Regeneron Pharmaceuticals, Inc. (Nasdaq: REGN) announced the publication of the results of three studies which supported the U.S. Food and Drug Administration (FDA) regulatory submission for ARCALYST® (rilonacept) Injection for Subcutaneous Use for the treatment of Cryopyrin-Associated Periodic Syndromes (CAPS).
Two studies were published in the August 2008 issue of Arthritis and Rheumatism, the flagship publication of the American College of Rheumatology. The first study was the preliminary trial to evaluate the impact of ARCALYST on markers of inflammation, clinical response, and safety and the second was the pivotal efficacy and safety clinical trial of ARCALYST. A third study, conducted to develop and validate a key symptoms assessment scale for CAPS patients and subsequently utilized as the primary endpoint measure in the pivotal clinical study of ARCALYST, was published online in the August 2008 issue of Current Medical Research and Opinion.
ARCALYST, also known as interleukin-1 (IL-1) Trap, is a targeted inhibitor of IL-1, which is the key driver of inflammation in CAPS. ARCALYST is the only therapy approved for patients with CAPS, including Familial Cold Auto-inflammatory Syndrome (FCAS) and Muckle-Wells Syndrome (MWS) in adults and children 12 and older. CAPS represent a group of rare, inherited, auto-inflammatory conditions characterized by life-long, recurrent symptoms of rash, fever/chills, joint pain, eye redness/pain, and fatigue. Intermittent, disruptive exacerbations or flares can be triggered at any time by exposure to cooling temperatures, stress, exercise, or other unknown stimuli. The incidence of CAPS has been reported to be approximately one in 1,000,000 people in the United States.
"The ultimate goal of our work over the last ten years has been to find an effective therapy for Cryopyrin-Associated Periodic Syndromes. We began by characterizing the unusual clinical features and debilitating impact of CAPS and then discovered the underlying genetic basis of the disease. A major concern was whether a pharmaceutical company would expend the significant resources necessary to develop a treatment for a disease that has been diagnosed in only a few hundred patients in the United States," stated Hal Hoffman, M.D., Associate Professor, University of California, San Diego and a leading expert on CAPS. "These publications highlight that scientists, clinicians, and industry can collaborate to efficiently, yet rigorously, develop therapies for rare diseases with significant unmet medical need. As a result of this collaboration, patients with CAPS now have an approved treatment available that can help them to effectively manage their disease."
In the initial, open-label pilot evaluation of ARCALYST® (rilonacept), five patients with the Familial Cold Auto-inflammatory Syndrome (FCAS) sub-type of CAPS experienced a marked improvement in symptoms with a corresponding reduction in markers of inflammation. Based upon these convincing findings, a pivotal clinical program was designed to support a registration filing. In order to develop a basis for measuring symptom severity as reported by CAPS patients in a disease that waxes and wanes from day to day, an observational, non-pharmacologic study was conducted in 48 patients with either FCAS or Muckle-Wells Syndrome (MWS). Systematic evaluation of a series of patient-reported outcomes tools resulted in the development of a validated CAPS symptoms measurement instrument with high internal consistency and reliability.
In the pivotal, randomized, double-blind clinical study, 47 patients with FCAS or MWS were randomized to receive either ARCALYST or placebo for six weeks. Patients treated with ARCALYST experienced an 84 percent statistically significant improvement in overall symptom scores versus baseline, whereas those treated with placebo did not experience a significant improvement in their symptoms (13 percent improvement). Ninety-six percent of patients receiving ARCALYST experienced at least a 30 percent improvement in symptoms during this six-week phase of the study. All patients were subsequently given single-blind ARCALYST for nine weeks. Patients were then re-randomized to either ARCALYST or placebo and evaluated over a subsequent nine-week period. Patients remaining on ARCALYST continued to experience symptom control, whereas those receiving placebo experienced a statistically significant worsening of their CAPS symptoms. The most commonly reported adverse reactions reported with ARCALYST were injection-site reaction and upper respiratory tract infection.
"The development process for ARCALYST for the treatment of CAPS highlights Regeneron's overall approach to drug development - to develop drugs targeted at well-documented mediators of disease, focus clinical development on diseases in which those biologic mediators play a primary underlying role, establish clinical proof of concept, and then strive to conduct efficient, pivotal studies with well-validated clinical endpoints," stated George D. Yancopoulos, M.D., Ph.D., President of Regeneron Research Laboratories. "In this case, recognizing that IL-1 is an active mediator of inflammatory disease, we developed ARCALYST to potently inhibit IL-1 in the bloodstream before it can bind to its receptors. Once it was recognized that the genetic mutation associated with CAPS is associated with IL-1 overproduction, we rapidly initiated a pilot study to determine the clinical impact of IL-1 inhibition with ARCALYST. Based upon the clear-cut responses experienced by the CAPS patients in the pilot study, we then developed a validated instrument to assess the severity of CAPS symptoms over time and introduced that instrument into two randomized, placebo-controlled pivotal study phases."
About Cryopyrin-Associated Periodic Syndromes (CAPS)
Recently, medical researchers have identified and described a group of rare, inherited, auto-inflammatory disorders, known as Cryopyrin-Associated Periodic Syndromes or CAPS. Three related conditions make up the broader disease known as CAPS: Familial Cold Auto-inflammatory Syndrome (FCAS), Muckle-Wells Syndrome (MWS), and Neonatal-Onset Multisystem Inflammatory Disease (NOMID). ARCALYST has not been studied in patients with NOMID.
CAPS are characterized by life-long, recurrent symptoms of rash, fever/chills, joint pain, eye redness/pain, and fatigue. Intermittent, disruptive exacerbations or flares can be triggered at any time by exposure to cooling temperatures, stress, exercise, or other unknown stimuli.
CAPS are generally caused by autosomal-dominant mutations (changes) in the NLRP-3 (previously known as CIAS1) gene and resultant alterations in the protein, cryopyrin, which it encodes. Cryopyrin, active in circulating infection-fighting white blood cells, controls the production of a protein called interleukin-1 (IL-1). As part of the body's infection-fighting defense system, IL-1 circulates throughout the body and can trigger inflammatory reactions when it binds to inflammatory cells. Researchers have found that alterations in the cryopyrin protein lead to over-production of IL-1, resulting in an inflammatory response and the symptoms of CAPS. Most, but not all, patients with CAPS have the NLRP-3 gene mutation.
Important Information About ARCALYST® (rilonacept)
ARCALYST is indicated for the treatment of Cryopyrin-Associated Periodic Syndromes (CAPS), including Familial Cold Auto-inflammatory Syndrome (FCAS) and Muckle-Wells Syndrome (MWS) in adults and children 12 and older. IL-1 blockade may interfere with immune response to infections. Serious, life-threatening infections have been reported in patients taking ARCALYST. ARCALYST should be discontinued if a patient develops a serious infection. Taking ARCALYST with tumor necrosis factor inhibitors is not recommended because this may increase the risk of serious infections. Treatment with ARCALYST should not be initiated in patients with active or chronic infections. Patients should not receive a live vaccine while taking ARCALYST. It is recommended that patients receive all recommended vaccinations prior to initiation of treatment with ARCALYST. Patients should be monitored for changes in their lipid profiles and provided with medical treatment if warranted. Hypersensitivity reactions associated with ARCALYST administration have been rare. Please see the full Prescribing Information for ARCALYST, available online at regeneron/ARCALYST-fpi.pdf.
About Regeneron Pharmaceuticals, Inc.
Regeneron is a fully integrated biopharmaceutical company that discovers, develops, and commercializes medicines for the treatment of serious medical conditions. In addition to ARCALYST® (rilonacept) Injection for Subcutaneous Use, its first commercialized product, Regeneron has therapeutic candidates in clinical trials for the potential treatment of cancer, eye diseases, and inflammatory diseases, and has preclinical programs in other diseases and disorders. Additional information about Regeneron and recent news releases are available on Regeneron's web site at regeneron.
