeks 0, 2 and 6.
Important Safety Information
Many people with heart failure should not take REMICADE; so prior to
treatment you should discuss any heart condition with your doctor. Tell
your doctor right away if you develop new or worsening symptoms of heart
failure (such as shortness of breath or swelling of your ankles or feet).
There are reports of serious infections, including tuberculosis (TB),
sepsis and pneumonia. Some of these infections have been fatal. Tell your
doctor if you have had recent or past exposure to people with TB. Your
doctor will evaluate you for TB and perform a skin test. If you have latent
(inactive) TB, your doctor should begin TB treatment before you start
REMICADE. REMICADE can lower your ability to fight infections, so if you
are prone to or have a history of infections, or develop any signs of an
infection such as fever, fatigue, cough, or the flu while taking REMICADE,
tell your doctor right away. Also tell your doctor if you have lived in a
region where histoplasmosis or coccidioidomycosis is common.
Reports of a type of blood cancer called lymphoma in patients on
REMICADE or other TNF blockers are rare but occur more often than expected
for people in general. People who have been treated for rheumatoid
arthritis, Crohn's disease, ankylosing spondylitis, or psoriatic arthritis
for a long time, particularly those with highly active disease may be more
prone to develop lymphoma. Cancers, other than lymphoma, have also been
reported. Children and young adults who have been treated for Crohn's
disease with REMICADE have developed a rare type of lymphoma that often
results in death. These patients also were receiving drugs known as
azathioprine or 6-mercaptopurine. If you take REMICADE or other TNF
blockers, your risk for developing lymphoma or other cancers may increase.
You should also tell your doctor if you have had or develop lymphoma or
other cancers or if you have a lung disease called chronic obstructive
pulmonary disease (COPD).
There have been rare cases of serious liver injury in people taking
REMICADE, some fatal. Contact your doctor immediately if you develop
symptoms such as jaundice (yellow skin and eyes), dark brown urine,
right-sided abdominal pain, fever, or severe fatigue.
Blood disorders have been reported, some fatal. Tell your doctor if you
develop possible signs of blood disorders such as persistent fever,
bruising, bleeding, or paleness while taking REMICADE. Nervous system
disorders have also been reported. Tell your doctor if you have or have had
a disease that affects the nervous system, or if you experience any
numbness, weakness, tingling, or visual disturbances while taking REMICADE.
Serious infusion reactions have been reported with REMICADE, including
hives, difficulty breathing, and low blood pressure. Reactions have
occurred during or after infusions. In clinical studies, some people
experienced the following common side effects: respiratory infections (that
may include sinus infections and sore throat), coughing, and stomach pain
or mild reactions to infusion such as rash or itchy skin.
Please read important information about REMICADE, including full US
prescribing information, at remicade.
About Centocor
Centocor is harnessing the power of world-leading research and
biomanufacturing to deliver innovative biomedicines that transform
patients' lives. Centocor has already brought innovation to the treatment
of Crohn's disease, rheumatoid arthritis, ankylosing spondylitis, psoriatic
arthritis, ulcerative colitis and pediatric Crohn's disease.
The world leader in monoclonal antibody production and technology,
Centocor has brought critical biologic therapies to patients suffering from
debilitating immune disorders. Centocor, Inc. is a wholly owned subsidiary
of Johnson & Johnson.
Centocor, Inc.
remicade
View drug information on Remicade.
среда, 15 июня 2011 г.
New BioTrends Report Highlights The Growing Use Of Biologics Among Dermatologists And Rheumatologists In The US
The introduction of
biologic agents has expanded therapeutic options for patients with
Psoriasis, Psoriatic Arthritis (PsA), Rheumatoid Arthritis (RA), and many
other immunologic conditions. BioTrends Research Group, Inc. conducted
primary market research in March 2007 with Dermatologists (n=101) and
Rheumatologists (n=102) practicing in the United States to better
understand how these agents are currently used in clinical practice and how
that use is expected to evolve in the future. According to responses
collected via an on-line survey, a majority of practitioners in both
specialties expect to increase their use of biologic agents in the next six
months.
Among Rheumatologists, the TNF-alpha antagonists (such as Amgen/Wyeth's
Enbrel and Abbott's Humira) are expected to maintain the first line
biologic position, but both Bristol Myers Squibb's Orencia and
Genentech/BiogenIdec's Rituxan are expected to post market share gains as
physicians become more familiar with these agents and treat more
aggressively. Enbrel is the preferred biologic for the treatment of RA, but
a higher percent of the surveyed Rheumatologists indicate a preference for
Humira when treating PsA based on the perception that Humira has "superior
skin data." Although a majority of these rheumatologists would be most
likely to initiate Orencia or Rituxan after the patient had failed two
TNF-alpha antagonists, 66% would consider Orencia and 48% would consider
Rituxan after a DMARD failure.
Dermatologists, while overwhelmingly loyal to Enbrel, report a growing
use of Abbott's Humira. Less than half of the dermatologists surveyed
currently use Humira, however, in the next six months 64% expect to use the
product. Furthermore, 15% of the respondents choose Humira as their
preferred first line biologic to treat PsA and with a psoriasis approval
expected in the next few months, use of Humira can be expected to expand
further among dermatologists. Centocor's Remicade was also recently
approved for its first dermatological indication and although 13% of the
dermatologists expect to increase their use of Remicade, only one-third of
the dermatologists are currently using the product. In-office infusion of
Remicade by dermatologists will remain limited due to
stocking/administering logistics, liability concerns, and reimbursement
issues. Finally, use of the T-cell inhibitors (Astellas' Amevive and
Genentech/Xoma's Raptiva) remains low and stagnant. Currently, more than
50% of the surveyed dermatologists do not use either of these products.
On the horizon are several new biologics such as Centocor's CNTO-148
(golimumab) and CNTO-1275, Roche's Actemra (tocilizumab), and UCB Pharma's
Cimzia (certolizumab pegol) and although physicians report a low level of
familiarity with products in development, their interest level in new
treatment options is extremely high. The ideal agent? More than half of the
respondents suggest that an oral biologic, if approved, would become their
preferred first line biologic.
About BioTrends Research Group, Inc.
BioTrends Research Group, Inc. (bio-trends) provides syndicated
and custom market research to pharmaceutical manufactures competing in
clinically evolving, specialty pharmaceutical markets.
All company, brand, or product names contained in this document may be
trademarks of their respective holders.
BioTrends Research Group, Inc.
bio-trends
View drug information on Actemra; Amevive; Cimzia.
biologic agents has expanded therapeutic options for patients with
Psoriasis, Psoriatic Arthritis (PsA), Rheumatoid Arthritis (RA), and many
other immunologic conditions. BioTrends Research Group, Inc. conducted
primary market research in March 2007 with Dermatologists (n=101) and
Rheumatologists (n=102) practicing in the United States to better
understand how these agents are currently used in clinical practice and how
that use is expected to evolve in the future. According to responses
collected via an on-line survey, a majority of practitioners in both
specialties expect to increase their use of biologic agents in the next six
months.
Among Rheumatologists, the TNF-alpha antagonists (such as Amgen/Wyeth's
Enbrel and Abbott's Humira) are expected to maintain the first line
biologic position, but both Bristol Myers Squibb's Orencia and
Genentech/BiogenIdec's Rituxan are expected to post market share gains as
physicians become more familiar with these agents and treat more
aggressively. Enbrel is the preferred biologic for the treatment of RA, but
a higher percent of the surveyed Rheumatologists indicate a preference for
Humira when treating PsA based on the perception that Humira has "superior
skin data." Although a majority of these rheumatologists would be most
likely to initiate Orencia or Rituxan after the patient had failed two
TNF-alpha antagonists, 66% would consider Orencia and 48% would consider
Rituxan after a DMARD failure.
Dermatologists, while overwhelmingly loyal to Enbrel, report a growing
use of Abbott's Humira. Less than half of the dermatologists surveyed
currently use Humira, however, in the next six months 64% expect to use the
product. Furthermore, 15% of the respondents choose Humira as their
preferred first line biologic to treat PsA and with a psoriasis approval
expected in the next few months, use of Humira can be expected to expand
further among dermatologists. Centocor's Remicade was also recently
approved for its first dermatological indication and although 13% of the
dermatologists expect to increase their use of Remicade, only one-third of
the dermatologists are currently using the product. In-office infusion of
Remicade by dermatologists will remain limited due to
stocking/administering logistics, liability concerns, and reimbursement
issues. Finally, use of the T-cell inhibitors (Astellas' Amevive and
Genentech/Xoma's Raptiva) remains low and stagnant. Currently, more than
50% of the surveyed dermatologists do not use either of these products.
On the horizon are several new biologics such as Centocor's CNTO-148
(golimumab) and CNTO-1275, Roche's Actemra (tocilizumab), and UCB Pharma's
Cimzia (certolizumab pegol) and although physicians report a low level of
familiarity with products in development, their interest level in new
treatment options is extremely high. The ideal agent? More than half of the
respondents suggest that an oral biologic, if approved, would become their
preferred first line biologic.
About BioTrends Research Group, Inc.
BioTrends Research Group, Inc. (bio-trends) provides syndicated
and custom market research to pharmaceutical manufactures competing in
clinically evolving, specialty pharmaceutical markets.
All company, brand, or product names contained in this document may be
trademarks of their respective holders.
BioTrends Research Group, Inc.
bio-trends
View drug information on Actemra; Amevive; Cimzia.
вторник, 14 июня 2011 г.
The Function Of The Protein CD20
Antibodies directed against the protein CD20, which is expressed by immune cells known as B cells, are used to treat B cell non-Hodgkin lymphoma and rheumatoid arthritis. Despite this, the function of CD20 has not been determined. Now, a team of researchers led by Ren?© van Lier, at the Academic Medical Center, The Netherlands, has determined that CD20 has a nonredundant role in generating optimal B cell immune responses by analyzing a patient lacking the protein.
The patient was referred to the Academic Medical Center at four years of age, with a history of intermittent respiratory infections and recurrent bronchopneumonia. Detailed analysis of immune cells from the patient revealed that the B cells lacked CD20 expression due to a mutation in the CD20 gene. These CD20-deficient B cells failed to respond normally to certain stimuli in vitro, specifically those known as T-independent antigens. Further, vaccination of the patient with a T-independent antigen led to a markedly impaired B cell response. The authors therefore conclude that CD20 has an important role in enabling B cells to respond optimally to T-independent antigens and that absence of this protein causes an immunodeficiency characterized by a reduced capacity to make B cell responses to T-independent antigens.
TITLE: CD20 deficiency in humans results in impaired T cell-independent antibody responses
AUTHOR: Ren?© A.W. van Lier, Academic Medical Center, Amsterdam, The Netherlands.
