People in less affluent countries appear to suffer from more severe rheumatoid arthritis (RA) than people in wealthy countries, suggests research published ahead of print in the Annals of the Rheumatic Diseases.
A study of 25 mostly European countries showed that the clinical status of patients with RA was inversely correlated with each country's gross domestic product (GDP).
Dr Tuulikki Sokka from Jyvaskyla Central Hospital in Finland and other members of the Quantitative Standard Monitoring of Patients with RA (QUEST-RA) programme, studied clinical and questionnaire data from 6,004 patients who were seen in usual care at 71 rheumatology clinics in 25 countries, including 18 European countries, between 2005 and April 2008.
All patients were assessed according to a standard protocol to evaluate RA, including a formal medical examination, laboratory measures, and a patient self-report health assessment questionnaire. Data were also gathered on use of disease-modifying anti-rheumatic drugs. Patient data were analysed together with the gross domestic product (GDP) for each country.
They found that patients in low GDP countries had statistically significantly higher disease activity levels in all disease activity measures, despite the fact that all patients had access to a rheumatologist and had received drugs to modify their condition.
Disparities in health, including high mortality rates, are recognised to be associated with low socioeconomic status in many specific diseases in many countries. The burden of chronic diseases is recognised as an important neglected global issue, say the authors, and is heaviest in low and middle-income countries.
This study, said the authors, indicates a need for more medical research in low GDP countries, as most previously published data have been derived from western European and North American nations.
The authors conclude "Public health efforts would appear potentially to be as important as the introduction of new therapies to treat RA.
"The burden of arthritis appears substantially greater in 'low GDP' than in 'high GDP' countries. These findings may alert healthcare professionals and designers of health policy towards improving the clinical status of patients with RA in all countries."
"Disparities in rheumatoid arthritis disease activity according to gross domestic product in 25 countries in the QUEST-RA database."
Ann Rheum Dis 2009; doi 10.1136/ard.2009.109983
Source
Annals of the Rheumatic Diseases
среда, 31 августа 2011 г.
воскресенье, 28 августа 2011 г.
FDA Approves New And Easy Way To Take ENBREL, Once Weekly 50 mg/mL Prefilled Syringe
Amgen Inc (NASDAQ:AMGN) and Wyeth Pharmaceuticals, a division of Wyeth (NYSE:WYE), today announced that the new 50 mg/mL prefilled syringe of Enbrel(R) (etanercept) has been approved by the US Food and Drug Administration (FDA) as the recommended dosing form for treatment in all approved adult indications. The new prefilled syringe, available for patient use in the fourth quarter 2004, will eliminate the need to mix drug prior to injecting and allows most patients receiving ENBREL to take only one injection per week, instead of the two 25 mg injections currently used weekly by patients.
"Since the rheumatoid arthritis approval in 1998, ENBREL has helped thousands of people better manage their disease," said Beth Seidenberg, M.D., chief medical officer and senior vice president of global development, Amgen. "This approval provides physicians with the opportunity to offer their patients an easy-to-use prefilled syringe that delivers the same drug patients and physicians have grown to trust."
The FDA approval was based on a study, which found that the ENBREL 50 mg/mL prefilled syringe was shown to be biologically equivalent to two 25 mg vials. The 25 mg formulation will still be available for juvenile rheumatoid arthritis patients and those that prefer that dosing method.
"This new delivery system can make it easier for patients to receive the proven efficacy and established tolerability of ENBREL," said Joseph Camardo, M.D., senior vice president, global medical affairs, Wyeth Pharmaceuticals. "It may be especially beneficial to people who have rheumatoid arthritis or active psoriatic arthritis, as their hands may be affected by the disabling joint destruction these conditions can cause."
ENBREL is a leading biologic treatment for moderately to severely active rheumatoid arthritis and is the first and only TNF inhibitor approved to treat chronic moderate to severe plaque psoriasis, active psoriatic arthritis, active ankylosing spondylitis (arthritis of the spine) and children with moderately to severely polyarticular-course active juvenile rheumatoid arthritis in patients who have had an inadequate response to one or more disease-modifying antirheumatic drugs (DMARDs).
ABOUT ENBREL
ENBREL is the only fully human TNF receptor approved to reduce signs and symptoms, induce major clinical response, improve physical function, and inhibit the progression of structural damage in patients with moderately to severely active rheumatoid arthritis (RA). ENBREL is also indicated to reduce the signs and symptoms and inhibit the progression of structural damage of active arthritis in patients with psoriatic arthritis. ENBREL is the only biologic therapy approved for first-line treatment of RA patients, and can be used alone or in combination with methotrexate.
ENBREL is also approved to reduce the signs and symptoms of moderately to severely active polyarticular-course juvenile rheumatoid arthritis (JRA) in patients who have had an inadequate response to one or more disease-modifying antirheumatic drugs (DMARDs). It is also the first biologic approved to treat the signs and symptoms in patients with active ankylosing spondylitis (AS). ENBREL is indicated for the treatment of adult patients (18 years or older) with chronic moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy.
ENBREL has been used by more than 250,000 patients worldwide across indications.
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 that are involved in the inflammatory process of RA, JRA, psoriasis, psoriatic arthritis and AS. The binding of ENBREL to TNF renders the bound TNF biologically inactive, resulting in significant reduction in inflammatory activity.
Since the product was first introduced, the following have been reported in patients using ENBREL:
-- Serious Infections
-- Many occurred in people prone to infection, such as those
with advanced or poorly controlled diabetes
-- Some serious infections were fatal
-- Rare cases of tuberculosis
-- What to do/Not to do
-- Do not start ENBREL if you have an infection or are allergic to ENBREL or its components.
-- Tell your doctor if you are prone to infection.
-- Stop ENBREL if a serious infection occurs.
-- Contact your doctor if you have questions about ENBREL or develop an infection.
-- Tell your doctor if you have ever been treated for heart failure.
-- Serious nervous system disorders such as multiple sclerosis, seizures, or inflammation of the nerves of the eyes
-- Tell your doctor if you have ever had any of these disorders or if you develop them after starting ENBREL.
-- Rare reports of serious blood disorders (some fatal)
-- Contact your doctor immediately if you develop symptoms such as persistent fever, bruising, bleeding, or paleness.
-- 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 and psoriasis 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.
-- ENBREL can also cause injection site reactions.
-- In a medical study of patients with JRA, infections, headaches, abdominal pain, vomiting, and nausea occurred more frequently than in adults.
-- The kinds of infections reported were generally mild and similar to those usually seen in children.
-- Other serious adverse reactions were reported rarely, including serious infections (2 percent) and depression/personality disorder (1 percent).
Amgen and Wyeth Pharmaceuticals, a division of Wyeth, market ENBREL in North America. Wyeth markets ENBREL outside of North America. Immunex Corporation, a wholly owned subsidiary of Amgen, manufactures ENBREL. Additional information about ENBREL, including full Prescribing Information, can be found on the Web site sponsored by the companies at enbrel or by calling toll free 888-4ENBREL (888-436-2735).
Amgen is a global biotechnology company that discovers, develops, manufactures and markets important human therapeutics based on advances in cellular and molecular biology. Wyeth Pharmaceuticals, a division of Wyeth, has leading products in the areas of women's health care, cardiovascular disease, central nervous system, inflammation, transplantation, hemophilia, oncology, vaccines and nutritional products. Wyeth is one of the world's largest research-driven pharmaceutical and health care products companies. It is a leader in the discovery, development, manufacturing, and marketing of pharmaceuticals, vaccines, biotechnology products and nonprescription medicines that improve the quality of life for people worldwide. The Company's major divisions include Wyeth Pharmaceuticals, Wyeth Consumer Healthcare, and Fort Dodge Animal Health.
This news release contains forward-looking statements that involve significant risks and uncertainties, including those discussed below and others that can be found in Amgen's Form 10-K for the year ended December 31, 2003, and in Amgen's periodic reports on Form 10-Q and Form 8-K. Amgen is providing this information as of the date of this news release and does not undertake any obligation to update any forward-looking statements contained in this document as a result of new information, future events or otherwise.
No forward-looking statement can be guaranteed and actual results may differ materially from those we project. Amgen's results may be affected by its ability to successfully market both new and existing products domestically and internationally, sales growth of recently launched products, difficulties or delays in manufacturing its products, and regulatory developments (domestic or foreign) involving current and future products and manufacturing facilities. In addition, sales of Amgen's products are affected by reimbursement policies imposed by third party payors, including governments, private insurance plans and managed care providers, and may be affected by domestic and international trends toward managed care and healthcare cost containment as well as possible U.S. legislation affecting pharmaceutical pricing and reimbursement. Government regulations and reimbursement policies may affect the development, usage and pricing of Amgen's products. Furthermore, Amgen's research, testing, pricing, marketing and other operations are subject to extensive regulation by domestic and foreign government regulatory authorities. Amgen or others could identify side effects or manufacturing problems with its products after they are on the market.
In addition, Amgen competes with other companies with respect to some of its marketed products as well as for the discovery and development of new products. Discovery or identification of new product candidates cannot be guaranteed and movement from concept to product is uncertain; consequently, there can be no guarantee that any particular product candidate will be successful and become a commercial product.
In addition, while Amgen routinely obtains patents for its products and technology, the protection offered by its patents and patent applications may be challenged, invalidated or circumvented by its competitors. Further, some raw materials, medical devices and component parts for Amgen's products are supplied by sole third party suppliers.
The statements in this press release that are not historical facts are forward-looking statements based on current expectations of future events that involve risks and uncertainties including, without limitation, risks associated with the inherent uncertainty of pharmaceutical research, product development, manufacturing, and commercialization, and economic conditions, including interest and currency exchange rate fluctuations, the impact of competitive or generic products, product liability and other types of lawsuits, the impact of legislative and regulatory compliance and obtaining approvals, and patents, and other risks and uncertainties, including those detailed from time to time in Wyeth's periodic reports, including quarterly reports on Form 10-Q and the Annual Report on Form 10-K, filed with the Securities and Exchange Commission. Actual results may vary materially from the forward-looking statements. Wyeth assumes no obligation to publicly update any forward-looking statements, whether as a result of new information, future events or otherwise.
View drug information on Enbrel.