Forward Looking Statement
This news release discusses historical information and includes forward-looking statements about Regeneron and its products, development programs, finances, and business, all of which involve a number of risks and uncertainties, such as risks associated with preclinical and clinical development of Regeneron's drug candidates, determinations by regulatory and administrative governmental authorities which may delay or restrict Regeneron's ability to continue to develop or commercialize its product and drug candidates, competing drugs that are superior to Regeneron's product and drug candidates, uncertainty of market acceptance of Regeneron's product and drug candidates, unanticipated expenses, the availability and cost of capital, the costs of developing, producing, and selling products, the potential for any collaboration agreement, including Regeneron's agreements with the sanofi-aventis Group and Bayer HealthCare, to be canceled or to terminate without any product success, risks associated with third party intellectual property, and other material risks. A more complete description of these and other material risks can be found in Regeneron's filings with the United States Securities and Exchange Commission (SEC), including its Form 10-K for the year ended December 31, 2007 and Form 10-Q for the quarter ending June 30, 2008. Regeneron does not undertake any obligation to update publicly any forward-looking statement, whether as a result of new information, future events, or otherwise unless required by law.
Biosector 2
воскресенье, 12 июня 2011 г.
суббота, 11 июня 2011 г.
Scientists Implicate Gene In Vitiligo And Other Autoimmune Diseases
In a study appearing in the March 22 New England Journal of Medicine, scientists supported by the National Institutes of Health's National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) have discovered a connection between a specific gene and the inflammatory skin condition vitiligo, as well as a possible host of autoimmune diseases.
Vitiligo is a chronic condition in which melanocytes (the cells that make pigment) in the skin are destroyed. As a result, white patches appear on the skin in different parts of the body. Similar patches also appear on both the mucous membranes (tissues that line the inside of the mouth and nose), and perhaps in the retina (inner layer of the eyeball). The hair that grows on areas affected by vitiligo sometimes turns white.
The researchers began a search for genes involved in vitiligo almost a decade ago with the help of the Vitiligo Society in the United Kingdom. "In the beginning we were looking for multiple family members with vitiligo," says Richard Spritz, M.D., director of the Human Medical Genetics Program at the University of Colorado at Denver and Health Sciences Center and lead investigator for the study. The researchers sent a questionnaire to members of the society, asking them about their own vitiligo and whether other family members were affected. As part of the questionnaire, they also asked about other autoimmune diseases. What they learned was that vitiligo was "very highly associated" with a number of other autoimmune diseases, mostly thyroid disease, but also pernicious anemia, rheumatoid arthritis, psoriasis, lupus, Addison's disease, and adult-onset autoimmune diabetes.
That finding prompted the researchers to study families with multiple affected members and to look for similarities in genes among those who were affected. By searching the genome, they discovered a gene, NALP1, that was key to predisposing people to vitiligo and other autoimmune diseases, particularly autoimmune thyroid disease, says Dr. Spritz. "We know that about 20 percent of people with vitiligo also get autoimmune thyroid disease, and this gene may be involved in mediating both of those," he says.
Dr. Spritz says the implications of this finding are exciting. The identified gene controls part of what is called the innate immune system, which is our body's first defense against infection, he says. "When we are attacked by viruses or bacteria, the innate immune system stimulates the inflammatory pathways and calls the rest of the immune system to action. NALP1 is probably a receptor for bacterial or viral signals. We don't know what these signals are, but now that we know what the gene is, we can use that knowledge to search for the signals that trigger autoimmune disease."
"All autoimmune diseases involve the interaction of multiple genes and environmental triggers," he continues. "You are born with your genes, but you are not born with these diseases. Something happens. We don't know what the triggers are that start these diseases, but if we did, maybe we could avoid them or even block the process. In fact, it may even be possible to actually stop the autoimmune disease," he says.
The most immediate application of this research might be for the disease that began the research: vitiligo. Doctors usually treat vitiligo with ultraviolet (UV) light to stimulate skin repigmentation. Scientists also know that there is one medication available (approved for treating rheumatoid arthritis) that blocks an inflammatory pathway thought to be controlled by NALP1. The possibility of combining a drug with UV light to improve vitiligo treatment is intriguing, and Dr. Spritz is now interested in finding out more about how the medication might affect people with vitiligo.
NIAMS Director Stephen I. Katz, M.D., Ph.D., calls the discovery of the NALP1-autoimmunity connection an important advance in the understanding of autoimmune diseases that collectively affect an estimated 15 million to 25 million Americans. "The more we understand about these diseases, including the genes that predispose to them and the environmental factors that trigger them, the closer we come to better treatments and even preventive measures," he says.
Additional support for this research was provided by the National Institute of Allergy and Infectious Diseases, the National Institute of Diabetes and Digestive and Kidney Diseases, the U.K. Vitiligo Society and the National Vitiligo Foundation.
The mission of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), a part of the Department of Health and Human Services' National Institutes of Health, is to support research into the causes, treatment and prevention of arthritis and musculoskeletal and skin diseases; the training of basic and clinical scientists to carry out this research; and the dissemination of information on research progress in these diseases. For more information about NIAMS, call the information clearinghouse at (301) 495-4484 or (877) 22-NIAMS (free call) or visit the NIAMS Web site at niams.nih/.
The National Institutes of Health (NIH) - The Nation's Medical Research Agency - includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit nih/. Jin Y, et al. NAPL1 in vitiligo-associated multiple autoimmune disease. NEJM 2007;365:10-18.
Contact: Ray Fleming
niams.nih/
NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases
Vitiligo is a chronic condition in which melanocytes (the cells that make pigment) in the skin are destroyed. As a result, white patches appear on the skin in different parts of the body. Similar patches also appear on both the mucous membranes (tissues that line the inside of the mouth and nose), and perhaps in the retina (inner layer of the eyeball). The hair that grows on areas affected by vitiligo sometimes turns white.
The researchers began a search for genes involved in vitiligo almost a decade ago with the help of the Vitiligo Society in the United Kingdom. "In the beginning we were looking for multiple family members with vitiligo," says Richard Spritz, M.D., director of the Human Medical Genetics Program at the University of Colorado at Denver and Health Sciences Center and lead investigator for the study. The researchers sent a questionnaire to members of the society, asking them about their own vitiligo and whether other family members were affected. As part of the questionnaire, they also asked about other autoimmune diseases. What they learned was that vitiligo was "very highly associated" with a number of other autoimmune diseases, mostly thyroid disease, but also pernicious anemia, rheumatoid arthritis, psoriasis, lupus, Addison's disease, and adult-onset autoimmune diabetes.
That finding prompted the researchers to study families with multiple affected members and to look for similarities in genes among those who were affected. By searching the genome, they discovered a gene, NALP1, that was key to predisposing people to vitiligo and other autoimmune diseases, particularly autoimmune thyroid disease, says Dr. Spritz. "We know that about 20 percent of people with vitiligo also get autoimmune thyroid disease, and this gene may be involved in mediating both of those," he says.
Dr. Spritz says the implications of this finding are exciting. The identified gene controls part of what is called the innate immune system, which is our body's first defense against infection, he says. "When we are attacked by viruses or bacteria, the innate immune system stimulates the inflammatory pathways and calls the rest of the immune system to action. NALP1 is probably a receptor for bacterial or viral signals. We don't know what these signals are, but now that we know what the gene is, we can use that knowledge to search for the signals that trigger autoimmune disease."
"All autoimmune diseases involve the interaction of multiple genes and environmental triggers," he continues. "You are born with your genes, but you are not born with these diseases. Something happens. We don't know what the triggers are that start these diseases, but if we did, maybe we could avoid them or even block the process. In fact, it may even be possible to actually stop the autoimmune disease," he says.
The most immediate application of this research might be for the disease that began the research: vitiligo. Doctors usually treat vitiligo with ultraviolet (UV) light to stimulate skin repigmentation. Scientists also know that there is one medication available (approved for treating rheumatoid arthritis) that blocks an inflammatory pathway thought to be controlled by NALP1. The possibility of combining a drug with UV light to improve vitiligo treatment is intriguing, and Dr. Spritz is now interested in finding out more about how the medication might affect people with vitiligo.