JCI online December 21, 2009
Source: Karen Honey
Journal of Clinical Investigation
The patient was referred to the Academic Medical Center at four years of age, with a history of intermittent respiratory infections and recurrent bronchopneumonia. Detailed analysis of immune cells from the patient revealed that the B cells lacked CD20 expression due to a mutation in the CD20 gene. These CD20-deficient B cells failed to respond normally to certain stimuli in vitro, specifically those known as T-independent antigens. Further, vaccination of the patient with a T-independent antigen led to a markedly impaired B cell response. The authors therefore conclude that CD20 has an important role in enabling B cells to respond optimally to T-independent antigens and that absence of this protein causes an immunodeficiency characterized by a reduced capacity to make B cell responses to T-independent antigens.
TITLE: CD20 deficiency in humans results in impaired T cell-independent antibody responses
AUTHOR: Ren?© A.W. van Lier, Academic Medical Center, Amsterdam, The Netherlands.
JCI online December 21, 2009
Source: Karen Honey
Journal of Clinical Investigation
понедельник, 13 июня 2011 г.
Fighting Gum Disease With Gene Therapy
Scientists at the University of Michigan have shown that gene therapy can be used to successfully stop the development of periodontal disease, the leading cause of tooth loss in adults.
The findings will be published online Dec 11 in advance of print publication in Gene Therapy.
Using gene transfer to treat life threatening conditions is not new, but the U-M group is the first known to use the gene delivery approach to show potential in treating chronic conditions such as periodontal disease, said William Giannobile, professor at the U-M School of Dentistry and principal investigator on the study.
"Gene therapy has not been used in non-life threatening disease. (Periodontal disease) is more disabling than life threatening," said Giannobile, who also directs the Michigan Center for Oral Health Research and has an appointment in the U-M College of Engineering. "This is so important because the next wave of improving medical therapeutics goes beyond saving life, and moves forward to improving the quality of life."
The preclinical study offers was a collaboration with the Seattle-based biotechnology company Targeted Genetics. In July, Targeted Genetics released human trial results that showed the same gene therapy approach used to stop periodontal disease had positive affects in human patients with rheumatoid arthritis, another chronic, non-life threatening, disabling condition. The company tested 127 human subjects and showed a 30 percent improvement in pain relief, and gain of function, among other enhancements using the gene treatment.
People with rheumatoid arthritis are four times more likely to also be afflicted with periodontitis. Periodontal disease is also linked to systemic conditions such as heart disease, bacterial pneumonia and stroke, likely due to the spread of bacteria coming from the oral cavity that invade other parts of the body.
Using gene therapy, Giannobile's group found a way to help certain cells using an inactivated virus to produce more of a naturally-produced molecule soluble TNF receptor. This factor is under-produced in patients with periodontitis. The molecule delivered by gene therapy works like a sponge to sop up excessive levels of tumor necrosis factor, a molecule known to worsen inflammatory bone destruction in patients afflicted with rheumatoid arthritis, joint deterioration and periodontitis.
The gene also delivers quite a bit of genetic bang for the buck. The periodontal tissues were spared from destruction by more than 60-80 percent with the use of gene therapy.
"If you deliver the gene into the target cells once, it keeps producing in the cells for a very long period of time or potentially for the life of the patient," Giannobile said. "This therapy is basically a single administration, but it could have potentially life-long treatment effects in patients who are at risk for severe disease activity."
The next step is additional safety testing on periodontal patients, he said.
The research was funded by the National Institutes of Health. Co-authors included Haim Burstein, a research scientist at Targeted Genetics Corporation, and members of U-M research team Joni Cirelli, Chan Ho Park, Jim Sugai and Katie MacKool.
For more on Giannobile, visit:
ns.umich/htdocs/public/experts/ExpDisplay.php?ExpID=286
U-M Dentistry:
dent.umich/
Source: Laura Bailey
University of Michigan
The findings will be published online Dec 11 in advance of print publication in Gene Therapy.
Using gene transfer to treat life threatening conditions is not new, but the U-M group is the first known to use the gene delivery approach to show potential in treating chronic conditions such as periodontal disease, said William Giannobile, professor at the U-M School of Dentistry and principal investigator on the study.
"Gene therapy has not been used in non-life threatening disease. (Periodontal disease) is more disabling than life threatening," said Giannobile, who also directs the Michigan Center for Oral Health Research and has an appointment in the U-M College of Engineering. "This is so important because the next wave of improving medical therapeutics goes beyond saving life, and moves forward to improving the quality of life."
The preclinical study offers was a collaboration with the Seattle-based biotechnology company Targeted Genetics. In July, Targeted Genetics released human trial results that showed the same gene therapy approach used to stop periodontal disease had positive affects in human patients with rheumatoid arthritis, another chronic, non-life threatening, disabling condition. The company tested 127 human subjects and showed a 30 percent improvement in pain relief, and gain of function, among other enhancements using the gene treatment.
People with rheumatoid arthritis are four times more likely to also be afflicted with periodontitis. Periodontal disease is also linked to systemic conditions such as heart disease, bacterial pneumonia and stroke, likely due to the spread of bacteria coming from the oral cavity that invade other parts of the body.
Using gene therapy, Giannobile's group found a way to help certain cells using an inactivated virus to produce more of a naturally-produced molecule soluble TNF receptor. This factor is under-produced in patients with periodontitis. The molecule delivered by gene therapy works like a sponge to sop up excessive levels of tumor necrosis factor, a molecule known to worsen inflammatory bone destruction in patients afflicted with rheumatoid arthritis, joint deterioration and periodontitis.
The gene also delivers quite a bit of genetic bang for the buck. The periodontal tissues were spared from destruction by more than 60-80 percent with the use of gene therapy.
"If you deliver the gene into the target cells once, it keeps producing in the cells for a very long period of time or potentially for the life of the patient," Giannobile said. "This therapy is basically a single administration, but it could have potentially life-long treatment effects in patients who are at risk for severe disease activity."
The next step is additional safety testing on periodontal patients, he said.
The research was funded by the National Institutes of Health. Co-authors included Haim Burstein, a research scientist at Targeted Genetics Corporation, and members of U-M research team Joni Cirelli, Chan Ho Park, Jim Sugai and Katie MacKool.
For more on Giannobile, visit:
ns.umich/htdocs/public/experts/ExpDisplay.php?ExpID=286
U-M Dentistry:
dent.umich/
Source: Laura Bailey
University of Michigan
воскресенье, 12 июня 2011 г.
Ferring Pharmaceuticals Unveils Six-Month Efficacy Data For EUFLEXXA(R) For The Treatment Of Osteoarthritis Knee Pain
Ferring Pharmaceuticals recently presented the results of a six-month safety and efficacy study demonstrating that EUFLEXXA(R) (1% sodium hyaluronate) was effective at decreasing the pain of knee osteoarthritis (OA) at 26 weeks. The study showed that EUFLEXXA (R) is superior to saline in decreasing pain at 26 weeks in patients with OA of the knee.(1) The study results were presented by Dr. Roy D. Altman in a poster at the Annual Meeting of the American Academy of Orthopedic Surgeons on February 23, 2009.
EUFLEXXA(R) is a three-injection treatment regimen indicated for patients who have failed to respond adequately to conservative non-pharmacologic therapy and simple analgesics. The goal of hyaluronic acid (HA) therapy is to reduce pain and improve physical function by replenishing the HA in human synovial fluid (fluid in joints). In OA, this fluid becomes thinner, leading to a decrease in elasticity and viscosity.
About the Study
The multicenter, 26-week, randomized, double-blind trial compared EUFLEXXA(R) and intra-articular buffered saline (IA-SA) for level of pain following a 50-Foot Walk Test, measured by 100 mm visual analog scale (VAS). The 586 patients with chronic idiopathic knee OA were randomized to treatment with either product in a 1:1 ratio. Each patient received one weekly injection for 3 weeks with 9 follow-up visits over 26 weeks after the first injection.
The EUFLEXXA(R) group showed an advantage over saline in pain reduction, with a larger mean decrease from baseline in pain scores: -25.7 (28.9) mm versus -18.5(32.5) mm respectively, with a least squares means of -6.6 mm (P=0.002). At 26 weeks, 145 (58%) of EUFLEXXA(R) subjects reported a greater than or equal to 20-mm improvement in pain based on the VAS scoring, compared with 120 (46%) in the other group (P=0.006). The percentage of Osteoarthritis Research Society International (OARSI) responders for the EUFLEXXA(R) group was also significantly greater than that in the other group (67% versus 59% (P=0.047). A subject is considered a responder if there is a high improvement in pain or function, or improvement in at least two of the following three categories: pain greater than or equal to 20% and absolute change greater than or equal to 10 mm, function greater than or equal to 20% and absolute change greater than or equal to 10 mm, and/or patient global assessment greater than or equal to 20% and absolute change.
About EUFLEXXA(R)
EUFLEXXA(R) (1% sodium hyaluronate) is the first non-avian derived* hyaluronic acid (HA) approved in the U.S. for treatment of knee pain due to osteoarthritis (OA). EUFLEXXA(R) is indicated for patients who have failed to get adequate pain relief either from simple pain medications, such as acetaminophen, or from exercise and/or physical therapy. The process used to manufacture EUFLEXXA(R) results in highly-purified HA with properties similar to the HA in healthy human synovial fluid.(2-4) EUFLEXXA(R) received approval from the U.S. Food and Drug Administration (FDA) on December 3, 2004, and became available to the public on November 8, 2005.
EUFLEXXA(R) should not be used in people who have had any previous allergic reaction to hyaluronate preparations or who have knee joint infections or skin diseases in the area of the injection site. Common adverse events reported were arthralgia (joint pain) and back pain. Temporary knee pain and swelling may occur after injection. Strict aseptic technique must be followed to avoid joint infection.
About Ferring Pharmaceuticals Inc.
Ferring Pharmaceuticals Inc. is a subsidiary of Ferring Pharmaceuticals, a privately owned, international pharmaceutical company. Ferring Pharmaceuticals offers a line of infertility, urology, and orthopaedic products in the U.S. market. They include: BRAVELLE(R) (urofollitropin for injection, purified), MENOPUR(R) and REPRONEX(R) (menotropins for injection, USP), Novarel(R) (chorionic gonadotropin for injection, USP), ENDOMETRIN(R) (progesterone) Vaginal Insert, 100 mg, PROSED(R) DS (methenamine, phenyl salicylate, methylene blue, benzoic acid, hyoscyamine sulfate), DESMOPRESSIN, DEGARELIX for injection and EUFLEXXA(R) (1% sodium hyaluronate).