"Since the rheumatoid arthritis approval in 1998, ENBREL has helped thousands of people better manage their disease," said Beth Seidenberg, M.D., chief medical officer and senior vice president of global development, Amgen. "This approval provides physicians with the opportunity to offer their patients an easy-to-use prefilled syringe that delivers the same drug patients and physicians have grown to trust."
The FDA approval was based on a study, which found that the ENBREL 50 mg/mL prefilled syringe was shown to be biologically equivalent to two 25 mg vials. The 25 mg formulation will still be available for juvenile rheumatoid arthritis patients and those that prefer that dosing method.
"This new delivery system can make it easier for patients to receive the proven efficacy and established tolerability of ENBREL," said Joseph Camardo, M.D., senior vice president, global medical affairs, Wyeth Pharmaceuticals. "It may be especially beneficial to people who have rheumatoid arthritis or active psoriatic arthritis, as their hands may be affected by the disabling joint destruction these conditions can cause."
ENBREL is a leading biologic treatment for moderately to severely active rheumatoid arthritis and is the first and only TNF inhibitor approved to treat chronic moderate to severe plaque psoriasis, active psoriatic arthritis, active ankylosing spondylitis (arthritis of the spine) and children with moderately to severely polyarticular-course active juvenile rheumatoid arthritis in patients who have had an inadequate response to one or more disease-modifying antirheumatic drugs (DMARDs).
ABOUT ENBREL
ENBREL is the only fully human TNF receptor approved to reduce signs and symptoms, induce major clinical response, improve physical function, and inhibit the progression of structural damage in patients with moderately to severely active rheumatoid arthritis (RA). ENBREL is also indicated to reduce the signs and symptoms and inhibit the progression of structural damage of active arthritis in patients with psoriatic arthritis. ENBREL is the only biologic therapy approved for first-line treatment of RA patients, and can be used alone or in combination with methotrexate.
ENBREL is also approved to reduce the signs and symptoms of moderately to severely active polyarticular-course juvenile rheumatoid arthritis (JRA) in patients who have had an inadequate response to one or more disease-modifying antirheumatic drugs (DMARDs). It is also the first biologic approved to treat the signs and symptoms in patients with active ankylosing spondylitis (AS). ENBREL is indicated for the treatment of adult patients (18 years or older) with chronic moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy.
ENBREL has been used by more than 250,000 patients worldwide across indications.
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 that are involved in the inflammatory process of RA, JRA, psoriasis, psoriatic arthritis and AS. The binding of ENBREL to TNF renders the bound TNF biologically inactive, resulting in significant reduction in inflammatory activity.
Since the product was first introduced, the following have been reported in patients using ENBREL:
-- Serious Infections
-- Many occurred in people prone to infection, such as those
with advanced or poorly controlled diabetes
-- Some serious infections were fatal
-- Rare cases of tuberculosis
-- What to do/Not to do
-- Do not start ENBREL if you have an infection or are allergic to ENBREL or its components.
-- Tell your doctor if you are prone to infection.
-- Stop ENBREL if a serious infection occurs.
-- Contact your doctor if you have questions about ENBREL or develop an infection.
-- Tell your doctor if you have ever been treated for heart failure.
-- Serious nervous system disorders such as multiple sclerosis, seizures, or inflammation of the nerves of the eyes
-- Tell your doctor if you have ever had any of these disorders or if you develop them after starting ENBREL.
-- Rare reports of serious blood disorders (some fatal)
-- Contact your doctor immediately if you develop symptoms such as persistent fever, bruising, bleeding, or paleness.
-- 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 and psoriasis 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.
-- ENBREL can also cause injection site reactions.
-- In a medical study of patients with JRA, infections, headaches, abdominal pain, vomiting, and nausea occurred more frequently than in adults.
-- The kinds of infections reported were generally mild and similar to those usually seen in children.
-- Other serious adverse reactions were reported rarely, including serious infections (2 percent) and depression/personality disorder (1 percent).
Amgen and Wyeth Pharmaceuticals, a division of Wyeth, market ENBREL in North America. Wyeth markets ENBREL outside of North America. Immunex Corporation, a wholly owned subsidiary of Amgen, manufactures ENBREL. Additional information about ENBREL, including full Prescribing Information, can be found on the Web site sponsored by the companies at enbrel or by calling toll free 888-4ENBREL (888-436-2735).
Amgen is a global biotechnology company that discovers, develops, manufactures and markets important human therapeutics based on advances in cellular and molecular biology. Wyeth Pharmaceuticals, a division of Wyeth, has leading products in the areas of women's health care, cardiovascular disease, central nervous system, inflammation, transplantation, hemophilia, oncology, vaccines and nutritional products. Wyeth is one of the world's largest research-driven pharmaceutical and health care products companies. It is a leader in the discovery, development, manufacturing, and marketing of pharmaceuticals, vaccines, biotechnology products and nonprescription medicines that improve the quality of life for people worldwide. The Company's major divisions include Wyeth Pharmaceuticals, Wyeth Consumer Healthcare, and Fort Dodge Animal Health.
This news release contains forward-looking statements that involve significant risks and uncertainties, including those discussed below and others that can be found in Amgen's Form 10-K for the year ended December 31, 2003, and in Amgen's periodic reports on Form 10-Q and Form 8-K. Amgen is providing this information as of the date of this news release and does not undertake any obligation to update any forward-looking statements contained in this document as a result of new information, future events or otherwise.
No forward-looking statement can be guaranteed and actual results may differ materially from those we project. Amgen's results may be affected by its ability to successfully market both new and existing products domestically and internationally, sales growth of recently launched products, difficulties or delays in manufacturing its products, and regulatory developments (domestic or foreign) involving current and future products and manufacturing facilities. In addition, sales of Amgen's products are affected by reimbursement policies imposed by third party payors, including governments, private insurance plans and managed care providers, and may be affected by domestic and international trends toward managed care and healthcare cost containment as well as possible U.S. legislation affecting pharmaceutical pricing and reimbursement. Government regulations and reimbursement policies may affect the development, usage and pricing of Amgen's products. Furthermore, Amgen's research, testing, pricing, marketing and other operations are subject to extensive regulation by domestic and foreign government regulatory authorities. Amgen or others could identify side effects or manufacturing problems with its products after they are on the market.
In addition, Amgen competes with other companies with respect to some of its marketed products as well as for the discovery and development of new products. Discovery or identification of new product candidates cannot be guaranteed and movement from concept to product is uncertain; consequently, there can be no guarantee that any particular product candidate will be successful and become a commercial product.
In addition, while Amgen routinely obtains patents for its products and technology, the protection offered by its patents and patent applications may be challenged, invalidated or circumvented by its competitors. Further, some raw materials, medical devices and component parts for Amgen's products are supplied by sole third party suppliers.
The statements in this press release that are not historical facts are forward-looking statements based on current expectations of future events that involve risks and uncertainties including, without limitation, risks associated with the inherent uncertainty of pharmaceutical research, product development, manufacturing, and commercialization, and economic conditions, including interest and currency exchange rate fluctuations, the impact of competitive or generic products, product liability and other types of lawsuits, the impact of legislative and regulatory compliance and obtaining approvals, and patents, and other risks and uncertainties, including those detailed from time to time in Wyeth's periodic reports, including quarterly reports on Form 10-Q and the Annual Report on Form 10-K, filed with the Securities and Exchange Commission. Actual results may vary materially from the forward-looking statements. Wyeth assumes no obligation to publicly update any forward-looking statements, whether as a result of new information, future events or otherwise.
View drug information on Enbrel.
четверг, 25 августа 2011 г.
Early Aggressive Treatment May Alter Course Of Rheumatoid Arthritis
Early administration of methotrexate and infliximab may lead to remission in patients with rheumatoid arthritis, according to research presented this week at the American College of Rheumatology Annual Scientific Meeting in Washington, DC.
Methotrexate and the injectable infliximab are among several disease-modifying antirheumatic drugs administered to reduce or prevent joint damage as well as preserve joint integrity. These drugs, often used in conjunction with non-steroidal anti-inflammatory drugs like ibuprofen, have greatly improved symptoms, function and quality of life for patients with rheumatoid arthritis.
Dutch rheumatologists, conducting a long-term BeSt ("Behandel Strategie?n" or "Treatment Strategies") study on 508 patients with early evidence of the rheumatoid arthritis, explored four strategies for treatment utilizing various combinations of these DMARDS. These strategies included: sequential monotherapy, monotherapy building up to combination therapy, and initial combination therapy using either prednisone or infliximab. All patients who started infliximab also were on methotrexate. In the case of adverse drug events requiring the discontinuation of methotrexate, an alternative DMARD (usually sulfasalazine) was started in combination with infliximab.
The initial combination therapies proved superior to initial monotherapy in gaining earlier improvement in functional ability and decreasing radiographic joint damage progression. After two years, 56% of patients treated with the initial combination of methotrexate and infliximab were able to discontinue infliximab without relapse, and subsequently taper methotrexate to 10 mg/week. A year later, 14% of all patients receiving initial treatment with infliximab tapered off all medication and are still in remission (no measurable signs of disease activity). Only four patients (out of the original 67 responders at two years) who were on methotrexate 10 mg/week had to increase methotrexate to 25 mg/week and restart infliximab during the third year because of a flare in disease activity.
Currently, the BeSt study includes the only large cohort of patients with early rheumatoid arthritis who have successfully discontinued infliximab after achieving low disease activity. Given many patients' ability to achieve remission after two years and taper medication to methotrexate 10 mg/week, BeSt researchers had added the goal of discontinuation to third-year follow-up.
"These three-year follow-up results indicate that initial treatment with methotrexate and infliximab may alter the course of early rheumatoid arthritis and, in many cases, move patients into remission," summarizes Sjoerd van der Kooij, MD, Leiden University Medical Center, Leiden, The Netherlands, an investigator in the study. "Data collected over the next years will determine whether treatment-free remission will last, and whether it represents not only clinical but also radiological suppression of disease activity."
The American College of Rheumatology is the professional organization for rheumatologists and health professionals who share a dedication to healing, preventing disability and curing arthritis and related rheumatic and musculoskeletal diseases. For more information on the ACR's annual meeting, see rheumatology/annual.