NIAMS Director Stephen I. Katz, M.D., Ph.D., calls the discovery of the NALP1-autoimmunity connection an important advance in the understanding of autoimmune diseases that collectively affect an estimated 15 million to 25 million Americans. "The more we understand about these diseases, including the genes that predispose to them and the environmental factors that trigger them, the closer we come to better treatments and even preventive measures," he says.
Additional support for this research was provided by the National Institute of Allergy and Infectious Diseases, the National Institute of Diabetes and Digestive and Kidney Diseases, the U.K. Vitiligo Society and the National Vitiligo Foundation.
The mission of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), a part of the Department of Health and Human Services' National Institutes of Health, is to support research into the causes, treatment and prevention of arthritis and musculoskeletal and skin diseases; the training of basic and clinical scientists to carry out this research; and the dissemination of information on research progress in these diseases. For more information about NIAMS, call the information clearinghouse at (301) 495-4484 or (877) 22-NIAMS (free call) or visit the NIAMS Web site at niams.nih/.
The National Institutes of Health (NIH) - The Nation's Medical Research Agency - includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit nih/. Jin Y, et al. NAPL1 in vitiligo-associated multiple autoimmune disease. NEJM 2007;365:10-18.
Contact: Ray Fleming
niams.nih/
NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases
пятница, 10 июня 2011 г.
Comparison Of Latest Rheumatoid Arthritis Drugs
Findings published in the open access journal BMC Musculoskeletal Disorders shows that the latest class of drugs used to treat rheumatoid arthritis (RA) are better than standard anti-inflammatories.
RA is a chronic, debilitating, inflammatory disease of the joints, which is usually treated with anti-inflammatory drugs such as methotrexate or steroids. However, the discovery that a protein from white blood cells, known as tumour necrosis factor alpha (TNF?±), caused some of the symptoms of RA, led to the development of novel drugs which block TNF?±. This group of drugs, known as anti-TNF?± drugs (which include infliximab, etanercept and adalimumab), are now commonly used to treat RA.
However, there have been no 'head-to-head' comparisons of the new anti-TNF?± drugs in terms of safety or efficacy for the treatment of RA.
Alberto Alonso-Ruiz of the Cruces Hospital in Barakaldo, Vizcaya, Spain and colleagues at the Donostia Hospital and the University of the Basque Country, systematically searched for research on the use of anti-TNF?± drugs in RA patients. They found thirteen clinical trials including over 7000 patients. The researchers then analyzed the trial results, systematically logging patient benefits and side effects for different doses of the three main anti-TNF?± drugs.
Analysis of the combined results of all thirteen trials showed that anti-TNF?± drugs, given at recommended doses, were better than the usual treatments, such as methotrexate, for treating RA. Patients who had previously seen little benefit from methotrexate alone showed a better response with combined anti-TNF?± plus methotrexate therapy.
The team found that all three drugs were very similar in their benefits even at doses higher than those recommended by the drug manufacturer. This class of drugs, while very effective, does have a higher frequency of adverse side-effects. Patients on infliximab were most likely to drop out of a trial because of these side effects. In contrast, patients using etanercept had the lowest withdrawal rate. The researchers point out that this could be because this drug was not reported as being used at higher than recommended dosage in the trials.
"Anti-TNF?± drugs such as infliximab, adalimumab and etanercept all appear to be effective in the treatment of RA" said Alonso-Ruiz. "Performing comparisons of new drugs is vital for measuring safety/efficacy relationships and monitoring adverse side-effects"
1. Tumor necrosis factor drugs in rheumatoid arthritis: systematic review and meta-analysis of efficacy and safety
Alberto Alonso-Ruiz, Jose Ignacio Pijoan, Eukene Ansuategui, Arantxa Urkaregi, Marcelo Calabozo and Antonio Quintana
BMC Musculoskeletal Disorders (in press)
Article available at the journal website: biomedcentral/bmcmusculoskeletdisord/
All articles are available free of charge, according to BioMed Central's open access policy.
2. BMC Musculoskeletal Disorders is an open access journal publishing original peer-reviewed research articles in all aspects of the prevention, diagnosis and management of musculoskeletal and associated disorders, as well as related molecular genetics, pathophysiology, and epidemiology. BMC Musculoskeletal Disorders (ISSN 1471-2474) is indexed/tracked/covered by PubMed, MEDLINE, CAS, Scopus, EMBASE, Thomson Scientific (ISI) and Google Scholar.
3. BioMed Central (biomedcentral/) is an independent online publishing house
committed to providing immediate access without charge to the peer-reviewed biological and medical research it publishes. This commitment is based on the view that open
access to research is essential to the rapid and efficient communication of science.
Source: Charlotte Webber
BioMed Central
RA is a chronic, debilitating, inflammatory disease of the joints, which is usually treated with anti-inflammatory drugs such as methotrexate or steroids. However, the discovery that a protein from white blood cells, known as tumour necrosis factor alpha (TNF?±), caused some of the symptoms of RA, led to the development of novel drugs which block TNF?±. This group of drugs, known as anti-TNF?± drugs (which include infliximab, etanercept and adalimumab), are now commonly used to treat RA.
However, there have been no 'head-to-head' comparisons of the new anti-TNF?± drugs in terms of safety or efficacy for the treatment of RA.
Alberto Alonso-Ruiz of the Cruces Hospital in Barakaldo, Vizcaya, Spain and colleagues at the Donostia Hospital and the University of the Basque Country, systematically searched for research on the use of anti-TNF?± drugs in RA patients. They found thirteen clinical trials including over 7000 patients. The researchers then analyzed the trial results, systematically logging patient benefits and side effects for different doses of the three main anti-TNF?± drugs.
Analysis of the combined results of all thirteen trials showed that anti-TNF?± drugs, given at recommended doses, were better than the usual treatments, such as methotrexate, for treating RA. Patients who had previously seen little benefit from methotrexate alone showed a better response with combined anti-TNF?± plus methotrexate therapy.
The team found that all three drugs were very similar in their benefits even at doses higher than those recommended by the drug manufacturer. This class of drugs, while very effective, does have a higher frequency of adverse side-effects. Patients on infliximab were most likely to drop out of a trial because of these side effects. In contrast, patients using etanercept had the lowest withdrawal rate. The researchers point out that this could be because this drug was not reported as being used at higher than recommended dosage in the trials.
"Anti-TNF?± drugs such as infliximab, adalimumab and etanercept all appear to be effective in the treatment of RA" said Alonso-Ruiz. "Performing comparisons of new drugs is vital for measuring safety/efficacy relationships and monitoring adverse side-effects"
1. Tumor necrosis factor drugs in rheumatoid arthritis: systematic review and meta-analysis of efficacy and safety
Alberto Alonso-Ruiz, Jose Ignacio Pijoan, Eukene Ansuategui, Arantxa Urkaregi, Marcelo Calabozo and Antonio Quintana
BMC Musculoskeletal Disorders (in press)
Article available at the journal website: biomedcentral/bmcmusculoskeletdisord/
All articles are available free of charge, according to BioMed Central's open access policy.
2. BMC Musculoskeletal Disorders is an open access journal publishing original peer-reviewed research articles in all aspects of the prevention, diagnosis and management of musculoskeletal and associated disorders, as well as related molecular genetics, pathophysiology, and epidemiology. BMC Musculoskeletal Disorders (ISSN 1471-2474) is indexed/tracked/covered by PubMed, MEDLINE, CAS, Scopus, EMBASE, Thomson Scientific (ISI) and Google Scholar.
3. BioMed Central (biomedcentral/) is an independent online publishing house
committed to providing immediate access without charge to the peer-reviewed biological and medical research it publishes. This commitment is based on the view that open
access to research is essential to the rapid and efficient communication of science.