References
(1) Data on File, Ferring Pharmaceuticals
(2) Altman RD, Rosen JE. Six-month safety and efficacy of non-avian intra-articular hyaluronan in knee osteoarthritis (OA).
(3) Schiavinato A, Finesso M, Cortivo R, & Abatangelo G (2002). Comparison of the effects of intra-articular injections of Hyaluronan and its chemically cross-linked derivative (Hylan G-F20) in normal rabbit knee joints. Clin Exp Rheumatol 20, 445-454.
(4) Goomer RS, Leslie K, Maris T, & Amiel D (2005). Native hyaluronan produces less hypersensitivity than cross-linked hyaluronan. Clin Orthop Relat Res 239-245.
Source: Ferring Pharmaceuticals Inc
View drug information on Degarelix; Desmopressin Acetate.
EUFLEXXA(R) is a three-injection treatment regimen indicated for patients who have failed to respond adequately to conservative non-pharmacologic therapy and simple analgesics. The goal of hyaluronic acid (HA) therapy is to reduce pain and improve physical function by replenishing the HA in human synovial fluid (fluid in joints). In OA, this fluid becomes thinner, leading to a decrease in elasticity and viscosity.
About the Study
The multicenter, 26-week, randomized, double-blind trial compared EUFLEXXA(R) and intra-articular buffered saline (IA-SA) for level of pain following a 50-Foot Walk Test, measured by 100 mm visual analog scale (VAS). The 586 patients with chronic idiopathic knee OA were randomized to treatment with either product in a 1:1 ratio. Each patient received one weekly injection for 3 weeks with 9 follow-up visits over 26 weeks after the first injection.
The EUFLEXXA(R) group showed an advantage over saline in pain reduction, with a larger mean decrease from baseline in pain scores: -25.7 (28.9) mm versus -18.5(32.5) mm respectively, with a least squares means of -6.6 mm (P=0.002). At 26 weeks, 145 (58%) of EUFLEXXA(R) subjects reported a greater than or equal to 20-mm improvement in pain based on the VAS scoring, compared with 120 (46%) in the other group (P=0.006). The percentage of Osteoarthritis Research Society International (OARSI) responders for the EUFLEXXA(R) group was also significantly greater than that in the other group (67% versus 59% (P=0.047). A subject is considered a responder if there is a high improvement in pain or function, or improvement in at least two of the following three categories: pain greater than or equal to 20% and absolute change greater than or equal to 10 mm, function greater than or equal to 20% and absolute change greater than or equal to 10 mm, and/or patient global assessment greater than or equal to 20% and absolute change.
About EUFLEXXA(R)
EUFLEXXA(R) (1% sodium hyaluronate) is the first non-avian derived* hyaluronic acid (HA) approved in the U.S. for treatment of knee pain due to osteoarthritis (OA). EUFLEXXA(R) is indicated for patients who have failed to get adequate pain relief either from simple pain medications, such as acetaminophen, or from exercise and/or physical therapy. The process used to manufacture EUFLEXXA(R) results in highly-purified HA with properties similar to the HA in healthy human synovial fluid.(2-4) EUFLEXXA(R) received approval from the U.S. Food and Drug Administration (FDA) on December 3, 2004, and became available to the public on November 8, 2005.
EUFLEXXA(R) should not be used in people who have had any previous allergic reaction to hyaluronate preparations or who have knee joint infections or skin diseases in the area of the injection site. Common adverse events reported were arthralgia (joint pain) and back pain. Temporary knee pain and swelling may occur after injection. Strict aseptic technique must be followed to avoid joint infection.
About Ferring Pharmaceuticals Inc.
Ferring Pharmaceuticals Inc. is a subsidiary of Ferring Pharmaceuticals, a privately owned, international pharmaceutical company. Ferring Pharmaceuticals offers a line of infertility, urology, and orthopaedic products in the U.S. market. They include: BRAVELLE(R) (urofollitropin for injection, purified), MENOPUR(R) and REPRONEX(R) (menotropins for injection, USP), Novarel(R) (chorionic gonadotropin for injection, USP), ENDOMETRIN(R) (progesterone) Vaginal Insert, 100 mg, PROSED(R) DS (methenamine, phenyl salicylate, methylene blue, benzoic acid, hyoscyamine sulfate), DESMOPRESSIN, DEGARELIX for injection and EUFLEXXA(R) (1% sodium hyaluronate).
References
(1) Data on File, Ferring Pharmaceuticals
(2) Altman RD, Rosen JE. Six-month safety and efficacy of non-avian intra-articular hyaluronan in knee osteoarthritis (OA).
(3) Schiavinato A, Finesso M, Cortivo R, & Abatangelo G (2002). Comparison of the effects of intra-articular injections of Hyaluronan and its chemically cross-linked derivative (Hylan G-F20) in normal rabbit knee joints. Clin Exp Rheumatol 20, 445-454.
(4) Goomer RS, Leslie K, Maris T, & Amiel D (2005). Native hyaluronan produces less hypersensitivity than cross-linked hyaluronan. Clin Orthop Relat Res 239-245.
Source: Ferring Pharmaceuticals Inc
View drug information on Degarelix; Desmopressin Acetate.
суббота, 11 июня 2011 г.
New Way To Fight Inflammation Discovered At Oxford
Researchers at the University of Oxford have discovered a series of new peptide molecules that have potential as treatments of inflammatory disorders, including endotoxic shock, inflammatory bowel disease, rheumatoid arthritis, uveitis and atherosclerosis.
The peptides work by reducing the production of inflammatory cytokines, signaling proteins which play an important role in the body's response to infection and injury, but are also implicated in excessive immune responses in inflammatory diseases.
Dr David Greaves, at the University of Oxford's Sir William Dunn School of Pathology, said his group's work could provide a new approach to developing treatments for chronic inflammation:
"All the drugs that we currently have for treating inflammation target pro-inflammatory molecules, and all have side-effects, essentially they're dampening down pro-inflammatory signals, not controlling the underlying inflammation.
"Our approach taps into the body's naturally occurring anti-inflammatory mechanism."
The peptides work by inhibiting activated macrophages via the G protein-coupled receptor (GPCR), ChemR23 - substantially reducing the production of inflammatory cytokines TNF?±, MCP-1, IL-6 and IL-1??.
In addition, the same peptides dramatically enhance clearance of pathogens, potentially speeding up the body's ability to recover from inflammation. This might be important for treatment of diseases such as age-related macular degeneration and Alzheimer's disease.
The Greaves lab has established that the peptides exhibit potent anti-inflammatory activity in pre-clinical models of inflammation.
"The attraction of these peptides is that they're active at very low concentrations (picomolar), and they have a great deal of promise for use as new therapeutic drugs," said Greaves.
The work recently formed the basis of a paper published in the Journal of Experimental Medicine (Cash et al, 2008).
This work is the subject of a patent application, and Isis would like to talk to companies interested in developing the peptides as new therapeutics.
isis-innovation
The peptides work by reducing the production of inflammatory cytokines, signaling proteins which play an important role in the body's response to infection and injury, but are also implicated in excessive immune responses in inflammatory diseases.
Dr David Greaves, at the University of Oxford's Sir William Dunn School of Pathology, said his group's work could provide a new approach to developing treatments for chronic inflammation:
"All the drugs that we currently have for treating inflammation target pro-inflammatory molecules, and all have side-effects, essentially they're dampening down pro-inflammatory signals, not controlling the underlying inflammation.
"Our approach taps into the body's naturally occurring anti-inflammatory mechanism."
The peptides work by inhibiting activated macrophages via the G protein-coupled receptor (GPCR), ChemR23 - substantially reducing the production of inflammatory cytokines TNF?±, MCP-1, IL-6 and IL-1??.
In addition, the same peptides dramatically enhance clearance of pathogens, potentially speeding up the body's ability to recover from inflammation. This might be important for treatment of diseases such as age-related macular degeneration and Alzheimer's disease.
The Greaves lab has established that the peptides exhibit potent anti-inflammatory activity in pre-clinical models of inflammation.
"The attraction of these peptides is that they're active at very low concentrations (picomolar), and they have a great deal of promise for use as new therapeutic drugs," said Greaves.
The work recently formed the basis of a paper published in the Journal of Experimental Medicine (Cash et al, 2008).
This work is the subject of a patent application, and Isis would like to talk to companies interested in developing the peptides as new therapeutics.
isis-innovation
пятница, 10 июня 2011 г.
Savient Announces FDA's Advisory Panel To Review Pegloticase For Treatment Failure Gout Patients
Savient Pharmaceuticals, Inc. (Nasdaq: SVNT) announced that its biologics license application (BLA) for pegloticase for treatment-failure gout will be reviewed by the Arthritis Advisory Committee appointed by the U.S. Food and Drug Administration (FDA) on March 5, 2009 as required for a drug of a new therapeutic class.
Savient submitted its BLA to the FDA on October 31, 2008 seeking approval to market pegloticase in the United States. On December 29, 2008, the FDA accepted the BLA filing for review and granted priority review. A priority review is an FDA designation that is assigned to products that if approved, would provide a significant improvement in the safety or effectiveness of the treatment, diagnosis or prevention of a serious or life-threatening disease. Under priority review, the target date for an FDA decision on the pegloticase BLA is April 30, 2009.
Savient's filing includes data from both the six-month placebo-controlled Phase 3 pivotal trials, as well as data from the open label extension (OLE) study. The two replicate six-month Phase 3 clinical trials for pegloticase were performed under the auspices of a Special Protocol Assessment (SPA) (2006). Pegloticase was granted orphan drug designation by the FDA in 2001.
ABOUT SAVIENT PHARMACEUTICALS, INC.
Savient Pharmaceuticals, Inc. is a biopharmaceutical company engaged in developing and distributing pharmaceutical products that target unmet medical needs in both niche and broader markets. The Company's product development candidate, pegloticase for treatment-failure gout, has reported positive Phase 1, 2 and 3 clinical data. Patient dosing in the Phase 3 clinical studies began in June 2006; patient enrollment was completed in March 2007; and the Phase 3 clinical studies were completed in October 2007 and the BLA was filed with the FDA in October 2008. Savient has exclusively licensed worldwide rights to the technology related to pegloticase, formerly referred to as Puricase(R), from Duke University and Mountain View Pharmaceuticals, Inc. Savient's experienced management team is committed to advancing its pipeline and expanding its product portfolio by in-licensing late-stage compounds and exploring co-promotion and co-development opportunities that fit the Company's expertise in specialty pharmaceuticals and biopharmaceuticals with an initial focus in rheumatology. Savient also manufactures and supplies Oxandrin(R) (oxandrolone tablets, USP) CIII in the U.S. Puricase is a registered trademark of Mountain View Pharmaceuticals, Inc. Further information on Savient can be accessed by visiting: savient.