Presentation Number: 658
Remission Induction in Early Rheumatoid Arthritis (RA) with Initial Infliximab (IFX) and Methotrexate (MTX) Therapy: The Disease Course After IFX Discontinuation in The BeSt Trial
S. M. Van Der Kooij1, A. E. Van Der Bijl1, C. F. Allaart1, Y. P.M. Goekoop-Ruiterman1, J. K. De Vries-Bouwstra2, A. H. Gerards3, M. L. Westedt4, F. C. Breedveld1, B. A.C. Dijkmans2. 1LUMC, Leiden, The Netherlands; 2VUMC, Amsterdam, The Netherlands; 3Vlietland, Schiedam, The Netherlands; 4Bronovo, The Hague, The Netherlands
PURPOSE
To describe the clinical and radiological outcome of patients with early RA who discontinued IFX after good clinical response on initial treatment with IFX+MTX.
METHODS
In the BeSt study, a randomized clinical trial comparing 4 different treatment strategies in early RA, 120 patients in Group 4 (baseline DAS 4.3, 64% rheumatoid factor positive, 73% erosive) started treatment with IFX 3 mg/kg plus MTX 25 mg/week. If the DAS, calculated 1-2 weeks before each IFX infusion, was >2.4, IFX was increased (6, 7.5 and max. 10 mg/kg/8 weeks). If DAS was == 6 months, IFX was tapered to nil and next MTX was tapered to 10 mg/week. In the 3rd year, if DAS was = 6 months, MTX 10 mg/wk was tapered to nil. If the next DAS was >1.6, MTX 10 mg/week was restarted, then, if the DAS was >2.4, first MTX was increased to 25 mg/week, next IFX was restarted and if necessary increased. Baseline and 3-year Sharp-van der Heijde Scores (SHS) were assessed independently in random order by 2 physicians.
RESULT
After 2 years, 67/120 patients ('Responders', 56%) had successfully discontinued IFX and tapered MTX to (mean) 12.6 mg/week; 23/120 patients were on variable IFX dosages ('Continued Treatment') and 30 patients had failed on IFX+MTX and switched to other treatment steps.
After 3 years, median 26 months after IFX discontinuation, 61/67 (91%) of the 'Responders' (51% of all 120 patients) still had DAS =
Methotrexate and the injectable infliximab are among several disease-modifying antirheumatic drugs administered to reduce or prevent joint damage as well as preserve joint integrity. These drugs, often used in conjunction with non-steroidal anti-inflammatory drugs like ibuprofen, have greatly improved symptoms, function and quality of life for patients with rheumatoid arthritis.
Dutch rheumatologists, conducting a long-term BeSt ("Behandel Strategie?n" or "Treatment Strategies") study on 508 patients with early evidence of the rheumatoid arthritis, explored four strategies for treatment utilizing various combinations of these DMARDS. These strategies included: sequential monotherapy, monotherapy building up to combination therapy, and initial combination therapy using either prednisone or infliximab. All patients who started infliximab also were on methotrexate. In the case of adverse drug events requiring the discontinuation of methotrexate, an alternative DMARD (usually sulfasalazine) was started in combination with infliximab.
The initial combination therapies proved superior to initial monotherapy in gaining earlier improvement in functional ability and decreasing radiographic joint damage progression. After two years, 56% of patients treated with the initial combination of methotrexate and infliximab were able to discontinue infliximab without relapse, and subsequently taper methotrexate to 10 mg/week. A year later, 14% of all patients receiving initial treatment with infliximab tapered off all medication and are still in remission (no measurable signs of disease activity). Only four patients (out of the original 67 responders at two years) who were on methotrexate 10 mg/week had to increase methotrexate to 25 mg/week and restart infliximab during the third year because of a flare in disease activity.
Currently, the BeSt study includes the only large cohort of patients with early rheumatoid arthritis who have successfully discontinued infliximab after achieving low disease activity. Given many patients' ability to achieve remission after two years and taper medication to methotrexate 10 mg/week, BeSt researchers had added the goal of discontinuation to third-year follow-up.
"These three-year follow-up results indicate that initial treatment with methotrexate and infliximab may alter the course of early rheumatoid arthritis and, in many cases, move patients into remission," summarizes Sjoerd van der Kooij, MD, Leiden University Medical Center, Leiden, The Netherlands, an investigator in the study. "Data collected over the next years will determine whether treatment-free remission will last, and whether it represents not only clinical but also radiological suppression of disease activity."
The American College of Rheumatology is the professional organization for rheumatologists and health professionals who share a dedication to healing, preventing disability and curing arthritis and related rheumatic and musculoskeletal diseases. For more information on the ACR's annual meeting, see rheumatology/annual.
Presentation Number: 658
Remission Induction in Early Rheumatoid Arthritis (RA) with Initial Infliximab (IFX) and Methotrexate (MTX) Therapy: The Disease Course After IFX Discontinuation in The BeSt Trial
S. M. Van Der Kooij1, A. E. Van Der Bijl1, C. F. Allaart1, Y. P.M. Goekoop-Ruiterman1, J. K. De Vries-Bouwstra2, A. H. Gerards3, M. L. Westedt4, F. C. Breedveld1, B. A.C. Dijkmans2. 1LUMC, Leiden, The Netherlands; 2VUMC, Amsterdam, The Netherlands; 3Vlietland, Schiedam, The Netherlands; 4Bronovo, The Hague, The Netherlands
PURPOSE
To describe the clinical and radiological outcome of patients with early RA who discontinued IFX after good clinical response on initial treatment with IFX+MTX.
METHODS
In the BeSt study, a randomized clinical trial comparing 4 different treatment strategies in early RA, 120 patients in Group 4 (baseline DAS 4.3, 64% rheumatoid factor positive, 73% erosive) started treatment with IFX 3 mg/kg plus MTX 25 mg/week. If the DAS, calculated 1-2 weeks before each IFX infusion, was >2.4, IFX was increased (6, 7.5 and max. 10 mg/kg/8 weeks). If DAS was == 6 months, IFX was tapered to nil and next MTX was tapered to 10 mg/week. In the 3rd year, if DAS was = 6 months, MTX 10 mg/wk was tapered to nil. If the next DAS was >1.6, MTX 10 mg/week was restarted, then, if the DAS was >2.4, first MTX was increased to 25 mg/week, next IFX was restarted and if necessary increased. Baseline and 3-year Sharp-van der Heijde Scores (SHS) were assessed independently in random order by 2 physicians.
RESULT
After 2 years, 67/120 patients ('Responders', 56%) had successfully discontinued IFX and tapered MTX to (mean) 12.6 mg/week; 23/120 patients were on variable IFX dosages ('Continued Treatment') and 30 patients had failed on IFX+MTX and switched to other treatment steps.
After 3 years, median 26 months after IFX discontinuation, 61/67 (91%) of the 'Responders' (51% of all 120 patients) still had DAS =
понедельник, 22 августа 2011 г.
Launch Of Musculoskeletal Guidelines For GPs In Australia
A lack of evidence-based clinical musculoskeletal guidelines has prompted the Royal Australian College of General Practitioners (RACGP) to develop guidelines for GPs and other primary health care professionals covering musculoskeletal prevention and early treatment.
RACGP President, Dr Chris Mitchell, said that the new RACGP musculoskeletal guidelines are significant because most current clinical guidelines available are consensus-based, agreed on by peers, rather than evidence-based and there is very limited information on juvenile idiopathic arthritis.
The first three of four guidelines cover osteoarthritis, rheumatoid arthritis and juvenile idiopathic arthritis and will be launched on Friday, 11 September. The guidelines are available for free download on the RACGP website at racgp.au/guidelines. The other guidelines on osteoporosis will be available on the RACGP website as soon as they become available.
Each guideline includes:
- Algorithms (diagnosis and management) that are designed to be reference tools during consultations
- Recommendations that provide a summary and grading of the available evidence
"These guidelines are a first for general practice in Australia. We are pleased to see that there has already been significant international interest in this important work," Dr Mitchell said.
"The guidelines focus strongly on the early diagnosis and management because there is an opportunity within the first few months of disease onset to provide treatment that effectively limits structural damage and improves health outcomes."
"Early and proper diagnosis is paramount in effectively managing severe forms of arthritis. We encourage GPs to actively use these step-by-step guidelines to ensure their patients have the opportunity of accessing suitable and timely treatments for their condition," said Arthritis Australia's CEO, Ainslie Cahill.
The RACGP has been working with expert working groups (general practitioner and other primary health care professionals) and a consultant appointed by the National Health Medical Research Council (NHMRC) to develop these four guidelines.
These guidelines are one of the first to use the NHMRC Evidence based Matrix (NHMRC additional levels of evidence and gradings of recommendations for developers of guidelines), which greatly assisted the grading of the recommendations.
This project has been funded by the Australian Government Department of Health and Ageing and the guidelines have been developed to the requirements of the NHMRC.
Source
RACGP
RACGP President, Dr Chris Mitchell, said that the new RACGP musculoskeletal guidelines are significant because most current clinical guidelines available are consensus-based, agreed on by peers, rather than evidence-based and there is very limited information on juvenile idiopathic arthritis.
The first three of four guidelines cover osteoarthritis, rheumatoid arthritis and juvenile idiopathic arthritis and will be launched on Friday, 11 September. The guidelines are available for free download on the RACGP website at racgp.au/guidelines. The other guidelines on osteoporosis will be available on the RACGP website as soon as they become available.
Each guideline includes:
- Algorithms (diagnosis and management) that are designed to be reference tools during consultations
- Recommendations that provide a summary and grading of the available evidence
"These guidelines are a first for general practice in Australia. We are pleased to see that there has already been significant international interest in this important work," Dr Mitchell said.
"The guidelines focus strongly on the early diagnosis and management because there is an opportunity within the first few months of disease onset to provide treatment that effectively limits structural damage and improves health outcomes."
"Early and proper diagnosis is paramount in effectively managing severe forms of arthritis. We encourage GPs to actively use these step-by-step guidelines to ensure their patients have the opportunity of accessing suitable and timely treatments for their condition," said Arthritis Australia's CEO, Ainslie Cahill.
The RACGP has been working with expert working groups (general practitioner and other primary health care professionals) and a consultant appointed by the National Health Medical Research Council (NHMRC) to develop these four guidelines.
These guidelines are one of the first to use the NHMRC Evidence based Matrix (NHMRC additional levels of evidence and gradings of recommendations for developers of guidelines), which greatly assisted the grading of the recommendations.
This project has been funded by the Australian Government Department of Health and Ageing and the guidelines have been developed to the requirements of the NHMRC.
