Study Results Supportive of Switching Directly to ORENCIA® From
Barcelona (ots)
Anti-Tumor Necrosis Factor (TNF) Therapy in Inadequately Responding Rheumatoid Arthritis Patients
According to a new study, it is possible to safely switch directly to ORENCIA® from anti-TNF therapy in rheumatoid arthritis patients who have had an inadequate response to anti-TNF therapy. The results were announced today by Bristol-Myers Squibb Company (NYSE: BMY).
Waiting for an ineffective medicine to clear first before trying another therapy like Orencia could subject a rheumatoid arthritis patient to additional pain and discomfort.
ORENCIA®, in combination with methotrexate (MTX) is indicated for the treatment of moderate to severe active rheumatoid arthritis in adult patients who have had an insufficient response or intolerance to other disease-modifying anti-rheumatic drugs (DMARDs) including at least one anti-TNF inhibitor. A reduction in the progression of joint damage and improvement of physical function has been demonstrated with combination treatment with ORENCIA(R) and MTX. ORENCIA® is not approved for use in combination with anti-TNF inhibitors.
"The new data help answer a practical question about whether a direct switch from an anti-TNF therapy to Orencia without a washout period is an option in clinical practice for patients suffering from rheumatoid arthritis," said Maxime Dougados, M.D., Professor of Rheumatology, Universite Rene Descartes, Paris. "Rheumatoid arthritis patients who do not adequately respond to currently available therapies may benefit from Orencia. Because a prior clinical study(1) was conducted with a washout period prior to initiation of Orencia therapy, it is important to know whether we can move directly to Orencia rather than waiting for the non-effective medicine to clear out. These data support that it is safe to switch directly from anti-TNF therapy to Orencia therapy as warranted by patient response."
The study, which was presented at the 8th Annual European Congress of Rheumatology (EULAR), evaluated the safety profile of ORENCIA® in patients with rheumatoid arthritis on background non-biologic disease-modifying anti-rheumatic drugs (DMARDs) who had an inadequate response to anti-TNF therapy.
The ARRIVE (Abatacept Researched in Rheumatoid Arthritis Patients with an Inadequate anti-TNF response to Validate Effectiveness) study was a 6-month open label study that was initiated to determine the safety, tolerability and efficacy profile of ORENCIA® in a clinical practice setting. The primary objective of the ARRIVE study was to summarize the incidence of adverse events, serious adverse events and discontinuations due to adverse events during 6 months of combined treatment with ORENCIA® and one or more of the background non-biologic DMARDs in patients with active RA when one group of anti-TNF inadequate responders were switched to ORENCIA® without a washout period.
Anti-TNF inadequate response was defined as inadequate response due to efficacy according to the investigator's opinion after at least 3 months' use or inadequate response due to safety or tolerability at any time point after patients have received their first dose of anti-TNF therapy.
In an analysis of the ARRIVE study, 842 US patients were treated and evaluated for safety. Of those studied, 370 patients were considered to be "prior" users, which meant they had discontinued anti-TNF therapy at least two months before screening due to a lack of clinical response or an inadequate response and persistent disease activity. The other 472 patients were considered "current" users as they had received anti-TNF therapy within two months of screening, without a clinical response or had an insignificant response and a persistent disease activity score (DAS28) of more than 5.6. All current users started ORENCIA® at their next scheduled anti-TNF dose. Patients received a fixed dose of ORENCIA® (approximately10 milligrams per kilogram of body weight) on Days 1, 15 and 29, and every 4 weeks thereafter, plus stable background DMARD therapy.
Overall, baseline characteristics were similar in both groups (mean DAS28 of 6.2). Mean disease duration was 12.7 and 10.4 years in prior and current users, respectively.
At 6 months, the frequency of adverse events (AEs), serious AEs (SAEs), discontinuations due to AEs/SAEs, infections, neoplasms and deaths were similar in prior and current users.
Events (Days 1-169) "Prior" users "Current" users Overall
(n=%) ORENCIA + DMARDs ORENCIA + ORENCIA +
(n=370) DMARDs (n=472) DMARDs (n=842)
Deaths 1 (0.3) 0 1 (0.1)
SAEs 34 (9.2) 36 (7.6) 70 (8.3)
Discontinuations 8 (2.2) 4 (0.8) 12 (1.4)
due to SAEs
AEs 284 (76.8) 363 (76.9) 647 (76.8)
Discontinuations 15 (4.1) 19 (4.0) 34 (4.0)
due to AEs
Infections 149 (40.3) 181 (38.3) 330 (39.2)
Serious infections 8 (2.2) 11 (2.3) 19 (2.3)
Neoplasms 3 (0.8) 2 (0.4) 5 (0.6)Serious infections also were similar in frequency in prior vs. current users (2.2 vs. 2.3%, respectively); the most frequent being pneumonia (in 0.8% of current pts) and lobar pneumonia (in 0.5% of prior pts). No serious opportunistic infections, including tuberculosis, occurred in either group.
About Orencia
ORENCIA® is a novel medicine as the first and only selective co-stimulation modulator of T-cell activation. ORENCIA® is the first biologic discovered and developed in Bristol-Myers Squibb research centers and was approved in May 2007 by the European Commission.
Medicinal products, including ORENCIA®, which affect the immune system, may affect host defenses against infections and malignancies. Serious infections at least possibly related to treatment were reported in 1.8% of patients with ORENCIA® and in 1.0% of patients not treated by ORENCIA® (receiving placebo). There is a need to evaluate and monitor the patients regarding the risk of infection prior to and during treatment. In the placebo-controlled clinical trials, the frequency of malignancies with ORENCIA(R) was 1.4% and with placebo 1.1%. These rates are similar to that observed in the general rheumatoid arthritis population.(2)
ORENCIA® is contraindicated in patients with severe and uncontrolled infections such as sepsis and opportunistic infections and in patients with hypersensitivity to the active substance or to any of the excipients. Allergic reactions have been reported uncommonly with ORENCIA® in clinical trials, where patients were not required to be pretreated to prevent allergic reactions. In the case of any serious allergic/anaphylactic reaction, ORENCIA® should be discontinued.
About Rheumatoid Arthritis
Rheumatoid arthritis is a systemic, chronic, autoimmune disease characterized by inflammation in the lining of joints (or synovium), causing joint damage with chronic pain, stiffness and swelling. RA causes limited range of motion and decreased function as a result of affected joints losing their shape and alignment. RA may affect up to 4.5 million people in the European Union.(3),(4)
Bristol-Myers Squibb is a global pharmaceutical and related health care products
company whose mission is to extend and enhance human life. ORENCIA® (abatacept) is a trademark of Bristol-Myers Squibb Company.
For information for ORENCIA®, please consult the Summary of Product Characteristics.
(1) Genovese MC, Becker J-C, Schiff M, et al. Abatacept for rheumatoid arthritis refractory to tumor necrosis factor α inhibition, N Engl J Med. 2005;353:1114-1123.
(2) Simon T, poster presentation at EULAR 2006.
(3) http://epp.eurostat.ec.europa.eu/cache/ITY_OFFPUB/KS-SF-07-041 /EN/KS-SF-07-04 1-EN.PDF accessed 25-04-07.
(4) http://ec.europa.eu/health/ph_information/dissemination/diseas es/musculo_en.h tm accessed 25-04-07.
Contact:
Brian Henry
Bristol-Myers Squibb
Office: +33-1-58-83-69-38
Mobile: +33-6-75-09-08-99
E-Mail: brian.henry@bms.com