ABATACEPT LEADS TO SIGNIFICANT IMPROVEMENTS IN ALL AMERICAN COLLEGE OF RHEUMATOLOGY CORE COMPONENTS IN PATIENTS WITH AN INADEQUATE RESPONSE TO ANTI-TNF THERAPY IN THE ATTAIN TRIAL

M. Schiff, M. Dougados , M. Luggen , L. Espinoza , I. Nuamah , R. Aranda , J. Becker , M. Genovese Denver Arthritis Clinic, Denver, United States, Rene Descartes University, Service de Rhumatologie B, Paris, France, University of Cincinnati Medical Center, Cincinnati, Louisiana State University Health Sciences Center, School Of Medicine, New Orleans, Bristol-Myers Squibb, Princeton, Stanford University Medical Center, Stanford, United StatesObjectives: There are currently no clinically proven treatment options for rheumatoid arthritis (RA) patients with inadequate responses to anti-TNF-alpha therapy. Abatacept has previously shown efficacy in patients with an inadequate response to methotrexate. The effect of abatacept on the ACR core components was assessed in patients with active RA with inadequate responses to anti-TNF-alpha therapy as part of the ATTAIN (Abatacept Trial in Treatment of Anti-TNF INadequate responders) trial.Methods: ATTAIN was a 6-month, randomized, double-blind, placebo-controlled, multicenter, Phase III trial of a fixed dose of abatacept approximating 10 mg/kg vs. placebo in patients with active RA who were not responding adequately to >3 months of anti-TNF-alpha therapy (etanercept and/or infliximab). Randomized patients had discontinued all anti-TNF-alpha therapy due to a lack of efficacy. Study medication was administered on Days 1, 15, 29 and then every 28 days thereafter by intravenous infusion. All patients received ≥1 background DMARD (abatacept vs. placebo: MTX, 75.6 vs. 82.0%; anakinra, 2.7 vs. 2.3%; all other non-biologic DMARDs were <10% in each group). Data are presented for all randomized and treated patients.Results: A total of 391 patients were randomized to receive abatacept or placebo in a 2:1 ratio. Baseline characteristics were similar between treatment groups. At 3 months and 6 months, respectively, an ACR 20 response was achieved by 46.1 and 50.4% of abatacept- vs. 18.0 and 19.5% of placebo-treated patients (p<0.001). Significant improvements were also observed in ACR components in the abatacept vs. placebo groups at 6 months (Table). From Day 15 onwards, following the first dose, statistically significant improvements were observed in tender joints (p<0.001), patients'' and physicians'' global assessment (p<0.01) and C-reactive protein (CRP; p<0.01), in the abatacept vs. placebo groups (data not shown). At 6 months, CRP in the placebo group was elevated from baseline. Abatacept was generally safe and well tolerated in these patients. Mean % improvement from baseline in ACR component 6 months* Abatacept + DMARDs Placebo + DMARDs (n=256) (n=133) Tender joint count 47.8 20.0 Swollen joint count 44.3 23.8 Patient-reported pain 28.6 4.4 Patient global assessment 30.9 4.5 Physician global assessment 45.2 21.3 Patient assessed disability (HAQ) 25.5 5.1 CRP 25.1 -28.4 *Last observation carried forward analysis; †p<0.01, ‡p<0.001, both vs. placebo *Last observation carried forward analysis; †p<0.01, ‡p<0.001, both vs. placeboConclusion: In patients with an inadequate response to anti-TNF-alpha therapy, abatacept leads to significant and sustained improvements in each ACR core component. Significant improvements were observed as early as Day 15, following the first dose of abatacept. Furthermore, at 6 months, 50.4% of patients achieved an ACR 20 response. These data support the use of abatacept in patients with an inadequate response to anti-TNF-alpha therapy.References: 1. Kremer JM et al. N Engl J Med 2003; 349(20): 1907–1915Citation: Ann Rheum Dis, volume 64, supplement III, year 2005, page 435Session: Rheumatoid Arthritis – Treatment