Source
RACGP
пятница, 19 августа 2011 г.
Rheumatoid Arthritis Rituxan(reg) Significantly Improves Symptoms In Patients, Phase III Study
Genentech, Inc (NYSE: DNA), Biogen Idec (Nasdaq: BIIB) and Roche (SWX Zurich) announced today that a Phase III clinical
study of Rituxan(reg) (Rituximab) met its primary endpoint of a greater proportion of Rituxan-treated patients achieving an
American College of Rheumatology (ACR) 20 response at week 24, compared to placebo. The study included patients with active
rheumatoid arthritis (RA) who have had an inadequate response or were intolerant to prior treatment with one or more anti-TNF
therapies.
In this study, known as REFLEX (Randomized Evaluation of Long-term Efficacy of Rituximab in RA), patients who received a
single treatment course of two infusions of Rituxan with a stable dose of methotrexate (MTX) displayed a statistically
significant improvement in symptoms compared to patients who received placebo and MTX. Further analyses of the data are
ongoing and will be submitted for presentation at an upcoming medical meeting.
A preliminary analysis of the data did not reveal any unexpected safety signals. The most common side effects in the Rituxan
arm included headache, upper respiratory tract infection and nasopharyngitis. The reported rate of serious adverse events was
comparable across the two treatment arms.
"These results continue to support the potential of Rituxan as a new therapeutic option for RA," said Burt Adelman, M.D.,
executive vice president, development, Biogen Idec. "We look forward to sharing the REFLEX data in our discussions with the
FDA."
"These are the first Phase III Rituxan data to demonstrate clinical improvement in this difficult-to-treat RA patient
population. The findings add to the growing body of evidence that selectively targeting B cells may provide an important new
treatment approach for this debilitating disease," said Hal Barron, M.D., Genentech's senior vice president, development and
chief medical officer. "While we are encouraged that the preliminary safety results are similar to previous studies, we
recognize the importance of monitoring long-term safety in RA patients treated with Rituxan."
These new Phase III data follow recent positive preliminary findings from a Phase IIb study that evaluated the efficacy and
safety of Rituxan in moderate-to-severe RA patients who failed prior treatment with at least one disease-modifying
anti-rheumatic drug (DMARD).
About the Study
A total of 520 patients from the United States, Canada and Europe were randomized to receive either Rituxan (1000 mg i.v. on
days one and 15) or placebo in this multi-center, double-blind, placebo-controlled study. All patients received a stable dose
of MTX and a two-week course of corticosteroids.
ACR 20 indicates a 20 percent improvement in the number of swollen and tender joints, as well as a 20 percent improvement
compared with baseline in three of five disease-activity measures: patient assessment, physician assessment, pain scale,
Health Assessment Questionnaire and the value for one acute phase reactant (erythrocyte sedimentation rate or C-reactive
protein).
About RA
RA is a debilitating autoimmune disease that affects more than two million Americans 1 and hinders the daily activities of
sufferers. RA occurs when the immune system inappropriately attacks joint tissue, causing chronic inflammation and
irreversible destruction of cartilage, tendons and bones, often resulting in disability. While RA has traditionally been
considered a T-cell-mediated disease, emerging research suggests that other immune cells called B cells may play multiple
roles in the pathophysiology of RA including autoantibody production, T-cell activation and cytokine production. Common RA
symptoms include inflammation of the joints, swelling, fatigue, stiffness and pain. Additionally, since RA is a systemic
disease, it can have effects in other tissues such as the lungs, eyes and bone marrow.
About Rituxan
Rituxan is a therapeutic antibody that targets and selectively depletes peripheral CD20 positive B cells without targeting
stem cells or existing plasma cells. B cells may play multiple roles in the pathophysiology of RA. Rituxan is also being
investigated in other autoimmune diseases including lupus, multiple sclerosis and ANCA associated vasculitis.
Rituxan received initial FDA approval in November 1997 for the treatment of relapsed or refractory low-grade or follicular,
CD20 positive, B cell non-Hodgkin's lymphoma (NHL). It also was approved in the European Union (EU) under the trade name
MabThera(reg) in June 1998. Genentech and Biogen Idec co-market Rituxan in the United States and Roche markets MabThera in the
rest of the world, except Japan, where Rituxan is co-marketed with Zenyaku Kogyo Co. Ltd. Rituxan has been used to treat more
than 380,000 patients worldwide. For a copy of the Rituxan full prescribing information, including Boxed Warning, please call
1-800-821-8590 or visit gene.
Rituxan Safety Profile in NHL
In NHL patients, the majority of patients experience infusion-related symptoms with their first Rituxan infusion. These
symptoms include but are not limited to: flu-like fever, chills/rigors, nausea, urticaria, headache, bronchospasm, angioedema
and hypotension. These symptoms vary in severity and generally are reversible with medical intervention. In rare instances,
severe and fatal infusion-related reactions have occurred, nearly all of which have been associated with the first Rituxan
infusion. These events appear as manifestations of an infusion-related complex and include hypoxia, pulmonary infiltrates,
acute respiratory distress syndrome, myocardial infarction, ventricular fibrillation, cardiogenic shock and tumor lysis
syndrome. Patients who develop clinically significant infusion-related cardiopulmonary events should have their Rituxan
infusion discontinued and receive medical treatment.
In rare instances, severe mucocutaneous skin reactions have occurred that may be associated with Rituxan therapy. Many of
these reactions have been described as paraneoplastic pemphigus and are known to be associated with various B cell lymphomas,
particularly NHL and chronic lymphocytic leukemia. Patients who develop a severe mucocutaneous skin reaction should have
Rituxan discontinued and receive appropriate medical treatment, including a skin biopsy to guide therapy.
About Genentech
Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes biotherapeutics for
significant unmet medical needs. A considerable number of the currently approved biotechnology products originated from or
are based on Genentech science. Genentech manufactures and commercializes multiple biotechnology products directly in the
United States and licenses several additional products to other companies. The company has headquarters in South San
Francisco, California and is traded on the New York Stock Exchange under the symbol DNA. For additional information about the
company, please visit gene.
About Biogen Idec
Biogen Idec creates new standards of care in oncology and immunology. As a global leader in the development, manufacturing
and commercialization of novel therapies, Biogen Idec transforms scientific discoveries into advances in human healthcare.
For product labeling, press releases and additional information about the company, please visit biogenidec.
About Roche
Headquartered in Basel, Switzerland, Roche is one of the world's leading research-focused healthcare groups in the fields of
pharmaceuticals and diagnostics. As a supplier of innovative products and services for the early detection, prevention,
diagnosis and treatment of disease, the Group contributes on a broad range of fronts to improving people's health and quality
of life. Roche is a world leader in diagnostics, the leading supplier of medicines for cancer and transplantation and a
market leader in virology. In 2004 sales by the Pharmaceuticals Division totaled 21.7 billion Swiss francs, while the
Diagnostics Division posted sales of 7.8 billion Swiss francs. Roche employs roughly 65,000 people in 150 countries and has
R&D agreements and strategic alliances with numerous partners, including majority ownership interests in Genentech and
Chugai.
1 American College of Rheumatology, 2005,
rheumatology/public/factsheets/ra.asp?aud=pat
View drug information on Rituxan.
study of Rituxan(reg) (Rituximab) met its primary endpoint of a greater proportion of Rituxan-treated patients achieving an
American College of Rheumatology (ACR) 20 response at week 24, compared to placebo. The study included patients with active
rheumatoid arthritis (RA) who have had an inadequate response or were intolerant to prior treatment with one or more anti-TNF
therapies.
In this study, known as REFLEX (Randomized Evaluation of Long-term Efficacy of Rituximab in RA), patients who received a
single treatment course of two infusions of Rituxan with a stable dose of methotrexate (MTX) displayed a statistically
significant improvement in symptoms compared to patients who received placebo and MTX. Further analyses of the data are
ongoing and will be submitted for presentation at an upcoming medical meeting.
A preliminary analysis of the data did not reveal any unexpected safety signals. The most common side effects in the Rituxan
arm included headache, upper respiratory tract infection and nasopharyngitis. The reported rate of serious adverse events was
comparable across the two treatment arms.
"These results continue to support the potential of Rituxan as a new therapeutic option for RA," said Burt Adelman, M.D.,
executive vice president, development, Biogen Idec. "We look forward to sharing the REFLEX data in our discussions with the
FDA."
"These are the first Phase III Rituxan data to demonstrate clinical improvement in this difficult-to-treat RA patient
population. The findings add to the growing body of evidence that selectively targeting B cells may provide an important new
treatment approach for this debilitating disease," said Hal Barron, M.D., Genentech's senior vice president, development and
chief medical officer. "While we are encouraged that the preliminary safety results are similar to previous studies, we
recognize the importance of monitoring long-term safety in RA patients treated with Rituxan."
These new Phase III data follow recent positive preliminary findings from a Phase IIb study that evaluated the efficacy and
safety of Rituxan in moderate-to-severe RA patients who failed prior treatment with at least one disease-modifying
anti-rheumatic drug (DMARD).
About the Study
A total of 520 patients from the United States, Canada and Europe were randomized to receive either Rituxan (1000 mg i.v. on
days one and 15) or placebo in this multi-center, double-blind, placebo-controlled study. All patients received a stable dose
of MTX and a two-week course of corticosteroids.
ACR 20 indicates a 20 percent improvement in the number of swollen and tender joints, as well as a 20 percent improvement
compared with baseline in three of five disease-activity measures: patient assessment, physician assessment, pain scale,
Health Assessment Questionnaire and the value for one acute phase reactant (erythrocyte sedimentation rate or C-reactive
protein).
About RA
RA is a debilitating autoimmune disease that affects more than two million Americans 1 and hinders the daily activities of
sufferers. RA occurs when the immune system inappropriately attacks joint tissue, causing chronic inflammation and
irreversible destruction of cartilage, tendons and bones, often resulting in disability. While RA has traditionally been
considered a T-cell-mediated disease, emerging research suggests that other immune cells called B cells may play multiple
roles in the pathophysiology of RA including autoantibody production, T-cell activation and cytokine production. Common RA
symptoms include inflammation of the joints, swelling, fatigue, stiffness and pain. Additionally, since RA is a systemic
disease, it can have effects in other tissues such as the lungs, eyes and bone marrow.
