Bristol-Myers Squibb Company announced the results of three post-hoc analyses from two phase III pivotal trials that showed Orencia (abatacept) improved daily activity participation, such as work or household chores, physical and social-role independence and sleep quality in adult rheumatoid arthritis (RA) patients who have had an inadequate response to one or more disease-modifying anti-rheumatic drugs (DMARDs), such as methotrexate (MTX) or tumour necrosis factor (TNF) antagonists.
These data are from post-hoc analyses of two phase III pivotal trials investigating Orencia: AIM (Abatacept in Inadequate responders to Methotrexate) and Attain (Abatacept Trial in Treatment of Anti-TNF Inadequate Responders).
"The chronic nature of RA can have a significant impact on a person's health-related quality of life, including independence, ability to perform daily activities and sleep quality," said George Wells, M.Sc., Ph.D., Professor of the Department of Epidemiology and Community Medicine, University of Ottawa.
AIM was a phase III multi-centre, randomised, double-blind, placebo- controlled trial with 652 patients treated at baseline who had active RA despite MTX therapy (638 included in efficacy analyses). The study was double-blind through one year, followed by an ongoing, open-label, long-term extension study. A total of 376 (from the original 424) patients in the group treated with Orencia (abatacept) entered the long-term extension study. Additional DMARDs, non-steroidal anti-inflammatory drugs (NSAIDs), and aspirin were added and/or adjusted at the discretion of the investigator in the long- term extension study. Primary reasons for discontinuation in the long-term extension studies were adverse events, withdrawal of consent, and lack of efficacy.
Primary endpoints were ACR 20 at six months Orencia vs. placebo (67.9 per cent vs. 39.7 per cent, respectively; p-value less than 0.001), clinically significant improvement in HAQ-DI at one year (63.7 per cent vs. 39.3 per cent, respectively; p-value less than 0.001), erosion score at one year (mean change from baseline 0.61 vs. 1.47, respectively; p-value less than 0.01). Secondary endpoints included ACR 20, 50, and 70 over time, major clinical response (45 per cent for Orencia plus MTX), DAS at one year (42.5 per cent vs. 9.9 per cent, respectively; p-value less than 0.001), joint space narrowing (mean change from baseline 0.46 vs. 0.97, respectively; p-value less than 0.01), total Sharp scores at one year (mean change from baseline 1.07 vs. 2.43, respectively; p-value less than 0.01), and SF-36 through one year (mean change from baseline 8.44 vs. 5.28, respectively; p-value less than 0.001).
ATTAIN was a phase III multi-centre, randomised, double-blind, placebo-controlled trial with 391 patients treated at baseline who had active RA despite anti-TNF therapy (389 included in efficacy analyses). The study was double-blind through six months, followed by an ongoing, open-label, long- term extension study. A total of 217 (from the original 256) patients in the group treated with Orencia entered the long-term extensions study. Additional DMARDs, NSAIDs, and aspirin were added and/or adjusted at the discretion of the investigator in the long-term extension study. Primary reasons for discontinuation in the long-term extension studies were adverse events and lack of efficacy
Primary endpoints were ACR 20 at six months Orencia vs. placebo (50.4 placebo vs. 19.5 per cent, respectively; p-value less than 0.001) and improvement in HAQ-DI at six months (47.3 per cent vs. 23.3 per cent, respectively; p-value less than 0.001). Secondary endpoints were ACR 20, 50, and 70 over time, DAS28 at six months (DAS28 less than or equal to 3.2, 18 per cent and DAS28 less than 2.6; 11.1 per cent) and SF-36 at six months (55.6 per cent vs. 31.6 per cent, respectively; p-value less than 0.001). In five clinical trials, the most serious adverse reactions were serious infections (3 per cent Orencia (abatacept) vs. 1.9 per cent placebo) and malignancies (1.3 per cent Orencia vs. 1.1 per cent placebo). The most commonly reported acute infusion-related AEs (one to two per cent) were dizziness, headache, and hypertension with fewer than one per cent of patients discontinuing Orencia due to infusion-related events.
Orencia is indicated in the United States for reducing signs and symptoms, inducing major clinical response, inhibiting the progression of structural damage, and improving physical function in adults with moderately to severely active rheumatoid arthritis who have had an inadequate response to one or more DMARDs, such as methotrexate or TNF antagonists. Orencia may be used as monotherapy or concomitantly with DMARDs other than TNF antagonists. Orencia should not be administered concomitantly with TNF antagonists and is not recommended for use concomitantly with anakinra.
Orencia is administered by a healthcare professional as a 30-minute intravenous infusion at a fixed dose based on body weight range approximating 10 mg/kg at day 0, 2 weeks, 4 weeks, and every 4 weeks thereafter. Acute infusion-related reactions were experienced in nine per cent of people treated with Orencia and in six per cent of people treated with placebo. According to the full prescribing information, the most frequently reported infusion- related adverse events (1 per cent to 2 per cent) were dizziness, headache, and hypertension. In pivotal studies, pre-medications were not required. However, appropriate medical support measures for the treatment of hypersensitivity reactions should be available for immediate use in the event of a reaction, the company said.
Bristol-Myers Squibb Company is a global pharmaceutical and related health care products company whose mission is to extend and enhance human life.