ABATACEPT INDUCES SUSTAINED IMPROVEMENTS IN PHYSICAL FUNCTION AND REDUCTIONS IN PAIN OVER 3 YEARS IN RHEUMATOID ARTHRITIS PATIENTS WITH AN INADEQUATE RESPONSE TO METHOTREXATE

A. Russell, J. Kremer , F. Irazoque , Y. Zhou , Z. Ge , T. Li , L. Moreland University of Alberta Hospital, Edmonton, Canada, The Center for Rheumatology, Albany, United States, Centro Medico Nacional, Mexico City, Mexico, Bristol-Myers Squibb, Princeton, University of Alabama at Birmingham School of Medicine, Birmingham, United StatesObjectives: Patients with rheumatoid arthritis (RA) exhibit significant impairments in physical function and high disability levels. The effects of abatacept on physical function were examined in the Phase III AIM (Abatacept in Inadequate responders to Methotrexate [MTX]) trial and in a similar patient population treated with abatacept for 3 years as part of a Phase II trial.Methods: AIM was a 1-year, double-blind, placebo-controlled trial. Also presented are data from a 1-year, double-blind Phase II trial with 2 years of an open-label long-term extension (LTE). Both studies evaluated a fixed dose of abatacept approximating 10 mg/kg with background MTX in patients with active RA despite MTX treatment. Physical function was assessed using the Health Assessment Questionnaire (HAQ) in AIM and the modified HAQ in the Phase II study; both studies included a HAQ responder analysis (proportion of patients demonstrating an improvement of ≥0.3 units, greater than the minimum clinically meaningful improvement [≥0.22 units]). Pain was measured using a 100 mm Visual Analog Scale (VAS).Results: In AIM, 433 and 219 patients were randomized to abatacept and placebo treatment, respectively, with 385 (88.9%) of the abatacept group and 162 (74.0%) of the placebo group completing 1 year. In the Phase II trial, 84 (73%) abatacept-treated patients entered the LTE. In AIM, a significant proportion of abatacept-treated patients demonstrated clinically meaningful improvements in physical function and significant improvements from baseline in HAQ scores and pain versus placebo at 1 year. Similar improvements in the modified HAQ and pain were sustained through 3 years in the Phase II study (Table). Abatacept was generally safe and well tolerated in these patients. Table Assessment AIM trial Phase II* 6 mo 1 yr 1 yr† 2 yrs 3 yrs Abatacept Placebo Abatacept Placebo Abatacept Abatacept Abatacept HAQ % (SE) improvement 35.2 (1.9)‡ 20.9 (2.7) 37.3 (2.3)‡ 19.6 (3.2) 49.4 (4.3) 46.3 (5.5) 49.3 (5.3) HAQ response (n [%]) 259 (61.1)‡ 97 (45.3) 270 (63.7)‡ 84 (39.3) 46/84 (54.8) 39/73 (53.4) 34/64 (53.1) Pain: % (SE) improvement 42.5 (5.3)‡ 3.5 (7.4) 50.5 (4.0)‡ 8.0 (5.7) 52.4 (5.7) 50.2 (6.6) 55.6 (5.3) *As observed; †Blinded, placebo-controlled phase; ‡p<0.001 vs. placebo *As observed; †Blinded, placebo-controlled phase; ‡p<0.001 vs. placeboConclusion: The selective co-stimulation modulator, abatacept, has previously demonstrated robust clinical efficacy in patients with an inadequate response to MTX. Here, abatacept demonstrated significant and clinically meaningful improvements in physical function as well as reductions in pain; similar improvements were sustained through 3 years in the Phase II study. These data suggest abatacept treatment has the potential to provide real-life benefits to patients with RA.References: 1 Kremer JM et al. New Engl J Med 2003; 349(20): 1907–1915Citation: Ann Rheum Dis, volume 64, supplement III, year 2005, page 402Session: Health services, economics and outcome research 1