About Rituxan
Rituxan is a therapeutic antibody that targets and selectively depletes peripheral CD20 positive B cells without targeting
stem cells or existing plasma cells. B cells may play multiple roles in the pathophysiology of RA. Rituxan is also being
investigated in other autoimmune diseases including lupus, multiple sclerosis and ANCA associated vasculitis.
Rituxan received initial FDA approval in November 1997 for the treatment of relapsed or refractory low-grade or follicular,
CD20 positive, B cell non-Hodgkin's lymphoma (NHL). It also was approved in the European Union (EU) under the trade name
MabThera(reg) in June 1998. Genentech and Biogen Idec co-market Rituxan in the United States and Roche markets MabThera in the
rest of the world, except Japan, where Rituxan is co-marketed with Zenyaku Kogyo Co. Ltd. Rituxan has been used to treat more
than 380,000 patients worldwide. For a copy of the Rituxan full prescribing information, including Boxed Warning, please call
1-800-821-8590 or visit gene.
Rituxan Safety Profile in NHL
In NHL patients, the majority of patients experience infusion-related symptoms with their first Rituxan infusion. These
symptoms include but are not limited to: flu-like fever, chills/rigors, nausea, urticaria, headache, bronchospasm, angioedema
and hypotension. These symptoms vary in severity and generally are reversible with medical intervention. In rare instances,
severe and fatal infusion-related reactions have occurred, nearly all of which have been associated with the first Rituxan
infusion. These events appear as manifestations of an infusion-related complex and include hypoxia, pulmonary infiltrates,
acute respiratory distress syndrome, myocardial infarction, ventricular fibrillation, cardiogenic shock and tumor lysis
syndrome. Patients who develop clinically significant infusion-related cardiopulmonary events should have their Rituxan
infusion discontinued and receive medical treatment.
In rare instances, severe mucocutaneous skin reactions have occurred that may be associated with Rituxan therapy. Many of
these reactions have been described as paraneoplastic pemphigus and are known to be associated with various B cell lymphomas,
particularly NHL and chronic lymphocytic leukemia. Patients who develop a severe mucocutaneous skin reaction should have
Rituxan discontinued and receive appropriate medical treatment, including a skin biopsy to guide therapy.
About Genentech
Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes biotherapeutics for
significant unmet medical needs. A considerable number of the currently approved biotechnology products originated from or
are based on Genentech science. Genentech manufactures and commercializes multiple biotechnology products directly in the
United States and licenses several additional products to other companies. The company has headquarters in South San
Francisco, California and is traded on the New York Stock Exchange under the symbol DNA. For additional information about the
company, please visit gene.
About Biogen Idec
Biogen Idec creates new standards of care in oncology and immunology. As a global leader in the development, manufacturing
and commercialization of novel therapies, Biogen Idec transforms scientific discoveries into advances in human healthcare.
For product labeling, press releases and additional information about the company, please visit biogenidec.
About Roche
Headquartered in Basel, Switzerland, Roche is one of the world's leading research-focused healthcare groups in the fields of
pharmaceuticals and diagnostics. As a supplier of innovative products and services for the early detection, prevention,
diagnosis and treatment of disease, the Group contributes on a broad range of fronts to improving people's health and quality
of life. Roche is a world leader in diagnostics, the leading supplier of medicines for cancer and transplantation and a
market leader in virology. In 2004 sales by the Pharmaceuticals Division totaled 21.7 billion Swiss francs, while the
Diagnostics Division posted sales of 7.8 billion Swiss francs. Roche employs roughly 65,000 people in 150 countries and has
R&D agreements and strategic alliances with numerous partners, including majority ownership interests in Genentech and
Chugai.
1 American College of Rheumatology, 2005,
rheumatology/public/factsheets/ra.asp?aud=pat
View drug information on Rituxan.
вторник, 16 августа 2011 г.
Longer Treatment For Juvenile Idiopathic Arthritis During Remission Does Not Appear To Reduce Relapse Rate
For patients with juvenile idiopathic arthritis in remission, withdrawal of treatment with the drug methotrexate over 12 months vs. 6 months did not reduce the rate of relapse, according to a study in the April 7 issue of JAMA.
New therapies have improved the remission rate in chronic inflammatory disorders such as juvenile idiopathic arthritis (JIA; persistent or recurring inflammation of the joints similar to rheumatoid arthritis but beginning at or before age 16). "... physicians have to balance the risk of doing too little (e.g., withdrawing medication and provoking flares [relapses]) vs. the risk of doing too much (e.g., continuing medication despite a stable remission and thereby accepting the risk of adverse effects). While evidence-based advice for starting therapies in active disease is available, no controlled data exist to suggest the need for treatment continuation after remission is achieved," the authors write.
Dirk Foell, M.D., of the University of Muenster, Germany, and colleagues analyzed whether the duration of methotrexate therapy during clinical remission of JIA influences the rate of flares after withdrawal, and also examined whether patients at risk for a flare may be identified with use of the biomarker myeloid-related protein (MRP) 8 and MRP 14 (MRP8/14), which has been shown to be a marker of subclinical disease activity not detectable by laboratory tests. The randomized clinical trial included 364 patients (median [midpoint] age, 11.0 years) with JIA recruited in 61 centers from 29 countries between February 2005 and June 2006. Patients were included at first confirmation of clinical remission while continuing medication. At the time of therapy withdrawal, levels of MRP8/14 were determined.
Patients were randomly assigned to continue with methotrexate therapy for either 6 months (group 1 [n = 183]) or 12 months (group 2 [n = 181]) after the beginning of disease remission.
Analyses indicated relapse within 24 months after the inclusion into the study in 98 of 183 patients (56.7 percent) in group 1 and 94 of 181(55.6 percent) in group 2. The median relapse-free interval after inclusion was 21 months in group 1 and 23 months in group 2. Median follow-up duration after inclusion was 34.2 and 34.3 months in groups 1 and 2, respectively. In the 297 patients who stopped therapy while in remission, 39.6 percent in group 1 and 39.5 percent in group 2 had a flare within 1 year.
"Levels of MRP8/14 during remission were significantly higher in patients who subsequently developed flares compared with patients maintaining stable remission. Low MRP8/14 levels indicated a low risk of flares within the next 3 months following the biomarker test," the authors write.
"These data indicate a need for the stratification of patients with chronic inflammatory diseases to ensure that the intensity of treatment is adjusted to the patients' individual needs."
The researchers add that it cannot be recommended that methotrexate therapy be continued in all patients for longer than 6 months after remission is induced.
JAMA. 2010;303[13]:1266-1273.
Source
Journal Of the American Medical Association
New therapies have improved the remission rate in chronic inflammatory disorders such as juvenile idiopathic arthritis (JIA; persistent or recurring inflammation of the joints similar to rheumatoid arthritis but beginning at or before age 16). "... physicians have to balance the risk of doing too little (e.g., withdrawing medication and provoking flares [relapses]) vs. the risk of doing too much (e.g., continuing medication despite a stable remission and thereby accepting the risk of adverse effects). While evidence-based advice for starting therapies in active disease is available, no controlled data exist to suggest the need for treatment continuation after remission is achieved," the authors write.
Dirk Foell, M.D., of the University of Muenster, Germany, and colleagues analyzed whether the duration of methotrexate therapy during clinical remission of JIA influences the rate of flares after withdrawal, and also examined whether patients at risk for a flare may be identified with use of the biomarker myeloid-related protein (MRP) 8 and MRP 14 (MRP8/14), which has been shown to be a marker of subclinical disease activity not detectable by laboratory tests. The randomized clinical trial included 364 patients (median [midpoint] age, 11.0 years) with JIA recruited in 61 centers from 29 countries between February 2005 and June 2006. Patients were included at first confirmation of clinical remission while continuing medication. At the time of therapy withdrawal, levels of MRP8/14 were determined.
Patients were randomly assigned to continue with methotrexate therapy for either 6 months (group 1 [n = 183]) or 12 months (group 2 [n = 181]) after the beginning of disease remission.
Analyses indicated relapse within 24 months after the inclusion into the study in 98 of 183 patients (56.7 percent) in group 1 and 94 of 181(55.6 percent) in group 2. The median relapse-free interval after inclusion was 21 months in group 1 and 23 months in group 2. Median follow-up duration after inclusion was 34.2 and 34.3 months in groups 1 and 2, respectively. In the 297 patients who stopped therapy while in remission, 39.6 percent in group 1 and 39.5 percent in group 2 had a flare within 1 year.
"Levels of MRP8/14 during remission were significantly higher in patients who subsequently developed flares compared with patients maintaining stable remission. Low MRP8/14 levels indicated a low risk of flares within the next 3 months following the biomarker test," the authors write.
"These data indicate a need for the stratification of patients with chronic inflammatory diseases to ensure that the intensity of treatment is adjusted to the patients' individual needs."
The researchers add that it cannot be recommended that methotrexate therapy be continued in all patients for longer than 6 months after remission is induced.
JAMA. 2010;303[13]:1266-1273.
Source
Journal Of the American Medical Association
суббота, 13 августа 2011 г.
Majority Of Ontarians Suffering From Rheumatoid Arthritis Not Receiving Needed Speciality Care
Nearly 60 per cent of Ontarians with rheumatoid arthritis - an autoimmune disease that causes chronic inflammation of the joints - were not seen by a specialist within a one year period to treat the debilitating disease, according to a new study. Even more concerning is that women of child-bearing age are less likely to see a specialist than women 45 or older, say researchers from St. Michael's Hospital, the Institute for Clinical and Evaluative Sciences (ICES), and Women's College Hospital.
"People think the aches and pains associated with arthritis are a normal part of aging, leading to delays in seeking care," says Dr. Gillian Hawker, senior scientist at Women's College Research Institute and adjunct scientist at ICES. "But we know early diagnosis and treatment, especially within the first three to six months, is critical to preventing the long-term disability caused by rheumatoid arthritis."
Dr. Hawker is the lead author of the latest chapter of the Project for an Ontario Women's Health Evidence-Based Report (POWER) study. The joint study between St. Michael's Hospital and the Institute for Clinical Evaluative Sciences (ICES) - is the first in the province to provide a comprehensive overview of women's health in relation to gender, income, education, ethnicity and geography. Funded by Echo: Improving Women's Health in Ontario, an agency of the Ontario Ministry of Health and Long-Term Care, the results from the POWER Study are available for policymakers and health-care providers to improve access, quality and outcomes of care for Ontario women.