Source: Charlotte Webber
BioMed Central
четверг, 9 июня 2011 г.
Disabling gene defuses rheumatoid arthritis in mice
Scientists studying mice have identified a gene that allows immune cells known as neutrophils to protect themselves from
the inflammatory chemicals they secrete.
Researchers at Washington University School of Medicine in St. Louis showed that knocking the gene out in mice prevented the
development of an arthritis-like disorder by making the neutrophils victims of their own damaging secretions.
The newly identified role for the gene, Foxo3a, may open a new window for treating arthritic conditions caused by immune
dysfunction. Currently, most treatments in development for these disorders focus either on preventing wayward immune cells
from attacking the joints or on reducing the ability of these cells to open fire. The new results suggest it may be just as
helpful to let these cells kill themselves and each other.
"We already know a great deal about Foxo3a from studies of its role in some cancers, and hopefully that puts us in a good
position to devise ways to manipulate its activity," says senior author Stanford Peng, M.D., Ph.D., assistant professor of
medicine and of pathology and immunology. "If the human version of this gene functions in a similar fashion, modifying its
activity may be a useful approach for arthritis therapy even when the disease is already well underway."
Peng and colleagues will publish their results in the June issue of Nature Medicine.
Rheumatoid arthritis, the most prevalent autoimmune form of arthritis, afflicts approximately 2.1 million Americans or about
1 percent of the population. Women are two to three times more likely to develop the disorder than men. Symptoms often occur
in episodic bursts and may include morning stiffness, fatigue and joint and muscle pain. In severe cases, rheumatoid
arthritis can damage cartilage, tendons, ligaments and bone, leading to joint deformity and instability.
Rheumatoid arthritis has long been recognized as a condition that involves defensive cells from the body's immune system
mistakenly attacking healthy joint tissues. Scientists once thought the cells that were most active in these attacks were
adaptive immune cells including T cells. Most of these cells are like guided missiles: they get a fix on a specific target,
pursue it and attack it.
"Classically, everyone thought that the T cells somehow recognized something specific in the joint like collagen or some
other protein and attacked it," Peng explains. "In recent years, though, it's become more accepted that rheumatoid arthritis
is also the result of a less specific but still harmful inflammation generated by cells from the other branch of the immune
system, the innate immune system."
Innate immune cells such as neutrophils respond rapidly to invaders and normally comprise the body's frontline defenses
against bacterial infection.
Peng became interested in Foxo3a because of prior studies his research team had conducted on a related gene, Foxj1. Both
genes belong to the forkhead family of genes, which regulates the activity of other genes and has been connected to cancer
and longevity. Last year Peng found that knocking out Foxj1 produced a lupus-like condition in mice.
Foxj1 and Foxo3a are thought to play similar roles in immune T cells. To get a better sense for Foxo3a's activities, Peng's
group created a line of mice where Foxo3a had been disabled and studied the effects this change had on T cells.
As a follow-up, Peng decided to inject the new line of mice with antibodies that normally induce a condition like rheumatoid
arthritis. But the mice remained healthy even after the injections.
"It was a surprise finding," Peng says. "We really didn't expect to see this kind of response."
Further study revealed that neutrophils in the mice were killing themselves through a cellular self-destruct process known as
apoptosis. Damaged or highly stressed cells can pull their own plug in this or a similar manner to prevent themselves from
becoming cancerous.
"It seems that evolution has somehow provided protective mechanisms for innate immune cells when they go into the hazardous
inflammatory environments they create," Peng notes. "They need ways to keep themselves alive, and Foxo3a is one of those
ways."
Peng's group is currently trying to discern more details of Foxo3a's activities in neutrophils, including the pathways the
gene activates to block apoptosis. They will also be looking for drugs that inhibit Foxo3a and testing them in the mice as
potential anti-arthritis drugs.
Jonsson H, Allen P, Peng SL. "Inflammatory arthritis requires Foxo3a to prevent Fas ligand-induced neutrophil apoptosis."
Nature Medicine, June 2005.
Funding from Washington University School of Medicine, the National Institutes of Health, the Arthritis Foundation, and the
Lupus Research Institute supported this research.
Washington University School of Medicine's full-time and volunteer faculty physicians also are the medical staff of
Barnes-Jewish and St. Louis Children's hospitals. The School of Medicine is one of the leading medical research, teaching and
patient care institutions in the nation, currently ranked third in the nation by U.S. News & World Report. Through its
affiliations with Barnes-Jewish and St. Louis Children's hospitals, the School of Medicine is linked to BJC HealthCare.
Contact: Michael C. Purdy
purdymwustl
314-286-0122
Washington University School of Medicine
medinfo.wustl
the inflammatory chemicals they secrete.
Researchers at Washington University School of Medicine in St. Louis showed that knocking the gene out in mice prevented the
development of an arthritis-like disorder by making the neutrophils victims of their own damaging secretions.
The newly identified role for the gene, Foxo3a, may open a new window for treating arthritic conditions caused by immune
dysfunction. Currently, most treatments in development for these disorders focus either on preventing wayward immune cells
from attacking the joints or on reducing the ability of these cells to open fire. The new results suggest it may be just as
helpful to let these cells kill themselves and each other.
"We already know a great deal about Foxo3a from studies of its role in some cancers, and hopefully that puts us in a good
position to devise ways to manipulate its activity," says senior author Stanford Peng, M.D., Ph.D., assistant professor of
medicine and of pathology and immunology. "If the human version of this gene functions in a similar fashion, modifying its
activity may be a useful approach for arthritis therapy even when the disease is already well underway."
Peng and colleagues will publish their results in the June issue of Nature Medicine.
Rheumatoid arthritis, the most prevalent autoimmune form of arthritis, afflicts approximately 2.1 million Americans or about
1 percent of the population. Women are two to three times more likely to develop the disorder than men. Symptoms often occur
in episodic bursts and may include morning stiffness, fatigue and joint and muscle pain. In severe cases, rheumatoid
arthritis can damage cartilage, tendons, ligaments and bone, leading to joint deformity and instability.
Rheumatoid arthritis has long been recognized as a condition that involves defensive cells from the body's immune system
mistakenly attacking healthy joint tissues. Scientists once thought the cells that were most active in these attacks were
adaptive immune cells including T cells. Most of these cells are like guided missiles: they get a fix on a specific target,
pursue it and attack it.
"Classically, everyone thought that the T cells somehow recognized something specific in the joint like collagen or some
other protein and attacked it," Peng explains. "In recent years, though, it's become more accepted that rheumatoid arthritis
is also the result of a less specific but still harmful inflammation generated by cells from the other branch of the immune
system, the innate immune system."
Innate immune cells such as neutrophils respond rapidly to invaders and normally comprise the body's frontline defenses
against bacterial infection.
Peng became interested in Foxo3a because of prior studies his research team had conducted on a related gene, Foxj1. Both
genes belong to the forkhead family of genes, which regulates the activity of other genes and has been connected to cancer
and longevity. Last year Peng found that knocking out Foxj1 produced a lupus-like condition in mice.
Foxj1 and Foxo3a are thought to play similar roles in immune T cells. To get a better sense for Foxo3a's activities, Peng's
group created a line of mice where Foxo3a had been disabled and studied the effects this change had on T cells.
As a follow-up, Peng decided to inject the new line of mice with antibodies that normally induce a condition like rheumatoid
arthritis. But the mice remained healthy even after the injections.
"It was a surprise finding," Peng says. "We really didn't expect to see this kind of response."
Further study revealed that neutrophils in the mice were killing themselves through a cellular self-destruct process known as
apoptosis. Damaged or highly stressed cells can pull their own plug in this or a similar manner to prevent themselves from
becoming cancerous.
"It seems that evolution has somehow provided protective mechanisms for innate immune cells when they go into the hazardous
inflammatory environments they create," Peng notes. "They need ways to keep themselves alive, and Foxo3a is one of those
ways."