FORWARD LOOKING LANGUAGE
All statements other than statements of historical facts included in this press release are forward-looking statements that are subject to certain risks, trends and uncertainties that could cause actual results and achievements to differ materially from those expressed in such statements. These risks, trends and uncertainties are in some instances beyond our control. Words such as "anticipate," "believe," "estimate," "expect," "intend," "plan," "will" and other similar expressions help identify forward-looking statements, although not all forward-looking statements contain these identifying words. In particular, any statements regarding the efficacy and safety of pegloticase, our BLA filing with the FDA, the Advisory Committee, approval of the BLA, preparation for commercialization of pegloticase, and the market for pegloticase, are forward-looking statements. These forward-looking statements involve substantial risks and uncertainties and are based on our assessment and interpretation of the currently available data and information, our Phase 3 clinical data and on current expectations, assumptions, estimates and projections about our business and the biopharmaceutical and specialty pharmaceutical industries in which we operate. Important factors that may affect our ability to achieve the matters addressed in these forward-looking statements include, but are not limited to, the delay or failure in completing development of pegloticase and developing other product candidates; our stock price and market conditions; varying interpretations of our clinical and CMC data by the FDA; delay achieving or failure to achieve FDA approval of pegloticase; inability to manufacture commercial quantities of our products; inability to gain market acceptance sufficient to justify development and commercialization costs if our products are approved for marketing; our continuing to incur substantial net losses for the foreseeable future; difficulties in obtaining financing; potential development of alternative or more effective products by competitors; reliance on third parties to manufacture, market and distribute many of our products; economic, political and other risks associated with foreign operations; risks of maintaining protection for our intellectual property; risks of an adverse determination in ongoing or future intellectual property litigation; and risks associated with stringent government regulation of the biopharmaceutical industry and other important factors set forth more fully in our reports filed with the Securities and Exchange Commission, to which investors are referred for further information. We may not actually achieve the plans, intentions or expectations disclosed in our forward-looking statements, and you should not place undue reliance on our forward-looking statements which speak only as of the date of publication of this press release to shareholders. Actual results or events could differ materially from the plans, intentions and expectations disclosed in the forward-looking statements that we make. Our forward-looking statements do not reflect the potential impact of any future acquisitions, mergers, dispositions, joint ventures or investments that we may make. We do not have a policy of updating or revising forward-looking statements and, except as required by law, assume no obligation to update any forward-looking statements.
Savient Pharmaceuticals, Inc.
savient
Savient submitted its BLA to the FDA on October 31, 2008 seeking approval to market pegloticase in the United States. On December 29, 2008, the FDA accepted the BLA filing for review and granted priority review. A priority review is an FDA designation that is assigned to products that if approved, would provide a significant improvement in the safety or effectiveness of the treatment, diagnosis or prevention of a serious or life-threatening disease. Under priority review, the target date for an FDA decision on the pegloticase BLA is April 30, 2009.
Savient's filing includes data from both the six-month placebo-controlled Phase 3 pivotal trials, as well as data from the open label extension (OLE) study. The two replicate six-month Phase 3 clinical trials for pegloticase were performed under the auspices of a Special Protocol Assessment (SPA) (2006). Pegloticase was granted orphan drug designation by the FDA in 2001.
ABOUT SAVIENT PHARMACEUTICALS, INC.
Savient Pharmaceuticals, Inc. is a biopharmaceutical company engaged in developing and distributing pharmaceutical products that target unmet medical needs in both niche and broader markets. The Company's product development candidate, pegloticase for treatment-failure gout, has reported positive Phase 1, 2 and 3 clinical data. Patient dosing in the Phase 3 clinical studies began in June 2006; patient enrollment was completed in March 2007; and the Phase 3 clinical studies were completed in October 2007 and the BLA was filed with the FDA in October 2008. Savient has exclusively licensed worldwide rights to the technology related to pegloticase, formerly referred to as Puricase(R), from Duke University and Mountain View Pharmaceuticals, Inc. Savient's experienced management team is committed to advancing its pipeline and expanding its product portfolio by in-licensing late-stage compounds and exploring co-promotion and co-development opportunities that fit the Company's expertise in specialty pharmaceuticals and biopharmaceuticals with an initial focus in rheumatology. Savient also manufactures and supplies Oxandrin(R) (oxandrolone tablets, USP) CIII in the U.S. Puricase is a registered trademark of Mountain View Pharmaceuticals, Inc. Further information on Savient can be accessed by visiting: savient.
FORWARD LOOKING LANGUAGE
All statements other than statements of historical facts included in this press release are forward-looking statements that are subject to certain risks, trends and uncertainties that could cause actual results and achievements to differ materially from those expressed in such statements. These risks, trends and uncertainties are in some instances beyond our control. Words such as "anticipate," "believe," "estimate," "expect," "intend," "plan," "will" and other similar expressions help identify forward-looking statements, although not all forward-looking statements contain these identifying words. In particular, any statements regarding the efficacy and safety of pegloticase, our BLA filing with the FDA, the Advisory Committee, approval of the BLA, preparation for commercialization of pegloticase, and the market for pegloticase, are forward-looking statements. These forward-looking statements involve substantial risks and uncertainties and are based on our assessment and interpretation of the currently available data and information, our Phase 3 clinical data and on current expectations, assumptions, estimates and projections about our business and the biopharmaceutical and specialty pharmaceutical industries in which we operate. Important factors that may affect our ability to achieve the matters addressed in these forward-looking statements include, but are not limited to, the delay or failure in completing development of pegloticase and developing other product candidates; our stock price and market conditions; varying interpretations of our clinical and CMC data by the FDA; delay achieving or failure to achieve FDA approval of pegloticase; inability to manufacture commercial quantities of our products; inability to gain market acceptance sufficient to justify development and commercialization costs if our products are approved for marketing; our continuing to incur substantial net losses for the foreseeable future; difficulties in obtaining financing; potential development of alternative or more effective products by competitors; reliance on third parties to manufacture, market and distribute many of our products; economic, political and other risks associated with foreign operations; risks of maintaining protection for our intellectual property; risks of an adverse determination in ongoing or future intellectual property litigation; and risks associated with stringent government regulation of the biopharmaceutical industry and other important factors set forth more fully in our reports filed with the Securities and Exchange Commission, to which investors are referred for further information. We may not actually achieve the plans, intentions or expectations disclosed in our forward-looking statements, and you should not place undue reliance on our forward-looking statements which speak only as of the date of publication of this press release to shareholders. Actual results or events could differ materially from the plans, intentions and expectations disclosed in the forward-looking statements that we make. Our forward-looking statements do not reflect the potential impact of any future acquisitions, mergers, dispositions, joint ventures or investments that we may make. We do not have a policy of updating or revising forward-looking statements and, except as required by law, assume no obligation to update any forward-looking statements.
Savient Pharmaceuticals, Inc.
savient
четверг, 9 июня 2011 г.
Researchers Identify Disease Mechanism Underlying Rheumatoid Arthritis
Investigators at LA BioMed have identified a novel disease mechanism underlying rheumatoid arthritis that may open the door to new therapies for this and other debilitating autoimmune disorders.
In an article appearing in the September 1 issue of the Journal of Immunology, principal investigator Terry J. Smith, MD describes research that identifies an interaction between antibodies found in patients with rheumatoid arthritis and the insulin-like growth factor receptor (IGF-1R) as a cause of inflammation and lymphocyte infiltration.
According to Dr. Smith, "It is possible that these findings will allow us for the first time to interrupt the disease process before any lasting damage occurs."
Rheumatoid arthritis is one of several autoimmune disorders in which cellular defense mechanisms identify the body's own tissues as foreign and seek to destroy them. Other autoimmune disorders include such ailments as Graves' disease, multiple sclerosis and lupus. This research suggests that there could be a common therapeutic strategy for these conditions.
To speak to Dr. Smith, contact David Feuerherd at dfissuesmanagement.
Contact: David Feuerherd
dfissuesmanagement
310-215-0234
Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center (LA BioMed)
In an article appearing in the September 1 issue of the Journal of Immunology, principal investigator Terry J. Smith, MD describes research that identifies an interaction between antibodies found in patients with rheumatoid arthritis and the insulin-like growth factor receptor (IGF-1R) as a cause of inflammation and lymphocyte infiltration.
According to Dr. Smith, "It is possible that these findings will allow us for the first time to interrupt the disease process before any lasting damage occurs."
Rheumatoid arthritis is one of several autoimmune disorders in which cellular defense mechanisms identify the body's own tissues as foreign and seek to destroy them. Other autoimmune disorders include such ailments as Graves' disease, multiple sclerosis and lupus. This research suggests that there could be a common therapeutic strategy for these conditions.
To speak to Dr. Smith, contact David Feuerherd at dfissuesmanagement.
Contact: David Feuerherd
dfissuesmanagement
310-215-0234
Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center (LA BioMed)
среда, 8 июня 2011 г.
GlaxoSmithKlline And Genmab Present Positive Phase II Results With Ofatumumab In Patients With Rheumatoid Arthritis (RA)
GlaxoSmithKline (GSK) and Genmab A/S (CSE: GEN) announced today positive primary efficacy data (evaluated at 24 Weeks) to be presented at EULAR 2007, the Annual European Congress of Rheumatology (abstract number: OPO232) from a Phase II study of ofatumumab (HuMax-CD20®) in patients with rheumatoid arthritis (RA). Ofatumumab is being co-developed under a worldwide agreement between GlaxoSmithKline and Genmab.
A total of 225 patients with active RA who have previously failed one or more disease-modifying anti-rheumatic drugs (DMARDs) were enrolled into this double-blind placebo controlled study to evaluate the safety and efficacy of ofatumumab. Patients within the study were randomized into one of four treatment groups (300 mg, 700 mg or 1000 mg ofatumumab or placebo) and assessed based on their AmericanCollegeof Rheumatology (ACR) and EULAR responses at 24 weeks. Continuation of current stable doses of methotrexate and low dose corticosteroids were permitted.
In the intention-to-treat study population, comprising 224 patients, ACR20 was achieved by 46% of all patients receiving ofatumumab, ACR50 achieved by 24% and ACR70 achieved by 6% of ofatumumab patients compared to 15%, 5% and 0% in the placebo group. Evaluated by dose groups, an ACR20 response was obtained by 41% (p=0.002), 49% (p
A total of 225 patients with active RA who have previously failed one or more disease-modifying anti-rheumatic drugs (DMARDs) were enrolled into this double-blind placebo controlled study to evaluate the safety and efficacy of ofatumumab. Patients within the study were randomized into one of four treatment groups (300 mg, 700 mg or 1000 mg ofatumumab or placebo) and assessed based on their AmericanCollegeof Rheumatology (ACR) and EULAR responses at 24 weeks. Continuation of current stable doses of methotrexate and low dose corticosteroids were permitted.
In the intention-to-treat study population, comprising 224 patients, ACR20 was achieved by 46% of all patients receiving ofatumumab, ACR50 achieved by 24% and ACR70 achieved by 6% of ofatumumab patients compared to 15%, 5% and 0% in the placebo group. Evaluated by dose groups, an ACR20 response was obtained by 41% (p=0.002), 49% (p
вторник, 7 июня 2011 г.
Arthritis Pain, The Brain And The Role Of Emotions
How does the brain process the experience of pain? Thanks to advances in neuroimaging, we now know the answer lies in a network of brain structures called the pain matrix. This matrix contains two parallel systems. The medial pain system processes the emotional aspects of pain, including fear and stress, while the lateral system processes the physical sensations-pain's intensity, location, and duration.
Marked by morning stiffness, joint aches, and flare-ups, the pain of arthritis tends to be acute and recurrent, in contrast to many chronic pain conditions. Arthritis pain therefore makes an ideal model for comparing common clinical pain with experimental pain. Inspired by this observation, researchers at University of Manchester Rheumatic Diseases Centre in the United Kingdom conducted the first study to compare directly the brain areas involved in processing arthritis pain and experimental pain in a group of patients with osteoarthritis (OA). Their results, published in the April 2007 issue of Arthritis & Rheumatism (interscience.wiley/journal/arthritis), shed light on the role of emotions in how patients feel arthritis pain.
The study focused on 12 patients with knee OA-6 women and 6 men, with a mean age of 52 years. All subjects underwent positron emission tomography (PET), to measure and map 18F-fluorodeoxyglucose (FDG) uptake in the brain as an indicator of brain activity. PET scans were performed during three different pain conditions: arthritic knee pain; experimental pain, achieved by heat application; and pain-free. The brain responses to each pain state were then rigorously examined and statistically evaluated and compared for significant differences.
In all OA subjects, both pain conditions activated the entire pain matrix. However, during arthritic pain, activity was increased within the medial pain system of the brain, including most of the cingulate cortex, the thalamus, and the amygdala. This suggests that, for these patients, arthritis pain has more emotional impact-and perhaps stronger associations with fear and distress-than experimental pain. Arthritis pain also prompted heightened activation of the prefrontal cortex and the inferior posterior parietal cortex, areas of the brain instrumental in the supervision of attention. Their activation while suffering arthritis pain may reflect the patients' concentration on coping strategies.
"The present study demonstrates the importance of the medial pain system during the experience of arthritic pain and suggests that it is a likely target for both pharmacologic and nonpharmacologic interventions," notes its leading author, Prof. A.K.P. Jones. "Considering the recent concerns about the long-term safety of cyclo-oxygenase inhibitors, we hope that our current findings will stimulate partnerships between academia and the pharmacological industry to develop a new class of analgesics for arthritic pain that specifically target the medial pain system."
As Prof. Jones acknowledges, the study's main limitation is its small number of subjects. Larger studies of the relationship between arthritis pain and the medial pain system are critical, particularly for exploring the effect of variables from depression and anxiety to guided imagery, meditation, and other mind-based pain management techniques. "Researchers should be moving toward more naturalistic studies in patients," Prof. Jones suggests, "in order to fully understand the perception of different types of clinical pain."
Article: "Arthritic Pain Is Processed in Brain Areas Concern With Emotions and Fear," B. Kulkarni, D.E. Bentley, R. Elliott, P.J. Julyan, E. Boger, A. Watson, Y. Boyle, W. El-Deredy, and A.K.P. Jones, Arthritis & Rheumatism, April 2007; (DOI: 10.1002/art.22460).
Contact: Amy Molnar
John Wiley & Sons, Inc.
Marked by morning stiffness, joint aches, and flare-ups, the pain of arthritis tends to be acute and recurrent, in contrast to many chronic pain conditions. Arthritis pain therefore makes an ideal model for comparing common clinical pain with experimental pain. Inspired by this observation, researchers at University of Manchester Rheumatic Diseases Centre in the United Kingdom conducted the first study to compare directly the brain areas involved in processing arthritis pain and experimental pain in a group of patients with osteoarthritis (OA). Their results, published in the April 2007 issue of Arthritis & Rheumatism (interscience.wiley/journal/arthritis), shed light on the role of emotions in how patients feel arthritis pain.
The study focused on 12 patients with knee OA-6 women and 6 men, with a mean age of 52 years. All subjects underwent positron emission tomography (PET), to measure and map 18F-fluorodeoxyglucose (FDG) uptake in the brain as an indicator of brain activity. PET scans were performed during three different pain conditions: arthritic knee pain; experimental pain, achieved by heat application; and pain-free. The brain responses to each pain state were then rigorously examined and statistically evaluated and compared for significant differences.
In all OA subjects, both pain conditions activated the entire pain matrix. However, during arthritic pain, activity was increased within the medial pain system of the brain, including most of the cingulate cortex, the thalamus, and the amygdala. This suggests that, for these patients, arthritis pain has more emotional impact-and perhaps stronger associations with fear and distress-than experimental pain. Arthritis pain also prompted heightened activation of the prefrontal cortex and the inferior posterior parietal cortex, areas of the brain instrumental in the supervision of attention. Their activation while suffering arthritis pain may reflect the patients' concentration on coping strategies.
"The present study demonstrates the importance of the medial pain system during the experience of arthritic pain and suggests that it is a likely target for both pharmacologic and nonpharmacologic interventions," notes its leading author, Prof. A.K.P. Jones. "Considering the recent concerns about the long-term safety of cyclo-oxygenase inhibitors, we hope that our current findings will stimulate partnerships between academia and the pharmacological industry to develop a new class of analgesics for arthritic pain that specifically target the medial pain system."
As Prof. Jones acknowledges, the study's main limitation is its small number of subjects. Larger studies of the relationship between arthritis pain and the medial pain system are critical, particularly for exploring the effect of variables from depression and anxiety to guided imagery, meditation, and other mind-based pain management techniques. "Researchers should be moving toward more naturalistic studies in patients," Prof. Jones suggests, "in order to fully understand the perception of different types of clinical pain."
Article: "Arthritic Pain Is Processed in Brain Areas Concern With Emotions and Fear," B. Kulkarni, D.E. Bentley, R. Elliott, P.J. Julyan, E. Boger, A. Watson, Y. Boyle, W. El-Deredy, and A.K.P. Jones, Arthritis & Rheumatism, April 2007; (DOI: 10.1002/art.22460).
Contact: Amy Molnar
John Wiley & Sons, Inc.
понедельник, 6 июня 2011 г.
Link Between Chronic Inflammation And Atherosclerosis Studied
Rheumatoid arthritis, lupus, and other inflammatory rheumatic diseases are associated with a high rate of death from heart disease. One explanation is a greater susceptibility to atherosclerosis. Although atherosclerosis is linked to inflammation in healthy individuals as well, the mechanism of inflammation and the reason for accelerated atherosclerosis in patients with inflammatory rheumatic disease remain unclear. Does atherosclerosis result from systemic inflammation, a hallmark of these rheumatic diseases, or from local inflammation of vessels?
To shed light on the link between chronic inflammation and atherosclerosis, a team of researchers in Norway and the United States, affiliated with the Cleveland Clinic Foundation and Brigham and Women's Hospital in Boston, focused on the aortas of recent recipients of coronary artery bypass graft (CABG) surgery, comparing biopsy specimens from patients with inflammatory rheumatic disease to those from patients without it. Their study, presented in the June 2007 issue of Arthritis & Rheumatism (interscience.wiley/journal/arthritis), affirms inflammatory rheumatic disease and smoking as independent predictors of vessel wall inflammation. The vascular inflammation might be a factor that promotes atherosclerosis and the formation of aneurysms.
Aortic samples were obtained during CABG surgery, performed at two cardiac centers in Norway, from 66 patients with inflammatory rheumatic disease and 51 control patients. The inflammatory rheumatic disease group included patients with rheumatoid arthritis, psoriatic arthritis, lupus, ankylosing spondylitis, polymyalgia and other diseases. Age, body mass index, family history of heart disease, and other traditional cardiovascular risk factors were similar in both groups. All specimens were evaluated, by light microscope, for evidence of chronic inflammatory cell infiltration in the aortic wall. This was achieved by counting and measuring the mononuclear cell infiltrates (MCI) in the aorta, with particular attention to the adventitia, the deepest layer of vascular tissue. Using statistical analysis, the relationship between these inflammatory infiltrates and established lifestyle risk factors for heart disease was also assessed.
In the adventitia, MCIs occurred more frequently in patients with inflammatory rheumatic disease -- 47 percent of this group, compared with 20 percent of the control group. Along with greater prevalence, these inflammatory cells were larger in size. In the middle layer of the vessel wall (the media), MCIs were detected only in patients with inflammatory rheumatic disease. What's more, MCIs were observed in 6 of 7 patients with a history of aortic aneurysm. In addition to inflammatory rheumatic disease, current smoking was independently associated with more pronounced chronic inflammatory infiltration in the inner adventitia.
"The opportunities for detecting aortic inflammation are limited," acknowledges the study's spokesperson, Ivana Hollan, M.D. "Our method of tissue examination allows the condition to be diagnosed in patients undergoing CABG surgery without increasing the preoperative risk."
Despite the limitations of its small sample size, this groundbreaking study of aortic inflammation in patients with inflammatory rheumatic disease indicates the need for further investigation into an inflammatory process that may increase vulnerability to dying from a heart attack or aneurysm.
Article: "Inflammatory Rheumatic Disease and Smoking Predict Aortic Inflammation: A Controlled Study of Biopsy Specimens Obtained at Coronary Artery Surgery," Ivana Hollan, Helge Scott, Kjell Saatvedt, Richard Prayson, Knut Mikkelsen, Hans C. Nossent, Ingjerd Lien Kvelstad, Matthew H. Liang, and 'wystein T. Forre, Arthritis & Rheumatism, June 2007; (DOI: 10.1002/art.22690).
Contact: Amy Molnar
John Wiley & Sons, Inc.
To shed light on the link between chronic inflammation and atherosclerosis, a team of researchers in Norway and the United States, affiliated with the Cleveland Clinic Foundation and Brigham and Women's Hospital in Boston, focused on the aortas of recent recipients of coronary artery bypass graft (CABG) surgery, comparing biopsy specimens from patients with inflammatory rheumatic disease to those from patients without it. Their study, presented in the June 2007 issue of Arthritis & Rheumatism (interscience.wiley/journal/arthritis), affirms inflammatory rheumatic disease and smoking as independent predictors of vessel wall inflammation. The vascular inflammation might be a factor that promotes atherosclerosis and the formation of aneurysms.
Aortic samples were obtained during CABG surgery, performed at two cardiac centers in Norway, from 66 patients with inflammatory rheumatic disease and 51 control patients. The inflammatory rheumatic disease group included patients with rheumatoid arthritis, psoriatic arthritis, lupus, ankylosing spondylitis, polymyalgia and other diseases. Age, body mass index, family history of heart disease, and other traditional cardiovascular risk factors were similar in both groups. All specimens were evaluated, by light microscope, for evidence of chronic inflammatory cell infiltration in the aortic wall. This was achieved by counting and measuring the mononuclear cell infiltrates (MCI) in the aorta, with particular attention to the adventitia, the deepest layer of vascular tissue. Using statistical analysis, the relationship between these inflammatory infiltrates and established lifestyle risk factors for heart disease was also assessed.
In the adventitia, MCIs occurred more frequently in patients with inflammatory rheumatic disease -- 47 percent of this group, compared with 20 percent of the control group. Along with greater prevalence, these inflammatory cells were larger in size. In the middle layer of the vessel wall (the media), MCIs were detected only in patients with inflammatory rheumatic disease. What's more, MCIs were observed in 6 of 7 patients with a history of aortic aneurysm. In addition to inflammatory rheumatic disease, current smoking was independently associated with more pronounced chronic inflammatory infiltration in the inner adventitia.
"The opportunities for detecting aortic inflammation are limited," acknowledges the study's spokesperson, Ivana Hollan, M.D. "Our method of tissue examination allows the condition to be diagnosed in patients undergoing CABG surgery without increasing the preoperative risk."
Despite the limitations of its small sample size, this groundbreaking study of aortic inflammation in patients with inflammatory rheumatic disease indicates the need for further investigation into an inflammatory process that may increase vulnerability to dying from a heart attack or aneurysm.
Article: "Inflammatory Rheumatic Disease and Smoking Predict Aortic Inflammation: A Controlled Study of Biopsy Specimens Obtained at Coronary Artery Surgery," Ivana Hollan, Helge Scott, Kjell Saatvedt, Richard Prayson, Knut Mikkelsen, Hans C. Nossent, Ingjerd Lien Kvelstad, Matthew H. Liang, and 'wystein T. Forre, Arthritis & Rheumatism, June 2007; (DOI: 10.1002/art.22690).
Contact: Amy Molnar
John Wiley & Sons, Inc.
воскресенье, 5 июня 2011 г.
Combining Celebrex With Low-Dose Aspirin May Reduce Protection From Heart Attack And Stroke, Study Suggests
Millions of Americans take Celebrex for arthritis or other pain. Many, if they are middle-aged or older, also take a low-dose aspirin tablet daily to reduce the risk of heart attack and stroke. Yet they may be getting little protection, because Celebrex keeps the aspirin from doing its job effectively, a new study suggests.
In laboratory studies, University of Michigan researchers found that several coxibs, the drug class to which Celebrex belongs, interfere with aspirin's ability to discourage blood clots, if the aspirin is taken in low doses. Celebrex, also known as celecoxib, is the only coxib currently on the market. The results appear online in the Proceedings of the National Academy of Sciences.
Doctors frequently advise daily low-dose aspirin (81 mg) for patients who have heart conditions, notably a serious form of angina known as unstable angina, or for patients who are at risk of second heart attacks. Aspirin is well-known for its ability to discourage formation of blood clots that can lead to heart attack and stroke. In addition, arthritis patients who take Celebrex regularly are often put on low-dose aspirin because this is thought to counteract Celebrex's own potential clot-promoting effect.
"There are many people who take low-dose aspirin, perhaps as many as half of men over 50. If they are also prescribed Celebrex for arthritis or other pain, our results suggest that the Celebrex will probably interfere with the aspirin's action," says William L. Smith, Ph.D., the study's senior author, Minor J. Coon Professor of Biological Chemistry and chair of the biochemistry department at the U-M Medical School.
"The greatest risk is having people take Celebrex who are taking aspirin for cardiovascular problems that are known to be mitigated by aspirin, including patients with unstable angina or those at risk for a second heart attack," he says. In unstable angina, small clots form in arteries and interfere with blood flow.
Previous studies of healthy subjects found no ill effect on blood clotting when Celebrex was combined with aspirin at higher doses, specifically a daily "regular" aspirin tablet (324 mg), Smith notes.
So it may be that a higher aspirin dose, or spreading out the time between taking low-dose aspirin and Celebrex, will allow aspirin to be effective. Aspirin's undesirable effects on the gastrointestinal tract at higher doses when taken long-term would have to be taken into account.
First, though, the effect seen in the U-M study needs to be replicated in studies of low-dose aspirin and Celebrex in people, perhaps in older patients who have conditions such as rheumatoid arthritis, says Smith. If the effect holds true in people, it will be important to determine if a balance in dose and/or dose regimens can be found so that aspirin and Celebrex can both be effective.
Research details
The researchers used biochemical measurements and X-ray crystallography to discover that celecoxib binds to COX-1, an enzyme that promotes clotting, and slows aspirin's COX-1-blocking action. In animal studies, the researchers found more clumping of platelets - the initial stage of clotting - in blood from animals given Celebrex and low-dose aspirin than in animals given only low-dose aspirin.
Background
Celebrex is one member of a class of drugs known as coxibs or COX-2 inhibitors, developed to selectively block the action of pain-causing enzymes while minimizing side effects such as gastrointestinal problems. Celebrex is the most widely prescribed COX-2 inhibitor in the United States.
More than half of older patients taking COX-2 inhibitors long-term were also taking aspirin to protect against heart disease, according to a 2004 study in the Archives of Internal Medicine.
Additional authors: Gilad Rimon, U-M and Ben-Gurion University of the Negev, Israel, first author; Ranjinder S. Sidhua, D. Adam Lauver, Jullia Y. Lee, Narayan P. Sharma, Chong Yuan, Ryan A. Frieler, Raymond C. Trievel and Benedict R. Lucchesi, all at U-M.
Funding: National Institutes of Health, Heart and Stroke Foundation of Canada
Journal citation: Proceedings of the National Academy of Sciences, advance publication online Dec. 1, pnas/cgi/doi/10.1073/pnas.0909765106
Source: Anne Rueter
University of Michigan Health System
In laboratory studies, University of Michigan researchers found that several coxibs, the drug class to which Celebrex belongs, interfere with aspirin's ability to discourage blood clots, if the aspirin is taken in low doses. Celebrex, also known as celecoxib, is the only coxib currently on the market. The results appear online in the Proceedings of the National Academy of Sciences.
Doctors frequently advise daily low-dose aspirin (81 mg) for patients who have heart conditions, notably a serious form of angina known as unstable angina, or for patients who are at risk of second heart attacks. Aspirin is well-known for its ability to discourage formation of blood clots that can lead to heart attack and stroke. In addition, arthritis patients who take Celebrex regularly are often put on low-dose aspirin because this is thought to counteract Celebrex's own potential clot-promoting effect.
"There are many people who take low-dose aspirin, perhaps as many as half of men over 50. If they are also prescribed Celebrex for arthritis or other pain, our results suggest that the Celebrex will probably interfere with the aspirin's action," says William L. Smith, Ph.D., the study's senior author, Minor J. Coon Professor of Biological Chemistry and chair of the biochemistry department at the U-M Medical School.
"The greatest risk is having people take Celebrex who are taking aspirin for cardiovascular problems that are known to be mitigated by aspirin, including patients with unstable angina or those at risk for a second heart attack," he says. In unstable angina, small clots form in arteries and interfere with blood flow.
Previous studies of healthy subjects found no ill effect on blood clotting when Celebrex was combined with aspirin at higher doses, specifically a daily "regular" aspirin tablet (324 mg), Smith notes.
So it may be that a higher aspirin dose, or spreading out the time between taking low-dose aspirin and Celebrex, will allow aspirin to be effective. Aspirin's undesirable effects on the gastrointestinal tract at higher doses when taken long-term would have to be taken into account.
First, though, the effect seen in the U-M study needs to be replicated in studies of low-dose aspirin and Celebrex in people, perhaps in older patients who have conditions such as rheumatoid arthritis, says Smith. If the effect holds true in people, it will be important to determine if a balance in dose and/or dose regimens can be found so that aspirin and Celebrex can both be effective.
Research details
The researchers used biochemical measurements and X-ray crystallography to discover that celecoxib binds to COX-1, an enzyme that promotes clotting, and slows aspirin's COX-1-blocking action. In animal studies, the researchers found more clumping of platelets - the initial stage of clotting - in blood from animals given Celebrex and low-dose aspirin than in animals given only low-dose aspirin.
Background
Celebrex is one member of a class of drugs known as coxibs or COX-2 inhibitors, developed to selectively block the action of pain-causing enzymes while minimizing side effects such as gastrointestinal problems. Celebrex is the most widely prescribed COX-2 inhibitor in the United States.
More than half of older patients taking COX-2 inhibitors long-term were also taking aspirin to protect against heart disease, according to a 2004 study in the Archives of Internal Medicine.
Additional authors: Gilad Rimon, U-M and Ben-Gurion University of the Negev, Israel, first author; Ranjinder S. Sidhua, D. Adam Lauver, Jullia Y. Lee, Narayan P. Sharma, Chong Yuan, Ryan A. Frieler, Raymond C. Trievel and Benedict R. Lucchesi, all at U-M.
Funding: National Institutes of Health, Heart and Stroke Foundation of Canada
Journal citation: Proceedings of the National Academy of Sciences, advance publication online Dec. 1, pnas/cgi/doi/10.1073/pnas.0909765106
Source: Anne Rueter
University of Michigan Health System
суббота, 4 июня 2011 г.
Novel Way To Remove Iron From Ferritin Discovered By Scientists
A new study led by Children's Hospital Oakland Research Institute senior scientist, Elizabeth Theil, Ph.D., is the first to suggest that a small protein or heptapeptide (seven amino acids wrapped into one unit) could be used to accelerate the removal of iron from ferritin. The results of this study may help scientists develop new medications that dramatically improve the removal of excess iron in patients diagnosed with blood diseases such as B-Thalassemia (Cooley's anemia) or Sickle Cell Disease.
The study appears in this month's issue of the Journal of Biological Chemistry and was conducted by Dr. Theil and her co-authors Xiaofeng S. Liu, postdoctoral fellow at Children's Hospital Oakland Research Institute, Marvin J. Miller, Ph.D. and Leslie D. Patterson, a predoctoral student, both from the University of Notre Dame. The scientists knew that the ferritin protein cage had pores that could open and close. It was also known that chelators (a method to detoxify blood) removed iron faster when the pores were open.
"We wanted to prove a hypothesis that a small protein or peptide could bind to ferritin and could be used to regulate ferritin pores," said Dr. Theil. "Our hypothesis was correct. We proved that when a binding peptide of seven amino acids, a heptapeptide, is coupled with Desferal the rate of removal of iron from ferritin is eight times faster." Desferal is currently used to detoxify the blood of patients with iron overload and is a common therapeutic remedy.
Ferritin is a protein that concentrates iron in its inner core or 'cage'. It plays a critical role in understanding iron overload, which can lead to a variety of symptoms including chronic fatigue, weakness, joint pain and arthritis. If left untreated, iron overload can lead to serious problems, including diabetes, liver and heart disease.
The study's results are based on laboratory tests. The National Institutes of Health (NIH), the Cooley's Anemia Foundation and Children's Hospital & Research Center Oakland provided funding for this research.
Click here for more information on Dr. Theil's research.
Research at Children's Hospital & Research Center Oakland, CA
Research efforts at Children's Hospital & Research Center Oakland are coordinated through Children's Hospital Oakland Research Institute (CHORI). Children's Hospital Oakland is Northern California's only freestanding and independent children's hospital. CHORI's internationally renowned biomedical research facility brings together seven centers of excellence that are devoted to clinical and basic science research to treat and prevent disease. CHORI has approximately 300 staff members and an annual budget of more than $49 million. The National Institutes of Health is CHORI's primary funding source. The institute is a leader in translational research, bringing bench discoveries to bedside applications. These include providing cures for blood diseases, developing new vaccines for infectious diseases and discovering new treatment protocols for previously fatal or debilitating conditions such as cancers, sickle cell disease and thalassemia, diabetes, asthma, HIV/AIDS, pediatric obesity, nutritional deficiencies, birth defects, hemophilia and cystic fibrosis.
Source: Venita Robinson
Children's Hospital & Research Center at Oakland
The study appears in this month's issue of the Journal of Biological Chemistry and was conducted by Dr. Theil and her co-authors Xiaofeng S. Liu, postdoctoral fellow at Children's Hospital Oakland Research Institute, Marvin J. Miller, Ph.D. and Leslie D. Patterson, a predoctoral student, both from the University of Notre Dame. The scientists knew that the ferritin protein cage had pores that could open and close. It was also known that chelators (a method to detoxify blood) removed iron faster when the pores were open.
"We wanted to prove a hypothesis that a small protein or peptide could bind to ferritin and could be used to regulate ferritin pores," said Dr. Theil. "Our hypothesis was correct. We proved that when a binding peptide of seven amino acids, a heptapeptide, is coupled with Desferal the rate of removal of iron from ferritin is eight times faster." Desferal is currently used to detoxify the blood of patients with iron overload and is a common therapeutic remedy.
Ferritin is a protein that concentrates iron in its inner core or 'cage'. It plays a critical role in understanding iron overload, which can lead to a variety of symptoms including chronic fatigue, weakness, joint pain and arthritis. If left untreated, iron overload can lead to serious problems, including diabetes, liver and heart disease.
The study's results are based on laboratory tests. The National Institutes of Health (NIH), the Cooley's Anemia Foundation and Children's Hospital & Research Center Oakland provided funding for this research.
Click here for more information on Dr. Theil's research.
Research at Children's Hospital & Research Center Oakland, CA
Research efforts at Children's Hospital & Research Center Oakland are coordinated through Children's Hospital Oakland Research Institute (CHORI). Children's Hospital Oakland is Northern California's only freestanding and independent children's hospital. CHORI's internationally renowned biomedical research facility brings together seven centers of excellence that are devoted to clinical and basic science research to treat and prevent disease. CHORI has approximately 300 staff members and an annual budget of more than $49 million. The National Institutes of Health is CHORI's primary funding source. The institute is a leader in translational research, bringing bench discoveries to bedside applications. These include providing cures for blood diseases, developing new vaccines for infectious diseases and discovering new treatment protocols for previously fatal or debilitating conditions such as cancers, sickle cell disease and thalassemia, diabetes, asthma, HIV/AIDS, pediatric obesity, nutritional deficiencies, birth defects, hemophilia and cystic fibrosis.
Source: Venita Robinson
Children's Hospital & Research Center at Oakland
пятница, 3 июня 2011 г.
Common Childhood Sports Injury Can Lead To Early Onset Of Arthritis
Seventeen-year-old Claire Anthony lives for sports. Her list of activities includes skiing, basketball, hockey, track and volleyball. But a tear to her anterior cruciate ligament, or ACL, while playing basketball at the age of 14, and one to her other knee two years later during a volleyball game, has slowed her active lifestyle.
But athletes like Anthony who injure their ACL - one of the four major ligaments in the knee - have more to worry about than the long road to recovery and being sidelined for months at a time.
Nearly 70 percent of ACL injuries in these young athletes will lead to an early onset of osteoarthritis, a degenerative arthritis that causes the breakdown of the cartilage in joints that only worsens over time.
"I have a lot of concerns about what's going to happen when I'm older." says Anthony. "I've been told that I will get arthritis very soon in life, and there could be more knee surgeries in the future that would prevent me from playing college sports."
But a new study at the University of Michigan is looking to offer these young athletes hope and relief from degenerative arthritis.
Led by Riann Palmieri, Ph.D., assistant professor in the U-M Division of Kinesiology, and Edward Wojtys, M.D., medical director of MedSport Sports Medicine Program at UMHS, the study will work to identify the earliest signs of degenerative arthritis in young knees, to allow for early medical intervention that would prevent the progression of the disease.
"There's no doubt that the number of ACL injuries have increased, especially among children," says Wojtys, associate professor of orthopaedic surgery at the U-M Medical School. "What's concerning is that by the time those kids are in their late teens or early 20s, they'll be living with osteoarthritis as a result of that ACL injury."
He continues: "If our study can identify the earliest changes in the knee joint among these young athletes, we have the hope to do something to try to prevent the ongoing progress."
The study, funded by National Football League Charities Foundation, will use sophisticated imaging such as MRI and biochemical techniques to look for changes in the knee joints of teens who have suffered ACL injuries.
ACL injuries and arthritis
Each year, 1 out of 3,000 people will suffer from an ACL injury. While the injury is most common among children and teens, young female athletes are at the greatest risk. According to Wojtys, the ACL injury rate for a female college basketball team is near 1 in 40 players.
The ACL, located in the center of the knee joint, prevents the lower leg bone called the tibia from moving forward unexpectedly. It also plays a role in controlling rotation in the knee joint.
When injured, it can completely tear, resulting in a rupture, or partially tear, causing a sprain. An ACL will not heal by itself. It must be surgically reconstructed by using ligaments or tendons from another part of the body to replace the torn ACL. Rehabilitation after surgery is very complex, and it may take four to nine months to get back to regular activities, or 12 months for the knee to feel the way it used to.
"We've all seen the NFL football games where there's a tremendous collision and then someone is carted off field. But in reality, most ACLs are ruptured in non-contact events," explains Wojtys.
ACL injuries are frequently associated with damage to the delicate lining on the surface of bone that does not heal. Osteoarthritis is the result of continued deterioration to the bone surface and cartilage in joints. It is three times more common in women and it is a lifetime disease that progressively worsens.
U-M experts, through this new study, hope to learn whether or not the early stages of this degenerative disease can be prevented through altering the patient's rehabilitation program, limiting certain activities after injury, or changing the timeframe for which a patient can return to playing sports.
Information about studies underway at the U-M Health System is available via the U-M Engage clinical research web site, med.umich/engage
Public Relations & Marketing Communications
2901 Hubbard St., Ste. 2400
Ann Arbor, MI 48109-2435
United States
medicineatmichigan/magazine/
But athletes like Anthony who injure their ACL - one of the four major ligaments in the knee - have more to worry about than the long road to recovery and being sidelined for months at a time.
Nearly 70 percent of ACL injuries in these young athletes will lead to an early onset of osteoarthritis, a degenerative arthritis that causes the breakdown of the cartilage in joints that only worsens over time.
"I have a lot of concerns about what's going to happen when I'm older." says Anthony. "I've been told that I will get arthritis very soon in life, and there could be more knee surgeries in the future that would prevent me from playing college sports."
But a new study at the University of Michigan is looking to offer these young athletes hope and relief from degenerative arthritis.
Led by Riann Palmieri, Ph.D., assistant professor in the U-M Division of Kinesiology, and Edward Wojtys, M.D., medical director of MedSport Sports Medicine Program at UMHS, the study will work to identify the earliest signs of degenerative arthritis in young knees, to allow for early medical intervention that would prevent the progression of the disease.
"There's no doubt that the number of ACL injuries have increased, especially among children," says Wojtys, associate professor of orthopaedic surgery at the U-M Medical School. "What's concerning is that by the time those kids are in their late teens or early 20s, they'll be living with osteoarthritis as a result of that ACL injury."
He continues: "If our study can identify the earliest changes in the knee joint among these young athletes, we have the hope to do something to try to prevent the ongoing progress."
The study, funded by National Football League Charities Foundation, will use sophisticated imaging such as MRI and biochemical techniques to look for changes in the knee joints of teens who have suffered ACL injuries.
ACL injuries and arthritis
Each year, 1 out of 3,000 people will suffer from an ACL injury. While the injury is most common among children and teens, young female athletes are at the greatest risk. According to Wojtys, the ACL injury rate for a female college basketball team is near 1 in 40 players.
The ACL, located in the center of the knee joint, prevents the lower leg bone called the tibia from moving forward unexpectedly. It also plays a role in controlling rotation in the knee joint.
When injured, it can completely tear, resulting in a rupture, or partially tear, causing a sprain. An ACL will not heal by itself. It must be surgically reconstructed by using ligaments or tendons from another part of the body to replace the torn ACL. Rehabilitation after surgery is very complex, and it may take four to nine months to get back to regular activities, or 12 months for the knee to feel the way it used to.
"We've all seen the NFL football games where there's a tremendous collision and then someone is carted off field. But in reality, most ACLs are ruptured in non-contact events," explains Wojtys.
ACL injuries are frequently associated with damage to the delicate lining on the surface of bone that does not heal. Osteoarthritis is the result of continued deterioration to the bone surface and cartilage in joints. It is three times more common in women and it is a lifetime disease that progressively worsens.
U-M experts, through this new study, hope to learn whether or not the early stages of this degenerative disease can be prevented through altering the patient's rehabilitation program, limiting certain activities after injury, or changing the timeframe for which a patient can return to playing sports.
Information about studies underway at the U-M Health System is available via the U-M Engage clinical research web site, med.umich/engage
Public Relations & Marketing Communications
2901 Hubbard St., Ste. 2400
Ann Arbor, MI 48109-2435
United States
medicineatmichigan/magazine/
четверг, 2 июня 2011 г.
Arthritis pain, an effective management plan for doctors
Nearly every clinician is likely to encounter a patient trying to cope with arthritis pain, the effects of which can range from annoying to debilitating. The ingredients of an effective management plan: clearly defined therapeutic goals, individualized treatment and close patient/provider communication, knowledge of all available treatment options, and a willingness to employ a team-based approach.
A ccording to the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), more than 40 million Americans are affected by at least one of the more than 100 forms of arthritis, and many have chronic pain that limits daily activity. By the year 2020, the Centers for Disease Control and Prevention predicts that as many as 60 million people will have some form of the disease.
Arthritis pain can come from a variety of sources, including inflam-mation of the synovial membrane, tendons or ligaments, as well as muscle strain, fatigue, or a combination of these factors. Swelling and damage that has occurred within the joint can also be a factor. "Arthritis pain is something that physicians from all backgrounds are likely to encounter during their clinical experience," explains Jon D. Levine, MD. "It is not limited to physicians who specialize in rheumatic diseases or pain. Arthritis pain cases are seen every day in the primary care, ortho-pedic, and neurology settings, as well as in the emergency department."
"Some patients with arthritis may have weakness, be unable to run, or have other problems that are associated with the disease, but they will finally seek attention when the pain sets in," says Dr. Levine. "When these patients present, we need to establish their desired outcome and assess the potential side effects and reactions to different treatment options. We also need to consider the patient's current medication use and if the individual has other medical conditions. Age, gender, and lifestyle are also important considerations. Depending on the patient, different treatment options may have varying implications."
Physicians should develop a management plan designed to minimize specific pain and improve joint functioning, according to Dr. Levine. "Each individual has a different threshold and tolerance for pain that is often affected by both physical and emotional factors. They may also have depression, anxiety, and hypersensitivity at the affected sites due to inflam-mation and tissue injury. These comorbidities can make it difficult for physicians to determine optimal treatments for patients with arthritis pain. It is important to determine the clinical source of our patient's pain rather than just treat the condition and expect the pain to subside. We need to establish if the pain is inflam-matory, neuro- pathic, or a generalized pain syndrome, and then understand the kinds of features that can cause exacerbation of the pain."
Medications, heat and cold therapy, joint protection, transcutaneous electrical nerve stimulation (TENS), and massage therapy are among the short-term treatments for arthritis pain. Long-term treatments may include medications, weight reduction strategies, and exercise. In some patients, surgery may be necessary to remove inflamed joint tissue, realign the joint, or replace severely damaged joints with artificial ones. In appropriate cases, these surgical procedures can provide pain relief and improved motion in the involved joint.
According to Dr. Levine, some physicians are uncomfortable in managing their patient's pain because there is no single treatment that applies to all patients. "For this reason, we need to learn all we can about the available treatment options and become educated on the best management approaches for the individual rather than using a 'cookie-cutter' approach. Surgery may be a good option for some patients with pain, but others may be better suited to use medications or alter their lifestyle. As physicians, we need to evaluate the treatment options on a case-by-case basis."
CONTINUES.......physweekly
A ccording to the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), more than 40 million Americans are affected by at least one of the more than 100 forms of arthritis, and many have chronic pain that limits daily activity. By the year 2020, the Centers for Disease Control and Prevention predicts that as many as 60 million people will have some form of the disease.
Arthritis pain can come from a variety of sources, including inflam-mation of the synovial membrane, tendons or ligaments, as well as muscle strain, fatigue, or a combination of these factors. Swelling and damage that has occurred within the joint can also be a factor. "Arthritis pain is something that physicians from all backgrounds are likely to encounter during their clinical experience," explains Jon D. Levine, MD. "It is not limited to physicians who specialize in rheumatic diseases or pain. Arthritis pain cases are seen every day in the primary care, ortho-pedic, and neurology settings, as well as in the emergency department."
"Some patients with arthritis may have weakness, be unable to run, or have other problems that are associated with the disease, but they will finally seek attention when the pain sets in," says Dr. Levine. "When these patients present, we need to establish their desired outcome and assess the potential side effects and reactions to different treatment options. We also need to consider the patient's current medication use and if the individual has other medical conditions. Age, gender, and lifestyle are also important considerations. Depending on the patient, different treatment options may have varying implications."
Physicians should develop a management plan designed to minimize specific pain and improve joint functioning, according to Dr. Levine. "Each individual has a different threshold and tolerance for pain that is often affected by both physical and emotional factors. They may also have depression, anxiety, and hypersensitivity at the affected sites due to inflam-mation and tissue injury. These comorbidities can make it difficult for physicians to determine optimal treatments for patients with arthritis pain. It is important to determine the clinical source of our patient's pain rather than just treat the condition and expect the pain to subside. We need to establish if the pain is inflam-matory, neuro- pathic, or a generalized pain syndrome, and then understand the kinds of features that can cause exacerbation of the pain."
Medications, heat and cold therapy, joint protection, transcutaneous electrical nerve stimulation (TENS), and massage therapy are among the short-term treatments for arthritis pain. Long-term treatments may include medications, weight reduction strategies, and exercise. In some patients, surgery may be necessary to remove inflamed joint tissue, realign the joint, or replace severely damaged joints with artificial ones. In appropriate cases, these surgical procedures can provide pain relief and improved motion in the involved joint.
According to Dr. Levine, some physicians are uncomfortable in managing their patient's pain because there is no single treatment that applies to all patients. "For this reason, we need to learn all we can about the available treatment options and become educated on the best management approaches for the individual rather than using a 'cookie-cutter' approach. Surgery may be a good option for some patients with pain, but others may be better suited to use medications or alter their lifestyle. As physicians, we need to evaluate the treatment options on a case-by-case basis."
CONTINUES.......physweekly
среда, 1 июня 2011 г.
European Medicines Agency Review Concludes Positive Benefit-risk Balance For Non-selective NSAIDs
The European Medicines Agency has concluded that the benefit-risk balance for non-selective non-steroidal anti-inflammatory drugs (NSAIDs) remains favourable. This conclusion was drawn following a review announced in September 2006 of new thrombotic cardiovascular safety data.
The Agency's Committee for Medicinal Products for Human Use (CHMP), based on currently available information, concluded that:
-- Non-selective NSAIDs are important treatments for arthritis and other painful conditions.
-- It cannot be excluded that non-selective NSAIDs may be associated with a small increase in the absolute risk for thrombotic events, especially when used at high doses for long-term treatment.
-- The overall benefit-risk balance for non-selective NSAIDs remains favourable when used in accordance with the product information, namely on the basis of the overall safety profile of the respective non-selective NSAID, and taking into account the patient's individual risk factors (e.g. gastrointestinal, cardiovascular and renal).
These conclusions are without prejudice to the outcome of the ongoing Article 31 referral procedure for piroxicam, in which the benefit-risk balance is currently being assessed.
Non-selective NSAIDs have been closely monitored by the Agency since initial recommendations were made in October 2005. This latest review is based on newly-available data and analyses on cardiovascular safety stemming from clinical and epidemiological studies which signal a potentially increased thrombotic risk (such as heart attack or stroke) for non-selective NSAIDs, especially when used at high doses and in long-term treatment. Previous reviews of the safety of non-selective NSAIDs and COX-2 inhibitors have also been taken into account.
The Committee confirmed its previous advice for doctors and patients to continue to use the lowest effective dose for the shortest possible duration to control symptoms.
As for all medicinal products marketed in the European Union, non-selective NSAIDs are being continuously monitored and appropriate actions will be taken if any concerns arise.
-- The procedure was initiated in accordance with Article 5(3) of Regulation (EC) No 726/2004. The CHMP opinion for this procedure can be found here emea.europa.eu/htms/human/opiniongen/nsaids06.htm. The assessment report will be published on the EMEA website shortly.
-- A question and answer document on the review of non-selective NSAIDs can be found here emea.europa.eu/pdfs/human/opiniongen/nsaidsq&a.pdf.
-- The press releases following the October 2005 review of non-selective NSAIDs can be found here emea.europa.eu/pdfs/human/press/pr/29896405en.pdf and from September 2006 can be found here emea.europa.eu/pdfs/general/direct/pr/37869506en.pdf.
-- This press release, together with other information about the work of the EMEA, may be found on the EMEA website: emea.europa.eu
The Agency's Committee for Medicinal Products for Human Use (CHMP), based on currently available information, concluded that:
-- Non-selective NSAIDs are important treatments for arthritis and other painful conditions.
-- It cannot be excluded that non-selective NSAIDs may be associated with a small increase in the absolute risk for thrombotic events, especially when used at high doses for long-term treatment.
-- The overall benefit-risk balance for non-selective NSAIDs remains favourable when used in accordance with the product information, namely on the basis of the overall safety profile of the respective non-selective NSAID, and taking into account the patient's individual risk factors (e.g. gastrointestinal, cardiovascular and renal).
These conclusions are without prejudice to the outcome of the ongoing Article 31 referral procedure for piroxicam, in which the benefit-risk balance is currently being assessed.
Non-selective NSAIDs have been closely monitored by the Agency since initial recommendations were made in October 2005. This latest review is based on newly-available data and analyses on cardiovascular safety stemming from clinical and epidemiological studies which signal a potentially increased thrombotic risk (such as heart attack or stroke) for non-selective NSAIDs, especially when used at high doses and in long-term treatment. Previous reviews of the safety of non-selective NSAIDs and COX-2 inhibitors have also been taken into account.
The Committee confirmed its previous advice for doctors and patients to continue to use the lowest effective dose for the shortest possible duration to control symptoms.
As for all medicinal products marketed in the European Union, non-selective NSAIDs are being continuously monitored and appropriate actions will be taken if any concerns arise.
-- The procedure was initiated in accordance with Article 5(3) of Regulation (EC) No 726/2004. The CHMP opinion for this procedure can be found here emea.europa.eu/htms/human/opiniongen/nsaids06.htm. The assessment report will be published on the EMEA website shortly.
-- A question and answer document on the review of non-selective NSAIDs can be found here emea.europa.eu/pdfs/human/opiniongen/nsaidsq&a.pdf.
-- The press releases following the October 2005 review of non-selective NSAIDs can be found here emea.europa.eu/pdfs/human/press/pr/29896405en.pdf and from September 2006 can be found here emea.europa.eu/pdfs/general/direct/pr/37869506en.pdf.
-- This press release, together with other information about the work of the EMEA, may be found on the EMEA website: emea.europa.eu
Подписаться на:
Комментарии (Atom)