In Ontario, an estimated 55,000 women and 22,000 men have been diagnosed with rheumatoid arthritis, with women twice as likely to be affected as men.
"Unfortunately, only 42 per cent of women with rheumatoid arthritis in Ontario see specialists each year, says Dr. Arlene Bierman, a physician at St. Michael's Hospital and principal investigator of the POWER Study. "Low income women are less likely to have seen a specialist than those with higher incomes and a person's likelihood of seeing a specialist depends on where they live in the province. Access to these services is important and there is much that can be done to improve this access through innovations in how we organize and deliver care for chronic disease."
Studies show that primary care physicians may fail to refer patients to specialists because they lack confidence in performing the joint exams necessary to identify and diagnose inflammatory arthritis. And with a limited number of arthritis specialists - only 350 in Canada - including some who are strictly academics and don't see patients, access to speciality care may be limited.
For 45-year-old Lynn Robinson, the lack of early diagnosis and treatment kept her off work and in severe pain for months.
"Each day, the pain became progressively worse until I couldn't dress myself, brush my teeth or even hold a pen," said Robinson, who first began experiencing the symptoms of rheumatoid arthritis in 2008. "I was off work and in excruciating pain. My doctor dismissed the idea that the symptoms could be arthritis until I finally pushed to see a specialist who confirmed my suspicion. Now I'm on treatment and have been able to resume my daily activities, pain free."
The POWER study just released examined the impact of musculoskeletal conditions - diseases that affect the bones, ligaments, tendons, muscles and joints - on health status and disability and quality of care for Ontarians with osteoarthritis and osteoporosis. Key findings include:
About 40 per cent of women and 35 per cent of men living with a musculoskeletal disease, including arthritis, also suffer from at least one other common chronic condition, such as diabetes or heart disease.
Women who have musculoskeletal disease have higher rates of disability than men with these conditions. Nearly 40 per cent of women and about 23 per cent of men living with musculoskeletal disease reported moderate to severe disability including limitations to their daily activities such as housework, laundry, grocery shopping, dressing, or washing.
Physical therapy is important to managing musculoskeletal conditions. But only 15 per cent of adults with these conditions reported seeing a physiotherapist at least once in the previous year.
Gaps in the care of osteoporosis - a common musculoskeletal disease - persist. Two thirds of men and women who required it after a fracture did not receive a bone mineral density test or medication to reduce the risk of a subsequent fracture.
"The findings reinforce what we've been seeing in previous chapters," says Pat Campbell, Echo CEO. "There is a need to improve access to services and strengthen the integration of services across our health-care system. Policy-makers need to address these issues to ensure equity and quality care for all."
Source:
Julie Saccone
St. Michael's Hospital
"People think the aches and pains associated with arthritis are a normal part of aging, leading to delays in seeking care," says Dr. Gillian Hawker, senior scientist at Women's College Research Institute and adjunct scientist at ICES. "But we know early diagnosis and treatment, especially within the first three to six months, is critical to preventing the long-term disability caused by rheumatoid arthritis."
Dr. Hawker is the lead author of the latest chapter of the Project for an Ontario Women's Health Evidence-Based Report (POWER) study. The joint study between St. Michael's Hospital and the Institute for Clinical Evaluative Sciences (ICES) - is the first in the province to provide a comprehensive overview of women's health in relation to gender, income, education, ethnicity and geography. Funded by Echo: Improving Women's Health in Ontario, an agency of the Ontario Ministry of Health and Long-Term Care, the results from the POWER Study are available for policymakers and health-care providers to improve access, quality and outcomes of care for Ontario women.
In Ontario, an estimated 55,000 women and 22,000 men have been diagnosed with rheumatoid arthritis, with women twice as likely to be affected as men.
"Unfortunately, only 42 per cent of women with rheumatoid arthritis in Ontario see specialists each year, says Dr. Arlene Bierman, a physician at St. Michael's Hospital and principal investigator of the POWER Study. "Low income women are less likely to have seen a specialist than those with higher incomes and a person's likelihood of seeing a specialist depends on where they live in the province. Access to these services is important and there is much that can be done to improve this access through innovations in how we organize and deliver care for chronic disease."
Studies show that primary care physicians may fail to refer patients to specialists because they lack confidence in performing the joint exams necessary to identify and diagnose inflammatory arthritis. And with a limited number of arthritis specialists - only 350 in Canada - including some who are strictly academics and don't see patients, access to speciality care may be limited.
For 45-year-old Lynn Robinson, the lack of early diagnosis and treatment kept her off work and in severe pain for months.
"Each day, the pain became progressively worse until I couldn't dress myself, brush my teeth or even hold a pen," said Robinson, who first began experiencing the symptoms of rheumatoid arthritis in 2008. "I was off work and in excruciating pain. My doctor dismissed the idea that the symptoms could be arthritis until I finally pushed to see a specialist who confirmed my suspicion. Now I'm on treatment and have been able to resume my daily activities, pain free."
The POWER study just released examined the impact of musculoskeletal conditions - diseases that affect the bones, ligaments, tendons, muscles and joints - on health status and disability and quality of care for Ontarians with osteoarthritis and osteoporosis. Key findings include:
About 40 per cent of women and 35 per cent of men living with a musculoskeletal disease, including arthritis, also suffer from at least one other common chronic condition, such as diabetes or heart disease.
Women who have musculoskeletal disease have higher rates of disability than men with these conditions. Nearly 40 per cent of women and about 23 per cent of men living with musculoskeletal disease reported moderate to severe disability including limitations to their daily activities such as housework, laundry, grocery shopping, dressing, or washing.
Physical therapy is important to managing musculoskeletal conditions. But only 15 per cent of adults with these conditions reported seeing a physiotherapist at least once in the previous year.
Gaps in the care of osteoporosis - a common musculoskeletal disease - persist. Two thirds of men and women who required it after a fracture did not receive a bone mineral density test or medication to reduce the risk of a subsequent fracture.
"The findings reinforce what we've been seeing in previous chapters," says Pat Campbell, Echo CEO. "There is a need to improve access to services and strengthen the integration of services across our health-care system. Policy-makers need to address these issues to ensure equity and quality care for all."
Source:
Julie Saccone
St. Michael's Hospital
среда, 10 августа 2011 г.
Highlights From EULAR 2008, The Annual European Congress Of Rheumatology
Half of patients with early rheumatoid arthritis treated with the anti-tumour necrosis factor inhibitor (anti-TNF) infliximab plus methotrexate achieve remission, and up to one in five achieve drug-free remission, according to five-year follow-up results from the BeSt study.
Patients treated initially with a combination of infliximab plus methotrexate achieved significantly better functional ability than those given other treatment regimens.
The Dutch BeSt (Behandel Strategie?«n) study randomised 508 patients with recent-onset rheumatoid arthritis to one of the four most frequently used treatment strategies:
1. Sequential monotherapy - starting with one drug, then trying other types of drug on their own
2. Step-up combination therapy - starting with one drug, then adding on a second, and third or fourth drug
3. Initial combination including tapered high-dose prednisone
4. Initial combination therapy with infliximab plus methotrexate
The patients were monitored intensively and their treatment adjusted to keep their disease activity score (DAS) low (i.e. below 2.4).
At the end of five years, 51% of patients treated with initial combination therapy with infliximab plus methotrexate and a similar number of those give sequential monotherapy were in remission (Disease Activity Score < 1.6), compared to 45% of those treated with step-up combination therapy and 42% of patients treatment with initial combination including prednisone.
Of these remissions, 39%, 46%, 65% and 81% was achieved with the initial treatment step in treatments groups 1 to 4 respectively (p
Reporting the findings at EULAR, Dr Naomi Klarenbeek, also from Leiden University, said: "Over time, patients treated with an initial combination of infliximab plus methotrexate have significantly better functional ability than patients on other treatment strategies."
Dr Andrew Ost?¶r, consultant rheumatologist at Addenbrooke's Hospital, Cambridge, UK, commented: "Patients with aggressive early rheumatoid arthritis potentially do better when treated with initial combination therapy including a biologic. They clearly improved more rapidly than patients treated with sequential monotherapy or step-up combination therapy. Early improvement is important for patients' confidence in their treatment." He added: "Continuous monitoring and tight disease control - based on DAS score - is important in optimising therapy for individual patients."1
Infliximab better than DMARDs in RA patients failing on methotrexate
Adding infliximab achieves significantly better response than adding the conventional disease modifying antirheumatic drugs (DMARDs) sulfasalazine plus hydroxychloroquine in patients with early rheumatoid arthritis failing initial methotrexate monotherapy, a Swedish study has shown.
The SWEFOT trial was designed to compare two strategies in patients with early RA who had failed an initial 3-4 months treatment with methotrexate monotherapy. Researchers initially treated 487 patients with early RA, with symptoms for less than one year, with methotrexate (up to 20mg/week).
After three to four months, the 258 patients who had not achieved remission (defined as DAS28 < 3.2) and who were unable to tolerate methotrexate were randomised to DMARD therapy with sulfasalazine plus hydroxychloroquine or to infliximab (3mg/kg/infusion, given at 0, 2, 6 weeks, then every 8 weeks). Patients were allowed to switch therapy once (to cyclosporine in the DMARD group and to etanercept in the anti-TNF group) if they were unable to tolerate their treatment.
Results reported at EULAR showed that just over one-quarter (26%) of patients treated with DMARD therapy achieved a EULAR good response after 12 months, compared to 42% of those treated with infliximab (p
Patients treated initially with a combination of infliximab plus methotrexate achieved significantly better functional ability than those given other treatment regimens.
The Dutch BeSt (Behandel Strategie?«n) study randomised 508 patients with recent-onset rheumatoid arthritis to one of the four most frequently used treatment strategies:
1. Sequential monotherapy - starting with one drug, then trying other types of drug on their own
2. Step-up combination therapy - starting with one drug, then adding on a second, and third or fourth drug
3. Initial combination including tapered high-dose prednisone
4. Initial combination therapy with infliximab plus methotrexate
The patients were monitored intensively and their treatment adjusted to keep their disease activity score (DAS) low (i.e. below 2.4).