Peng's group is currently trying to discern more details of Foxo3a's activities in neutrophils, including the pathways the
gene activates to block apoptosis. They will also be looking for drugs that inhibit Foxo3a and testing them in the mice as
potential anti-arthritis drugs.
Jonsson H, Allen P, Peng SL. "Inflammatory arthritis requires Foxo3a to prevent Fas ligand-induced neutrophil apoptosis."
Nature Medicine, June 2005.
Funding from Washington University School of Medicine, the National Institutes of Health, the Arthritis Foundation, and the
Lupus Research Institute supported this research.
Washington University School of Medicine's full-time and volunteer faculty physicians also are the medical staff of
Barnes-Jewish and St. Louis Children's hospitals. The School of Medicine is one of the leading medical research, teaching and
patient care institutions in the nation, currently ranked third in the nation by U.S. News & World Report. Through its
affiliations with Barnes-Jewish and St. Louis Children's hospitals, the School of Medicine is linked to BJC HealthCare.
Contact: Michael C. Purdy
purdymwustl
314-286-0122
Washington University School of Medicine
medinfo.wustl
среда, 8 июня 2011 г.
Can Psychosocial Stress At Work Put At Risk Of Developing Rheumatoid Arthritis?
A Swedish study published in one of the latest issue of Psychotherapy and Psychosomatics discloses new relationships between stress at work and development of rheumatoid arthritis.
Psychosocial work stress, in terms of high psychological demands, low decision latitude or the combination of these stressors (job strain), is associated with an increased risk of several diseases (e.g. cardiovascular disease), but it has not been studied in relation to rheumatoid arthritis (RA). However, research on the relationship between psychosocial work stress and immunological parameters also suggests a possible association with inflammatory conditions, including RA. In order to investigate whether high psychological job demands, low decision latitude and job strain are associated with the risk of developing RA, a group of Swedish investigators used data from EIRA, a large population-based case-control study with incident cases of RA. The study base comprised the population, aged 18 - 65 years, in middle and southern parts of Sweden during 1996 - 2003. In total, 1,221 cases and 1,454 controls participated.
Psychological job demands and job decision latitude were measured according to questions developed by Karasek and Theorell. Questions were posed about participants' present work situations; both demands and decision latitude were categorized using the quartiles among the controls (each gender separately) as cut-off points. High psychological job demands, as well as high decision latitude, were defined as a score above the upper quartile. Low psychological job demands, as well as low decision latitude, were defined as a score below the lower quartile. Job strain was defined as the combination of high demands and low decision latitude.
The investigators also performed a classification of psychological job demands and decision latitude based on a job exposure matrix (JEM), in order to avoid potential bias due to differential recall between cases and controls. Among the controls, mean scores of demands and decision latitude were calculated for each latest reported occupation (each gender separately) where the number of controls was at least 3. Both cases and controls were then given the mean scores according to their latest reported occupation. Cut-off points of psychological job demands and decision latitude were calculated in the same way as described above. The odds ratios (OR) of developing RA with 95% confidence intervals (CI) were calculated for high compared with low psychological job demands and low compared with high decision latitude. Job strain was compared with relaxed working conditions (low psychological job demands and high decision latitude) and with conditions without job strain. OR were interpreted as relative risks, as the study was population-based, and were adjusted for age, sex, residential area, smoking and social class.
High psychological job demands tended to be associated with a decreased risk of RA, especially in the JEM-derived data (OR = 0.8, 95% CI = 0.6 - 1.0). Low decision latitude was associated with an increased risk of RA (selfreported data: OR = 1.6, 95% CI = 1.2 - 2.2, JEM-derived data: OR = 1.3, 95% CI = 1.0 - 1.7). Self-reported job strain was associated with a 30% higher risk of RA, compared with relaxed working conditions, but the CI was wide and the result was not confirmed by JEM-derived data.
To summarize few methodological considerations, the investigators conclude that the observed association between low decision latitude and risk of developing RA is most likely real, and that the influence of various biases is of limited magnitude. The main new finding of this study was that low decision latitude was associated with an increased risk of developing RA, according to both self-reported and JEM-derived information. Low decision latitude is also the component in the demand-control model that has most consistently been related to risk of cardiovascular disease. Furthermore, some evidence that those with high psychological job demands had a decreased risk of RA was found.
Source: Psychotherapy and Psychosomatics
Psychosocial work stress, in terms of high psychological demands, low decision latitude or the combination of these stressors (job strain), is associated with an increased risk of several diseases (e.g. cardiovascular disease), but it has not been studied in relation to rheumatoid arthritis (RA). However, research on the relationship between psychosocial work stress and immunological parameters also suggests a possible association with inflammatory conditions, including RA. In order to investigate whether high psychological job demands, low decision latitude and job strain are associated with the risk of developing RA, a group of Swedish investigators used data from EIRA, a large population-based case-control study with incident cases of RA. The study base comprised the population, aged 18 - 65 years, in middle and southern parts of Sweden during 1996 - 2003. In total, 1,221 cases and 1,454 controls participated.
Psychological job demands and job decision latitude were measured according to questions developed by Karasek and Theorell. Questions were posed about participants' present work situations; both demands and decision latitude were categorized using the quartiles among the controls (each gender separately) as cut-off points. High psychological job demands, as well as high decision latitude, were defined as a score above the upper quartile. Low psychological job demands, as well as low decision latitude, were defined as a score below the lower quartile. Job strain was defined as the combination of high demands and low decision latitude.
The investigators also performed a classification of psychological job demands and decision latitude based on a job exposure matrix (JEM), in order to avoid potential bias due to differential recall between cases and controls. Among the controls, mean scores of demands and decision latitude were calculated for each latest reported occupation (each gender separately) where the number of controls was at least 3. Both cases and controls were then given the mean scores according to their latest reported occupation. Cut-off points of psychological job demands and decision latitude were calculated in the same way as described above. The odds ratios (OR) of developing RA with 95% confidence intervals (CI) were calculated for high compared with low psychological job demands and low compared with high decision latitude. Job strain was compared with relaxed working conditions (low psychological job demands and high decision latitude) and with conditions without job strain. OR were interpreted as relative risks, as the study was population-based, and were adjusted for age, sex, residential area, smoking and social class.
High psychological job demands tended to be associated with a decreased risk of RA, especially in the JEM-derived data (OR = 0.8, 95% CI = 0.6 - 1.0). Low decision latitude was associated with an increased risk of RA (selfreported data: OR = 1.6, 95% CI = 1.2 - 2.2, JEM-derived data: OR = 1.3, 95% CI = 1.0 - 1.7). Self-reported job strain was associated with a 30% higher risk of RA, compared with relaxed working conditions, but the CI was wide and the result was not confirmed by JEM-derived data.
To summarize few methodological considerations, the investigators conclude that the observed association between low decision latitude and risk of developing RA is most likely real, and that the influence of various biases is of limited magnitude. The main new finding of this study was that low decision latitude was associated with an increased risk of developing RA, according to both self-reported and JEM-derived information. Low decision latitude is also the component in the demand-control model that has most consistently been related to risk of cardiovascular disease. Furthermore, some evidence that those with high psychological job demands had a decreased risk of RA was found.
Source: Psychotherapy and Psychosomatics
вторник, 7 июня 2011 г.
Identification Of Role For Proteins In Children's Muscle Disease Could Open Up New Treatment Options
A study presented by Mrs. Elisabeth Elst today shows for the first time that a protein - heat shock protein 60 (HSP60) - that is present in chronic inflammations, triggers a response by T-cells (a type of white blood cells that plays a part in the body's own immune response) in children with juvenile dermatomyositis (JDM).
The specific response has earlier been observed in juvenile idiopathic arthritis, but to date, little is known about the role of HSP60 in inflammatory myositis. Inflammatory myositis (IM) is the name given to a group of diseases that cause inflammation in the muscles of the body, which is mediated by the immune system of the body. The main symptoms are pain and weakness and can cause patient disability because of damage to the muscles. The main types of IM are dermatomyositis and polymyositis.
For children, the conditions of myositis are complex and are characterized by muscle damage due to an inflammatory process of the blood vessels that lie under the skin and muscles. Some of the symptoms include skin changes around the eyelids and over the knuckles and finger joints, as well as weakness in muscles, mainly affecting the large muscles around the hips and shoulders resulting in increased difficulty with walking, climbing stairs, getting up from the floor and lifting the arms. The children also often become uncharacteristically miserable and fractious and they may complain of tummy pain.
Heat shock proteins (HSP) are a group of proteins whose expression is increased when the cells are exposed to elevated temperatures. Production of high levels of heat shock proteins can also be triggered by exposure to different kinds of environmental stress conditions, such as infection, inflammation, exposure of the cell to toxins (e.g. ethanol, arsenic, and ultraviolet light), or water deprivation.
Mrs. Elst, pediatric immunologist at the University Medical Centre Utrecht, said, "We have shown for the first time that HSP60 plays an active part in the control of the inflammatory process in JDM. Thus, therapy aimed at the expansion of T-cells with regulatory capacities reacting to HSP60 could contribute to disease remission in patients with JDM. This conclusion opens up new perspectives for the understanding and approach for antigens in immunotherapy."
Jim Baxter - Onsite tel: +44 (0) 7900 605652
Jo Spadaccino - Onsite tel: +44 (0) 7773 271930
Mia Gannedahl - Office tel: +44 (0) 20 7331 2325
Abstract number: OP0060
About EULAR
* The European League Against Rheumatism (EULAR) is the organization which represents the patient, health professional and scientific societies of rheumatology of all the European nations.
* The aims of EULAR are to reduce the burden of rheumatic diseases on the individual and society and to improve the treatment, prevention and rehabilitation of musculoskeletal diseases. To this end, EULAR fosters excellence in education and research in the field of rheumatology. It promotes the translation of research advances into daily care and fights for the recognition of the needs of people with musculoskeletal diseases by the governing bodies in Europe.
* Diseases of bones and joints, such as rheumatoid arthritis and osteoarthritis cause disability in 4 - 5 % of the adult population and are predicted to rise as people live longer.
* As new treatments emerge and cellular mechanisms are discovered, the 7th Annual European Congress of Rheumatology in Amsterdam (EULAR 2006) brings together more than 10,000 experts - scientists, clinicians, healthcare workers, pharmaceutical companies and patients - to share their knowledge in a global endeavour to challenge the pain and disability caused by musculo-skeletal disorders.
* To find out more information about the activities of EULAR, visit: eular/.
Contact: Mia Gannedahl
European League Against Rheumatism
The specific response has earlier been observed in juvenile idiopathic arthritis, but to date, little is known about the role of HSP60 in inflammatory myositis. Inflammatory myositis (IM) is the name given to a group of diseases that cause inflammation in the muscles of the body, which is mediated by the immune system of the body. The main symptoms are pain and weakness and can cause patient disability because of damage to the muscles. The main types of IM are dermatomyositis and polymyositis.
For children, the conditions of myositis are complex and are characterized by muscle damage due to an inflammatory process of the blood vessels that lie under the skin and muscles. Some of the symptoms include skin changes around the eyelids and over the knuckles and finger joints, as well as weakness in muscles, mainly affecting the large muscles around the hips and shoulders resulting in increased difficulty with walking, climbing stairs, getting up from the floor and lifting the arms. The children also often become uncharacteristically miserable and fractious and they may complain of tummy pain.
Heat shock proteins (HSP) are a group of proteins whose expression is increased when the cells are exposed to elevated temperatures. Production of high levels of heat shock proteins can also be triggered by exposure to different kinds of environmental stress conditions, such as infection, inflammation, exposure of the cell to toxins (e.g. ethanol, arsenic, and ultraviolet light), or water deprivation.
Mrs. Elst, pediatric immunologist at the University Medical Centre Utrecht, said, "We have shown for the first time that HSP60 plays an active part in the control of the inflammatory process in JDM. Thus, therapy aimed at the expansion of T-cells with regulatory capacities reacting to HSP60 could contribute to disease remission in patients with JDM. This conclusion opens up new perspectives for the understanding and approach for antigens in immunotherapy."
Jim Baxter - Onsite tel: +44 (0) 7900 605652
Jo Spadaccino - Onsite tel: +44 (0) 7773 271930
Mia Gannedahl - Office tel: +44 (0) 20 7331 2325
Abstract number: OP0060
About EULAR
* The European League Against Rheumatism (EULAR) is the organization which represents the patient, health professional and scientific societies of rheumatology of all the European nations.
* The aims of EULAR are to reduce the burden of rheumatic diseases on the individual and society and to improve the treatment, prevention and rehabilitation of musculoskeletal diseases. To this end, EULAR fosters excellence in education and research in the field of rheumatology. It promotes the translation of research advances into daily care and fights for the recognition of the needs of people with musculoskeletal diseases by the governing bodies in Europe.
* Diseases of bones and joints, such as rheumatoid arthritis and osteoarthritis cause disability in 4 - 5 % of the adult population and are predicted to rise as people live longer.
* As new treatments emerge and cellular mechanisms are discovered, the 7th Annual European Congress of Rheumatology in Amsterdam (EULAR 2006) brings together more than 10,000 experts - scientists, clinicians, healthcare workers, pharmaceutical companies and patients - to share their knowledge in a global endeavour to challenge the pain and disability caused by musculo-skeletal disorders.
* To find out more information about the activities of EULAR, visit: eular/.
Contact: Mia Gannedahl
European League Against Rheumatism
понедельник, 6 июня 2011 г.
Abbott Announces HUMIRA® (adalimumab) Approved In Japan For The Treatment Of Rheumatoid Arthritis
Abbott announced that it has received approval from the Japanese Ministry of Health, Labour and Welfare for HUMIRA® (adalimumab) for the treatment of rheumatoid arthritis in patients with inadequate response to conventional therapy. This approval is the first for HUMIRA in Japan, where Abbott co-developed and will co-market HUMIRA with Eisai Co., Ltd. HUMIRA is now approved in 75 countries for rheumatoid arthritis and other autoimmune disease indications.
"The approval of HUMIRA in Japan is a significant milestone for Abbott," said Glenn Warner, vice president, Pharmaceuticals, Japan, Abbott. "This approval is both good news for Japanese patients and a significant step forward for Abbott in Japan."
HUMIRA is expected to become available to patients in Japan in the coming months, following the standard pricing approval process.
"The clinical studies of HUMIRA in Japanese patients demonstrated the efficacy and safety of this medicine," said Prof. Nobuyuki Miyasaka, M.D., Department of Collagen Disease and Rheumatology, Tokyo Medical and Dental University Graduate School of Medicine, who was involved in the development of HUMIRA for the treatment of rheumatoid arthritis in Japan.
Abbott has submitted an application for approval of HUMIRA for plaque psoriasis, and is also developing HUMIRA in Japan for Crohn's disease, ankylosing spondylitis, juvenile rheumatoid arthritis and ulcerative colitis. Eisai is co-developing and will jointly market these indications with Abbott.
More Information About Rheumatoid Arthritis
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint inflammation, joint pain and stiffness, which can lead to long-term joint damage. The joints most commonly affected early in the disease are the smaller joints of the fingers, feet and wrists. The elbows, knees, ankles and hips can also be affected. Although there is no cure for RA, people continue to seek treatments that help alleviate pain and inflammation and slow disease progression.
More information on RA and current treatment options can be found at RA.
Important Safety Information
Globally, prescribing information varies; refer to the individual country product label for complete information.
