Bristol-Myers Squibb Company (NYSE: BMY) today announced the results of AMPLE (Abatacept Versus Adalimumab Comparison in Biologic-Naïve rheumatoid arthritis (RA) Subjects With Background Methotrexate), a head-to-head clinical trial of 646 patients comparing the subcutaneous (SC) formulation of ORENCIA® (abatacept) vs. Humira® (adalimumab), each on a background of methotrexate (MTX), in biologic naïve patients with moderate to severe RA. AMPLE met its primary endpoint (as measured by non-inferiority) and demonstrated that ORENCIA plus MTX achieved comparable rates of efficacy for the American College of Rheumatology criteria of 20 percent (ACR20) response at 1 year of 64.8% vs. 63.4% Humira plus MTX.
ACR50, 70 and major clinical response (ACR70 for 6 consecutive months), considered to be more stringent measures of efficacy, as well as DAS-28-CRP, were also assessed at 1 year and found to be generally comparable for the two arms. Kinetics of response and inhibition of radiographic progression were generally comparable for the two groups over a 12-month period. Injection-site reactions (a key secondary endpoint) were statistically significantly fewer in the ORENCIA plus MTX group. Discontinuations due to adverse events were 3.5% for ORENCIA plus MTX compared to 6.1% for Humira plus MTX while discontinuations due to serious adverse events were 1.3% for ORENCIA plus MTX compared to 3% for Humira plus MTX. Autoimmune events (mild to moderate in severity) reported in the ORENCIA SC plus MTX group was 3.1% and 1.2% in the Humira plus MTX group. Other safety outcomes were similar at 12 months. The results of AMPLE were presented today at the European League Against Rheumatism (EULAR) Annual European Congress of Rheumatology.
"Results from AMPLE provide important information comparing the efficacy of ORENCIA SC to Humira, including kinetics of response," said Michael Schiff, M.D., M.A.C.R., University of Colorado, and principal AMPLE study investigator. "The results demonstrate comparability between two agents for the primary endpoint of ACR20 and provides relevant data on ACR50 and 70."
"AMPLE is the first head-to-head study between two biologics which incorporates radiographic progression endpoints and provides important data on erosions and joint space narrowing in patients using ORENCIA SC and Humira, both on a background of methotrexate," said Désirée van der Heijde, M.D. Ph.D., Professor of Rheumatology, Leiden University Medical Center.
About the Study
AMPLE is a phase IIIb randomized, investigator-blinded multinational study of 24 months duration with a 12 month efficacy primary endpoint (non-inferiority for ACR20). The study included 646 adult biologic-naïve patients with active moderate to severe RA and inadequate response to MTX; 318 in the ORENCIA SC® (abatacept) plus MTX group and 328 in the Humira plus MTX group. Patients were stratified by disease activity and randomized to either 125 mg ORENCIA SC weekly (without an IV load) or 40 mg Humira every other week, both on background MTX. The primary endpoint was to determine non-inferiority of ORENCIA SC plus MTX to Humira plus MTX by a difference in ACR20 response at 12 months. Secondary endpoints included injection site reactions, radiographic non-progression as assessed using the van der Heijde modified total Sharp score (mTSS) method, safety and retention.
About ORENCIA
ORENCIA SC and IV is indicated for reducing signs and symptoms, inducing major clinical response, inhibiting the progression of structural damage, and improving physical function in adult patients with moderately to severely active rheumatoid arthritis. ORENCIA may be used as monotherapy or concomitantly with disease-modifying antirheumatic drugs (DMARDs) other than tumor necrosis factor (TNF) antagonists.
ORENCIA IV is indicated for reducing signs and symptoms in pediatric patients 6 years of age and older with moderately to severely active polyarticular juvenile idiopathic arthritis. ORENCIA IV may be used as monotherapy or concomitantly with methotrexate (MTX). ORENCIA SC has not been studied in pediatric patients. ORENCIA should not be administered concomitantly with TNF antagonists.
ORENCIA is not recommended for use concomitantly with other biologic rheumatoid arthritis (RA) therapy, such as anakinra.
ORENCIA is intended for use under the guidance of a physician or healthcare practitioner.
About Rheumatoid Arthritis
Rheumatoid arthritis (RA) is a systemic, chronic, autoimmune disease characterized by inflammation in the lining of joints (or synovium), causing joint damage with chronic pain, stiffness, swelling and fatigue. RA causes limited range of motion and decreased joint function. The condition is more common in women than in men, who account for 75% of patients diagnosed with RA.
About Bristol-Myers Squibb
Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases.