WASHINGTON, DC — Abatacept and adalimumab had comparable efficacy after 1 year of treatment in patients with rheumatoid arthritis (RA) on background methotrexate therapy. This is the first fully powered study to compare 2 different biologics in the treatment of RA patients on background methotrexate.
"Subcutaneous abatacept was comparable to adalimumab according to most efficacy measures, including radiographic progression. Safety of the 2 drugs was generally similar, with fewer discontinuations and injection site reactions observed with abatacept," stated lead author, Michael Weinblatt, MD, Brigham and Women's Hospital, Boston, Massachusetts.
The AMPLE study is an ongoing, phase 3b, randomized, investigator-blinded study of 24 months duration with a 12-month primary efficacy endpoint, which was reported here at the American College of Rheumatology 2012 annual meeting. A total of 646 biologic-naïve RA patients were randomized 1:1 to abatacept 125 mg weekly or adalimumab 40 mg biweekly; 86.2% and 82%, respectively, completed 12 months of therapy.
Inclusion criteria included active RA of < 5 years duration and inadequate response to methotrexate. All patients were biologic-naïve. Demographic and disease characteristics were well balanced between the 2 treatment arms. Mean Disease Activity Score (DAS28) was 5.5 and mean duration of RA was about 1.8 years.
"Investigators were blinded, the clinical assessor was blinded but the patients were not blinded to the treatment they were receiving," Dr. Weinblatt said. This was done because the 2 treatments are given by different routes of administration and on different schedules and it would have been too cumbersome and inconvenient.
At 1 year, the primary endpoint of at least a 20% improvement in the signs and symptoms of RA as shown by ACR20 was achieved in 64.8% of abatacept-treated patients vs 63.4% of the adalimumab group. "This 1.8% difference in treatment arms showed non-inferiority by a priori definition," Dr. Weinblatt told listeners.
The kinetics of response across ACR20/50/70 was comparable. The rate of ACR50 response was 46.2% and 46%, respectively; ACR70 was achieved in 29.2% and 26.2%, respectively, at 1 year.
The rates of nonradiographic disease progression were also comparable. 85% for abatacept vs 89% for adalimumab.
The 2 treatment arms had similar rates of adverse events, including serious adverse events, which were reported in 20 abatacept-treated patients vs 11 in the adalimumab group. The rate of serious infections was comparable as well, with 7 reported in the abatacept group vs 9 in the adalimumab group. None of these infections led to discontinuations of abatacept, whereas treatment was stopped in 5 of 9 patients taking adalimumab who had serious infections.
The rate of injection site reactions was 3.8% on abatacept vs 9.1% on adalimumab (P = .006).
During the discussion following this presentation, David Felson, MD, Professor of Medicine and Epidemiology at Boston University School of Medicine, Massachusetts, commended the AMPLE investigators for conducting this study. "This is a pioneering effort. Faced with a growing armamentarium of biologic therapies for RA, we need many more of these studies."
Dr. Felson said that the ACR hybrid would be a better measure to use in these comparative studies because it is continuous, whereas ACR20 measures an individual time point. Dr. Weinblatt's response was that the investigators are planning a post-hoc analysis of the AMPLE data using the ACR hybrid.
"European agencies have recommended head-to-head trials. We will need more head-to-head trials of new therapies. Sponsors and payers should appreciate that," Dr. Felson said.
Dr. Weinblatt disclosed financial ties with Bristol-Myers Squibb and Abbott. Dr. Felson has disclosed no relevant relationships; he does receive funding from the National Institutes of Health.
2012 Annual Meeting of the American College of Rheumatology. Abstract 2449. Presented November 12, 2012.
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Cite this: RA Treated With Abatacept Comparable to Adalimumab - Medscape - Nov 16, 2012.