Serious infections, sepsis, rare cases of tuberculosis (TB), and opportunistic infections, including fatalities, have been reported with the use of TNF antagonists, including HUMIRA. Many of the serious infections have occurred in patients on concomitant immunosuppressive therapy that, in addition to their underlying disease could predispose them to infections. Patients must be monitored closely for infections, including tuberculosis, before, during and after treatment with HUMIRA. Treatment should not be initiated in patients with active infections until infections are controlled. HUMIRA should not be used by patients with active TB or other severe infections such as sepsis and opportunistic infections. Patients who develop new infections while using HUMIRA should be monitored closely. HUMIRA should be discontinued if a patient develops a new serious infection until infections are controlled. Physicians should exercise caution when considering use of HUMIRA in patients with a history of recurring infection or with underlying conditions that may predispose patients to infections.
TNF-blocking agents have been associated with reactivation of hepatitis B (HBV) in patients who are chronic carriers of the virus. Some cases have been fatal. Patients at risk for HBV infection should be evaluated for prior evidence of HBV infection before initiating HUMIRA.
The combinations of HUMIRA and anakinra as well as HUMIRA and abatacept is not recommended.
TNF antagonists, including HUMIRA, have been associated in rare cases with demyelinating disease and serious allergic reactions. Rare reports of pancytopenia including aplastic anemia have been reported with TNF-blocking agents. Adverse events of the haematologic system, including medically significant cytopenia have been infrequently reported with HUMIRA.
More cases of malignancies including lymphoma have been observed among patients receiving a TNF antagonist compared with control patients in clinical trials. The size of the control group and limited duration of the controlled portions of studies precludes the ability to draw firm conclusions. Furthermore, there is an increased background lymphoma risk in rheumatoid arthritis patients with long-standing, highly active, inflammatory disease, which complicates the risk estimation. During the long-term open-label trials with HUMIRA, the overall rate of malignancies was similar to what would be expected for an age-, gender- and race-matched general population. With the current knowledge, a possible risk for the development of lymphomas or other malignancies in patients treated with a TNF antagonist cannot be excluded. All patients, and in particular patients with a medical history of extensive immunosuppressant therapy or psoriasis patients with a history of PUVA treatment, should be examined for the presence of non-melanoma skin cancer prior to and during treatment with HUMIRA.
In clinical studies with another TNF antagonist, a higher rate of serious congestive heart failure (CHF) related adverse events including worsening CHF and new onset CHF have been reported. Cases of worsening CHF have also been reported in patients receiving HUMIRA. Physicians should exercise caution when using HUMIRA in patients who have heart failure and monitor them carefully. HUMIRA should not be used in patients with moderate or severe heart failure.
The most frequently reported adverse event (?‰?1/10 patients) at least possibly causally related to HUMIRA is injection site reaction (including pain, swelling, redness or pruritus). Other common adverse events (?‰?1/100 patients) at least possibly causally related to HUMIRA include lower respiratory infections (including pneumonia, bronchitis), viral infections (including influenza, herpes infections), candidiasis, bacterial infection (including urinary tract infections), upper respiratory infection, dizziness (including vertigo), headache, neurologic sensation disorders (including paraesthesias), cough, nasopharyngeal pain, diarrhea, abdominal pain, stomatitis and mouth ulceration, nausea, hepatic enzymes increased, rash, pruritus, musculoskeletal pain, pyrexia and fatigue (including asthenia and malaise).
About HUMIRA
HUMIRA is the only fully human monoclonal antibody approved for the treatment of rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), Crohn???s disease and plaque psoriasis (Ps) in the United States and Europe. HUMIRA is also approved for the treatment of juvenile idiopathic arthritis (JIA) in the United States, and review for JIA in Europe is ongoing. Clinical trials are underway evaluating the potential of HUMIRA in ulcerative colitis. To date, HUMIRA has been approved in 75 countries and more than 250,000 people worldwide are currently being treated with HUMIRA.
HUMIRA resembles antibodies normally found in the body. It works by blocking tumor necrosis factor alpha (TNF-?±), a protein that, when produced in excess, plays a central role in the inflammatory responses of many immune-mediated diseases.
In the United States, HUMIRA is approved by the FDA for reducing signs and symptoms, inducing major clinical response, inhibiting the progression of structural damage, and improving physical function in adult patients with moderately to severely active rheumatoid arthritis (RA). HUMIRA can be used alone or in combination with methotrexate (MTX) or other disease-modifying anti-rheumatic drugs (DMARDs). HUMIRA is indicated for reducing signs and symptoms of moderately to severely active polyarticular juvenile idiopathic arthritis in patients 4 years of age and older. HUMIRA can be used alone or in combination with MTX. HUMIRA is indicated for reducing the signs and symptoms of active arthritis, inhibiting the progression of structural damage and improving physical function in patients with psoriatic arthritis. HUMIRA can be used alone or in combination with MTX or other DMARDs. HUMIRA is indicted for reducing signs and symptoms in patients with active ankylosing spondylitis. HUMIRA is indicated for reducing the signs and symptoms and inducing and maintaining clinical remission in adults with moderately to severely active Crohn's disease who have had an inadequate response to conventional therapy. HUMIRA is indicated for reducing signs and symptoms and inducing clinical remission in these patients if they have also lost response to or are intolerant to infliximab. HUMIRA is indicated for the treatment of adult patients with moderate to severe chronic plaque psoriasis who are candidates for systemic therapy of phototherapy, and when other systemic therapies are medically less appropriate. HUMIRA should only be administered to patients who will be closely monitored and have regular follow-up visits with a physician.
In Europe, HUMIRA, in combination with MTX, is indicated for the treatment of moderate to severe, active RA in adult patients when the response to DMARDs including MTX has been inadequate, and for the treatment of severe, active and progressive RA in adults not previously treated with MTX. HUMIRA can be given as monotherapy in case of intolerance to MTX or when continued treatment with MTX is inappropriate. HUMIRA has been shown to reduce the rate of progression of joint damage as measured by x-ray and to improve physical function, when given in combination with MTX.
Also in Europe, HUMIRA is indicated for the treatment of active and progressive PsA in adults when the response to previous DMARD therapy has been inadequate and for the treatment of severe, active AS in adults who have had an inadequate response to conventional therapy. HUMIRA is indicated for treatment of severe, active Crohn's disease, in patients who have not responded despite a full and adequate course of therapy with a corticosteroid and/or an immunosuppressant; or who are intolerant to or have medical contraindications for such therapies. For induction treatment, HUMIRA should be given in combination with corticosteroids. HUMIRA can be given as monotherapy in case of intolerance to corticosteroids or when continued treatment with corticosteroids is inappropriate. HUMIRA is indicated for the treatment of moderate-to-severe chronic plaque psoriasis in adult patients who failed to respond to or who have a contraindication to, or are intolerant to other systemic therapy including cyclosporine, methotrexate or PUVA.
Abbott's Commitment to Immunology
Abbott is focused on the discovery and development of innovative treatments for immunologic diseases.
About Abbott
Abbott ( NYSE: ABT) is a global, broad-based health care company devoted to the discovery, development, manufacture and marketing of pharmaceuticals and medical products, including nutritionals, devices and diagnostics. The company employs more than 68,000 people and markets its products in more than 130 countries. Abbott employs 2,100 people in Japan with offices in Tokyo, Osaka, Fukui, and Chiba.
Abbott
abbott
View drug information on Humira.
"The approval of HUMIRA in Japan is a significant milestone for Abbott," said Glenn Warner, vice president, Pharmaceuticals, Japan, Abbott. "This approval is both good news for Japanese patients and a significant step forward for Abbott in Japan."
HUMIRA is expected to become available to patients in Japan in the coming months, following the standard pricing approval process.
"The clinical studies of HUMIRA in Japanese patients demonstrated the efficacy and safety of this medicine," said Prof. Nobuyuki Miyasaka, M.D., Department of Collagen Disease and Rheumatology, Tokyo Medical and Dental University Graduate School of Medicine, who was involved in the development of HUMIRA for the treatment of rheumatoid arthritis in Japan.
Abbott has submitted an application for approval of HUMIRA for plaque psoriasis, and is also developing HUMIRA in Japan for Crohn's disease, ankylosing spondylitis, juvenile rheumatoid arthritis and ulcerative colitis. Eisai is co-developing and will jointly market these indications with Abbott.
