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.
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