At the end of five years, 51% of patients treated with initial combination therapy with infliximab plus methotrexate and a similar number of those give sequential monotherapy were in remission (Disease Activity Score < 1.6), compared to 45% of those treated with step-up combination therapy and 42% of patients treatment with initial combination including prednisone.
Of these remissions, 39%, 46%, 65% and 81% was achieved with the initial treatment step in treatments groups 1 to 4 respectively (p
Reporting the findings at EULAR, Dr Naomi Klarenbeek, also from Leiden University, said: "Over time, patients treated with an initial combination of infliximab plus methotrexate have significantly better functional ability than patients on other treatment strategies."
Dr Andrew Ost?¶r, consultant rheumatologist at Addenbrooke's Hospital, Cambridge, UK, commented: "Patients with aggressive early rheumatoid arthritis potentially do better when treated with initial combination therapy including a biologic. They clearly improved more rapidly than patients treated with sequential monotherapy or step-up combination therapy. Early improvement is important for patients' confidence in their treatment." He added: "Continuous monitoring and tight disease control - based on DAS score - is important in optimising therapy for individual patients."1
Infliximab better than DMARDs in RA patients failing on methotrexate
Adding infliximab achieves significantly better response than adding the conventional disease modifying antirheumatic drugs (DMARDs) sulfasalazine plus hydroxychloroquine in patients with early rheumatoid arthritis failing initial methotrexate monotherapy, a Swedish study has shown.
The SWEFOT trial was designed to compare two strategies in patients with early RA who had failed an initial 3-4 months treatment with methotrexate monotherapy. Researchers initially treated 487 patients with early RA, with symptoms for less than one year, with methotrexate (up to 20mg/week).
After three to four months, the 258 patients who had not achieved remission (defined as DAS28 < 3.2) and who were unable to tolerate methotrexate were randomised to DMARD therapy with sulfasalazine plus hydroxychloroquine or to infliximab (3mg/kg/infusion, given at 0, 2, 6 weeks, then every 8 weeks). Patients were allowed to switch therapy once (to cyclosporine in the DMARD group and to etanercept in the anti-TNF group) if they were unable to tolerate their treatment.
Results reported at EULAR showed that just over one-quarter (26%) of patients treated with DMARD therapy achieved a EULAR good response after 12 months, compared to 42% of those treated with infliximab (p
воскресенье, 7 августа 2011 г.
Dieting and exercise improve osteoarthritis
A combination of weight loss and exercise provides functional improvements in overweight patients with osteoarthritis, a new study shows.
Research published in Arthritis and Rheumatism involved 316 older adults with knee osteoarthritis and a BMI of at least 28 who were randomized to receive a dietary intervention, an exercise intervention, both, or usual care. Of these subjects, 252 completed the study.
The exercise programme involved thrice weekly hour-long sessions that focused on aerobics and resistance training.
The dietary intervention incorporated group dynamics theory and social cognitive theory into a staged program with a goal of maintaining an average weight loss of 5% during the 18-month period.
Subjects in the diet-plus-exercise group experienced a significant improvement in self-reported physical function, 6-minute walk distance, stair-climb time, and knee pain.
The diet-only intervention appeared to offer no functional benefits over usual care but patients in the dietary intervention groups lost significantly more weight than those in the usual care group.
"The results of the study are important for clinicians and patients, because they provide evidence for significant, although modest, treatment effects of a dietary weight loss programme combined with regular exercise classes for sedentary, overweight and obese individuals with knee osteoarthritis," Dr. Marlene Fransen, from the University of Sydney in New South Wales, Australia, notes in a related editorial.
Reference: Messier S et al (2004) Exercise and dietary weight loss in overweight and obese older adults with knee osteoarthritis: The arthritis, diet, and activity promotion trial Arthritis Rheum 50 (5) 1501-1510
From: Nursing Times Online
Research published in Arthritis and Rheumatism involved 316 older adults with knee osteoarthritis and a BMI of at least 28 who were randomized to receive a dietary intervention, an exercise intervention, both, or usual care. Of these subjects, 252 completed the study.
The exercise programme involved thrice weekly hour-long sessions that focused on aerobics and resistance training.
The dietary intervention incorporated group dynamics theory and social cognitive theory into a staged program with a goal of maintaining an average weight loss of 5% during the 18-month period.
Subjects in the diet-plus-exercise group experienced a significant improvement in self-reported physical function, 6-minute walk distance, stair-climb time, and knee pain.
The diet-only intervention appeared to offer no functional benefits over usual care but patients in the dietary intervention groups lost significantly more weight than those in the usual care group.
"The results of the study are important for clinicians and patients, because they provide evidence for significant, although modest, treatment effects of a dietary weight loss programme combined with regular exercise classes for sedentary, overweight and obese individuals with knee osteoarthritis," Dr. Marlene Fransen, from the University of Sydney in New South Wales, Australia, notes in a related editorial.
Reference: Messier S et al (2004) Exercise and dietary weight loss in overweight and obese older adults with knee osteoarthritis: The arthritis, diet, and activity promotion trial Arthritis Rheum 50 (5) 1501-1510
From: Nursing Times Online
четверг, 4 августа 2011 г.
Pfizer's Oral JAK-3 Inhibitor Demonstrates Statistically Significant Response For Patients With Rheumatoid Arthritis, New Phase 2 Studies Show
Pfizer announced today that data from two new mid-stage clinical studies of the company's oral JAK-3 inhibitor, CP-690,550, showed statistically significant response versus placebo for patients with rheumatoid arthritis (RA). Data from these two Phase 2 trials and one ongoing open-label safety study are being presented this week at the 10th Annual Congress of the European League Against Rheumatism (EULAR). These results confirm findings from two previously reported Phase 2 studies in RA and have been used to support dose selection for Phase 3.
Dose-Ranging with CP-690,550 Alone
Data presented from a 12-week interim analysis of a six-month, double-blind, placebo-controlled study (Study A3921035), which evaluated 384 patients with active RA who had not responded to a disease-modifying anti-rheumatic drug (DMARD), such as methotrexate, showed that patients treated with 5, 10 and 15 mg twice-daily doses of CP-690,550 experienced statistically significantly superior outcomes compared to placebo.
"This compound could represent a promising advance in rheumatoid arthritis treatment for patients who need an alternative to currently available therapies," said Michael Berelowitz, MD, Senior Vice President Clinical Development and Medical Affairs for Pfizer Specialty Care. "The size of our comprehensive Phase 2 program enabled us to identify doses for advancement into late-stage clinical trials."
The primary endpoint of the study was ACR 20 response rate, which signifies a 20 percent improvement in tender and swollen joint counts as well as other criteria, at Week 12. ACR 20 responses for the 3, 5, 10 and 15 mg twice-daily doses were statistically significantly superior (49.0 percent, 63.3 percent, 75.4 percent, 75.4 percent) versus patients treated with placebo (28.8 percent), and these differences were seen as early as week two. In addition, statistically significantly superior responses were also seen in ACR 50 response rates for the 5, 10 and 15 mg twice daily doses and in the ACR 70 response rates for the 10 and 15 mg twice-daily doses. The study included adalimumab as an active control.
In this study, most commonly-reported treatment-emergent adverse events were urinary tract infections, diarrhea, bronchitis, and headache. All of these adverse events were mild or moderate in severity. Serious adverse events and adverse events leading to discontinuation were infrequent. Significant, dose-dependent decreases in mean neutrophil counts and increases in mean LDL, HDL, total cholesterol and mean serum creatinine were consistent with what had been observed in previous studies of CP-690,550 in RA.
CP-690,550 with Methotrexate in Japanese Patients
In addition, data from a three-month, double-blind, placebo-controlled study (Study A3921039) evaluating 136 Japanese patients whose RA was active despite ongoing treatment with methotrexate demonstrated that patients treated with 1, 3, 5 and 10 mg doses of CP-690,550 in addition to stable background methotrexate experienced statistically significantly superior ACR 20 response rates compared to methotrexate plus placebo. The primary endpoint was ACR 20 response rate at week 12.
All doses (1, 3, 5 and 10 mg) were statistically significantly superior by week 12 (64.3 percent, 77.8 percent, 96.3 percent and 80.8 percent) compared to methotrexate plus placebo (14.3 percent) and these differences were seen as early as week two. In addition, secondary endpoints for the ACR 70 response rates with the 5 mg and 10 mg doses (33.3 percent, 34.6 percent) at week 12 were statistically significantly superior compared to methotrexate plus placebo (3.6 percent).
In this study, most commonly-reported treatment-emergent adverse events were nasopharyngitis, increased liver transaminases, increased blood cholesterol, and stomach discomfort. All of these adverse events were mild or moderate in severity. Serious adverse events and adverse events leading to discontinuation were infrequent. Significant, dose-dependent decreases in mean neutrophil counts and increases in mean LDL, HDL, total cholesterol and mean serum creatinine were consistent with what had been observed in previous studies of CP-690,550 in RA.
Ongoing, Long-term, Open Label Safety Study
Data from an ongoing, long-term, open label safety study (Study A3921024) were also presented. In this interim analysis, CP-690,550 showed a safety profile similar to that observed in previous randomized trials. Most adverse events were mild or moderate. Most frequently reported adverse events (greater than or equal to 1.5 percent) were urinary tract infection, diarrhea, anemia, nausea and sinusitis.
All studies were sponsored by Pfizer Inc.
Phase 3 Program in RA Currently Enrolling Patients
Pfizer's Specialty Care Business Unit initiated a large, global Phase 3 clinical program with CP-690,550 in RA in February 2009 and is exploring the compound as a potential treatment for other autoimmune diseases, including psoriasis and inflammatory bowel disease and for solid organ transplant.
About CP-690,550
CP-690,550 is an oral, selective, potent inhibitor of the JAK family of enzymes, which are involved in numerous inflammatory and autoimmune diseases, including RA. By inhibiting these enzymes, which affect the signaling of multiple cytokines (proteins released by cells to communicate with other cells) that are involved in a broad spectrum of inflammatory and autoimmune diseases, treatment with CP-690,550 may lead to clinically meaningful improvement for patients.
CP-690,550 was invented at Groton labs.
Source
Pfizer
Dose-Ranging with CP-690,550 Alone
Data presented from a 12-week interim analysis of a six-month, double-blind, placebo-controlled study (Study A3921035), which evaluated 384 patients with active RA who had not responded to a disease-modifying anti-rheumatic drug (DMARD), such as methotrexate, showed that patients treated with 5, 10 and 15 mg twice-daily doses of CP-690,550 experienced statistically significantly superior outcomes compared to placebo.
"This compound could represent a promising advance in rheumatoid arthritis treatment for patients who need an alternative to currently available therapies," said Michael Berelowitz, MD, Senior Vice President Clinical Development and Medical Affairs for Pfizer Specialty Care. "The size of our comprehensive Phase 2 program enabled us to identify doses for advancement into late-stage clinical trials."
The primary endpoint of the study was ACR 20 response rate, which signifies a 20 percent improvement in tender and swollen joint counts as well as other criteria, at Week 12. ACR 20 responses for the 3, 5, 10 and 15 mg twice-daily doses were statistically significantly superior (49.0 percent, 63.3 percent, 75.4 percent, 75.4 percent) versus patients treated with placebo (28.8 percent), and these differences were seen as early as week two. In addition, statistically significantly superior responses were also seen in ACR 50 response rates for the 5, 10 and 15 mg twice daily doses and in the ACR 70 response rates for the 10 and 15 mg twice-daily doses. The study included adalimumab as an active control.
In this study, most commonly-reported treatment-emergent adverse events were urinary tract infections, diarrhea, bronchitis, and headache. All of these adverse events were mild or moderate in severity. Serious adverse events and adverse events leading to discontinuation were infrequent. Significant, dose-dependent decreases in mean neutrophil counts and increases in mean LDL, HDL, total cholesterol and mean serum creatinine were consistent with what had been observed in previous studies of CP-690,550 in RA.
CP-690,550 with Methotrexate in Japanese Patients
In addition, data from a three-month, double-blind, placebo-controlled study (Study A3921039) evaluating 136 Japanese patients whose RA was active despite ongoing treatment with methotrexate demonstrated that patients treated with 1, 3, 5 and 10 mg doses of CP-690,550 in addition to stable background methotrexate experienced statistically significantly superior ACR 20 response rates compared to methotrexate plus placebo. The primary endpoint was ACR 20 response rate at week 12.
All doses (1, 3, 5 and 10 mg) were statistically significantly superior by week 12 (64.3 percent, 77.8 percent, 96.3 percent and 80.8 percent) compared to methotrexate plus placebo (14.3 percent) and these differences were seen as early as week two. In addition, secondary endpoints for the ACR 70 response rates with the 5 mg and 10 mg doses (33.3 percent, 34.6 percent) at week 12 were statistically significantly superior compared to methotrexate plus placebo (3.6 percent).
In this study, most commonly-reported treatment-emergent adverse events were nasopharyngitis, increased liver transaminases, increased blood cholesterol, and stomach discomfort. All of these adverse events were mild or moderate in severity. Serious adverse events and adverse events leading to discontinuation were infrequent. Significant, dose-dependent decreases in mean neutrophil counts and increases in mean LDL, HDL, total cholesterol and mean serum creatinine were consistent with what had been observed in previous studies of CP-690,550 in RA.
Ongoing, Long-term, Open Label Safety Study
Data from an ongoing, long-term, open label safety study (Study A3921024) were also presented. In this interim analysis, CP-690,550 showed a safety profile similar to that observed in previous randomized trials. Most adverse events were mild or moderate. Most frequently reported adverse events (greater than or equal to 1.5 percent) were urinary tract infection, diarrhea, anemia, nausea and sinusitis.
All studies were sponsored by Pfizer Inc.
Phase 3 Program in RA Currently Enrolling Patients
Pfizer's Specialty Care Business Unit initiated a large, global Phase 3 clinical program with CP-690,550 in RA in February 2009 and is exploring the compound as a potential treatment for other autoimmune diseases, including psoriasis and inflammatory bowel disease and for solid organ transplant.
About CP-690,550
CP-690,550 is an oral, selective, potent inhibitor of the JAK family of enzymes, which are involved in numerous inflammatory and autoimmune diseases, including RA. By inhibiting these enzymes, which affect the signaling of multiple cytokines (proteins released by cells to communicate with other cells) that are involved in a broad spectrum of inflammatory and autoimmune diseases, treatment with CP-690,550 may lead to clinically meaningful improvement for patients.
CP-690,550 was invented at Groton labs.
Source
Pfizer
понедельник, 1 августа 2011 г.
Efficacy Of Flu Vaccine Drastically Reduced For RA Patients Treated With Rituximab
Rheumatoid arthritis (RA) patients are partially protected by the influenza vaccine 6 - 10 months after treatment with rituximab. Researchers determined that while the flu vaccine is safe, it is ineffective for RA patients in the first 6 months following rituximab treatment. Previous influenza vaccination in rituximab-treated patients does increase pre- and post-vaccination titers, providing some defense to influenza strains. RA activity was not influenced by administration of the flu vaccine. Complete findings of this study are available in the January 2010 issue of Arthritis & Rheumatism, a journal published by Wiley-Blackwell on behalf of the American College of Rheumatology.
RA, a common autoimmune disease, affects 4.6 million individuals worldwide and more than half of those diagnosed are woman, according to a 2000 report on global incidence by the World Health Organization (WHO). Patients with RA are immunocompromised, meaning their immune systems do not function normally, putting them at increased risk of infection. Due to a compromised immune system, doctors advise RA patients to get vaccinated each year against influenza including the new H1N1 virus.
Sander van Assen, M.D. and colleagues from the University Medical Center Groningen in The Netherlands conducted the largest study to date of the effectiveness of the flu vaccine in RA patients using rituximab. Three groups of patients were enrolled in the study: 23 RA patients using rituximab, 20 RA patients taking methotrexate (MTX), and 29 healthy individuals. Those patients taking rituximab were split into two groups with 11 who received the influenza vaccine 4 - 8 weeks after treatment with rituximab (early rituximab subgroup), and 12 individuals who were given the flu shot 6-10 months post-treatment with the drug (late rituximab subgroup). Influenza vaccines were administered intramuscularly between October 2007 and January 2008.
Researchers tested geometric mean titers (GMTs) for each group and found they significantly increased for all influenza strains in the MTX-treated group and in healthy controls, but for none of the influenza strains in the rituximab-treated group. In the late rituximab subgroup, a rise in GMT was noted for the A/H3N2 and seasonal A/H1N1 flu strains indicating some recovery of an immune response 6-10 months after treatment by rituximab. Also less rituximab-treated patients reached levels of antibodies needed for protection against influenza for the A/H3N2 and seasonal A/H1N1 when compared with MTX-treated patients, and for the seasonal A/H1N1 when compared with healthy individuals.
Results further showed that healthy individuals vaccinated the year before showed higher baseline GMT for the A/H3N2 strain than unvaccinated health controls. In the MTX group, higher baseline antibodies were noted for the seasonal A/H1N1 and B strains in previously vaccinated patients compared with unvaccinated subjects. For the Rituximab group, patients previously vaccinated not only had a higher baseline GMT, but also a higher post-vaccination GMT for the seasonal A/H1N1 than patients who were not vaccinated the prior year.
The safety of the flu vaccine was also tested by researchers and found to be safe. There were no differences noted between the 3 groups in the occurrence of side effects from the vaccination. Researchers determined that RA activity was not influenced by the flu vaccine and used the disease activity (DAS28) score prior to vaccination and at 7 and 28 post-vaccination to assess RA activity in patients in the MTX and rituximab groups.
"Individuals who have compromised immune systems, such as with RA, are at risk for complications from contracting the flu virus," said Dr. van Assen. "We recommend yearly influenza vaccination for all RA patients and preemptive vaccination for flu should be considered by those patients who start rituximab treatment."
Source: Wiley - Blackwell
RA, a common autoimmune disease, affects 4.6 million individuals worldwide and more than half of those diagnosed are woman, according to a 2000 report on global incidence by the World Health Organization (WHO). Patients with RA are immunocompromised, meaning their immune systems do not function normally, putting them at increased risk of infection. Due to a compromised immune system, doctors advise RA patients to get vaccinated each year against influenza including the new H1N1 virus.
Sander van Assen, M.D. and colleagues from the University Medical Center Groningen in The Netherlands conducted the largest study to date of the effectiveness of the flu vaccine in RA patients using rituximab. Three groups of patients were enrolled in the study: 23 RA patients using rituximab, 20 RA patients taking methotrexate (MTX), and 29 healthy individuals. Those patients taking rituximab were split into two groups with 11 who received the influenza vaccine 4 - 8 weeks after treatment with rituximab (early rituximab subgroup), and 12 individuals who were given the flu shot 6-10 months post-treatment with the drug (late rituximab subgroup). Influenza vaccines were administered intramuscularly between October 2007 and January 2008.
Researchers tested geometric mean titers (GMTs) for each group and found they significantly increased for all influenza strains in the MTX-treated group and in healthy controls, but for none of the influenza strains in the rituximab-treated group. In the late rituximab subgroup, a rise in GMT was noted for the A/H3N2 and seasonal A/H1N1 flu strains indicating some recovery of an immune response 6-10 months after treatment by rituximab. Also less rituximab-treated patients reached levels of antibodies needed for protection against influenza for the A/H3N2 and seasonal A/H1N1 when compared with MTX-treated patients, and for the seasonal A/H1N1 when compared with healthy individuals.
Results further showed that healthy individuals vaccinated the year before showed higher baseline GMT for the A/H3N2 strain than unvaccinated health controls. In the MTX group, higher baseline antibodies were noted for the seasonal A/H1N1 and B strains in previously vaccinated patients compared with unvaccinated subjects. For the Rituximab group, patients previously vaccinated not only had a higher baseline GMT, but also a higher post-vaccination GMT for the seasonal A/H1N1 than patients who were not vaccinated the prior year.
The safety of the flu vaccine was also tested by researchers and found to be safe. There were no differences noted between the 3 groups in the occurrence of side effects from the vaccination. Researchers determined that RA activity was not influenced by the flu vaccine and used the disease activity (DAS28) score prior to vaccination and at 7 and 28 post-vaccination to assess RA activity in patients in the MTX and rituximab groups.
"Individuals who have compromised immune systems, such as with RA, are at risk for complications from contracting the flu virus," said Dr. van Assen. "We recommend yearly influenza vaccination for all RA patients and preemptive vaccination for flu should be considered by those patients who start rituximab treatment."
Source: Wiley - Blackwell
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