More Information About Rheumatoid Arthritis
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint inflammation, joint pain and stiffness, which can lead to long-term joint damage. The joints most commonly affected early in the disease are the smaller joints of the fingers, feet and wrists. The elbows, knees, ankles and hips can also be affected. Although there is no cure for RA, people continue to seek treatments that help alleviate pain and inflammation and slow disease progression.
More information on RA and current treatment options can be found at RA.
Important Safety Information
Globally, prescribing information varies; refer to the individual country product label for complete information.
Serious infections, sepsis, rare cases of tuberculosis (TB), and opportunistic infections, including fatalities, have been reported with the use of TNF antagonists, including HUMIRA. Many of the serious infections have occurred in patients on concomitant immunosuppressive therapy that, in addition to their underlying disease could predispose them to infections. Patients must be monitored closely for infections, including tuberculosis, before, during and after treatment with HUMIRA. Treatment should not be initiated in patients with active infections until infections are controlled. HUMIRA should not be used by patients with active TB or other severe infections such as sepsis and opportunistic infections. Patients who develop new infections while using HUMIRA should be monitored closely. HUMIRA should be discontinued if a patient develops a new serious infection until infections are controlled. Physicians should exercise caution when considering use of HUMIRA in patients with a history of recurring infection or with underlying conditions that may predispose patients to infections.
TNF-blocking agents have been associated with reactivation of hepatitis B (HBV) in patients who are chronic carriers of the virus. Some cases have been fatal. Patients at risk for HBV infection should be evaluated for prior evidence of HBV infection before initiating HUMIRA.
The combinations of HUMIRA and anakinra as well as HUMIRA and abatacept is not recommended.
TNF antagonists, including HUMIRA, have been associated in rare cases with demyelinating disease and serious allergic reactions. Rare reports of pancytopenia including aplastic anemia have been reported with TNF-blocking agents. Adverse events of the haematologic system, including medically significant cytopenia have been infrequently reported with HUMIRA.
More cases of malignancies including lymphoma have been observed among patients receiving a TNF antagonist compared with control patients in clinical trials. The size of the control group and limited duration of the controlled portions of studies precludes the ability to draw firm conclusions. Furthermore, there is an increased background lymphoma risk in rheumatoid arthritis patients with long-standing, highly active, inflammatory disease, which complicates the risk estimation. During the long-term open-label trials with HUMIRA, the overall rate of malignancies was similar to what would be expected for an age-, gender- and race-matched general population. With the current knowledge, a possible risk for the development of lymphomas or other malignancies in patients treated with a TNF antagonist cannot be excluded. All patients, and in particular patients with a medical history of extensive immunosuppressant therapy or psoriasis patients with a history of PUVA treatment, should be examined for the presence of non-melanoma skin cancer prior to and during treatment with HUMIRA.
In clinical studies with another TNF antagonist, a higher rate of serious congestive heart failure (CHF) related adverse events including worsening CHF and new onset CHF have been reported. Cases of worsening CHF have also been reported in patients receiving HUMIRA. Physicians should exercise caution when using HUMIRA in patients who have heart failure and monitor them carefully. HUMIRA should not be used in patients with moderate or severe heart failure.
The most frequently reported adverse event (?‰?1/10 patients) at least possibly causally related to HUMIRA is injection site reaction (including pain, swelling, redness or pruritus). Other common adverse events (?‰?1/100 patients) at least possibly causally related to HUMIRA include lower respiratory infections (including pneumonia, bronchitis), viral infections (including influenza, herpes infections), candidiasis, bacterial infection (including urinary tract infections), upper respiratory infection, dizziness (including vertigo), headache, neurologic sensation disorders (including paraesthesias), cough, nasopharyngeal pain, diarrhea, abdominal pain, stomatitis and mouth ulceration, nausea, hepatic enzymes increased, rash, pruritus, musculoskeletal pain, pyrexia and fatigue (including asthenia and malaise).
About HUMIRA
HUMIRA is the only fully human monoclonal antibody approved for the treatment of rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), Crohn???s disease and plaque psoriasis (Ps) in the United States and Europe. HUMIRA is also approved for the treatment of juvenile idiopathic arthritis (JIA) in the United States, and review for JIA in Europe is ongoing. Clinical trials are underway evaluating the potential of HUMIRA in ulcerative colitis. To date, HUMIRA has been approved in 75 countries and more than 250,000 people worldwide are currently being treated with HUMIRA.
HUMIRA resembles antibodies normally found in the body. It works by blocking tumor necrosis factor alpha (TNF-?±), a protein that, when produced in excess, plays a central role in the inflammatory responses of many immune-mediated diseases.
In the United States, HUMIRA is approved by the FDA for reducing signs and symptoms, inducing major clinical response, inhibiting the progression of structural damage, and improving physical function in adult patients with moderately to severely active rheumatoid arthritis (RA). HUMIRA can be used alone or in combination with methotrexate (MTX) or other disease-modifying anti-rheumatic drugs (DMARDs). HUMIRA is indicated for reducing signs and symptoms of moderately to severely active polyarticular juvenile idiopathic arthritis in patients 4 years of age and older. HUMIRA can be used alone or in combination with MTX. HUMIRA is indicated for reducing the signs and symptoms of active arthritis, inhibiting the progression of structural damage and improving physical function in patients with psoriatic arthritis. HUMIRA can be used alone or in combination with MTX or other DMARDs. HUMIRA is indicted for reducing signs and symptoms in patients with active ankylosing spondylitis. HUMIRA is indicated for reducing the signs and symptoms and inducing and maintaining clinical remission in adults with moderately to severely active Crohn's disease who have had an inadequate response to conventional therapy. HUMIRA is indicated for reducing signs and symptoms and inducing clinical remission in these patients if they have also lost response to or are intolerant to infliximab. HUMIRA is indicated for the treatment of adult patients with moderate to severe chronic plaque psoriasis who are candidates for systemic therapy of phototherapy, and when other systemic therapies are medically less appropriate. HUMIRA should only be administered to patients who will be closely monitored and have regular follow-up visits with a physician.
In Europe, HUMIRA, in combination with MTX, is indicated for the treatment of moderate to severe, active RA in adult patients when the response to DMARDs including MTX has been inadequate, and for the treatment of severe, active and progressive RA in adults not previously treated with MTX. HUMIRA can be given as monotherapy in case of intolerance to MTX or when continued treatment with MTX is inappropriate. HUMIRA has been shown to reduce the rate of progression of joint damage as measured by x-ray and to improve physical function, when given in combination with MTX.
Also in Europe, HUMIRA is indicated for the treatment of active and progressive PsA in adults when the response to previous DMARD therapy has been inadequate and for the treatment of severe, active AS in adults who have had an inadequate response to conventional therapy. HUMIRA is indicated for treatment of severe, active Crohn's disease, in patients who have not responded despite a full and adequate course of therapy with a corticosteroid and/or an immunosuppressant; or who are intolerant to or have medical contraindications for such therapies. For induction treatment, HUMIRA should be given in combination with corticosteroids. HUMIRA can be given as monotherapy in case of intolerance to corticosteroids or when continued treatment with corticosteroids is inappropriate. HUMIRA is indicated for the treatment of moderate-to-severe chronic plaque psoriasis in adult patients who failed to respond to or who have a contraindication to, or are intolerant to other systemic therapy including cyclosporine, methotrexate or PUVA.
Abbott's Commitment to Immunology
Abbott is focused on the discovery and development of innovative treatments for immunologic diseases.
About Abbott
Abbott ( NYSE: ABT) is a global, broad-based health care company devoted to the discovery, development, manufacture and marketing of pharmaceuticals and medical products, including nutritionals, devices and diagnostics. The company employs more than 68,000 people and markets its products in more than 130 countries. Abbott employs 2,100 people in Japan with offices in Tokyo, Osaka, Fukui, and Chiba.
Abbott
abbott
View drug information on Humira.
Подписаться на:
Сообщения (Atom)