Abatacept achieved an efficacy similar to that of adalimumab in the treatment of rheumatoid arthritis with a comparable safety profile in a 2-year, head-to-head randomized trial.
The multinational phase IIIb study established the noninferiority of abatacept as compared with the commonly used adalimumab. Both agents are targeted biologic disease-modifying antirheumatic drugs (bDMARDs), but with different mechanisms of action: Adalimumab is a tumor necrosis factor inhibitor, whereas abatacept is a T-cell costimulation modulator.
Dr. Michael E. Weinblatt of Brigham and Women’s Hospital in Boston and his associates conducted a intent-to-treat analysis of the two drugs, administered along with a stable dosage of methotrexate (MTX), in 646 patients who had confirmed diagnoses of rheumatoid arthritis for less than 2 years and had an inadequate response to MTX alone (Arthritis Rheum. 2013;65:28-38 [doi: 10.1002/art.37711]).
Dr. Michael E. Weinblatt
The patients had not received previous bDMARD therapy; and all had active disease with a score of at least 3.2 on the Disease Activity Score in 28 joints using the C-reactive protein level (DAS28-CRP). They were stratified according to whether they had moderate disease (a DAS28-CRP score of 3.2-5.1) or severe disease (greater than 5.1), with approximately equal distribution of disease severity levels in both treatment groups.
A total of 318 patients received 125 mg of subcutaneous abatacept once a week, and 328 patients received 40 mg of subcutaneous adalimumab once every other week. Both groups received stable doses of MTX at 15-25 mg per week (except for those who received 7.5 mg or more if they had a documented intolerance to higher dosages). Patients could not take any other DMARDs during the trial but could receive either hydroxychloroquine or sulfasalazine, as well as low-dose oral corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs), and up to two courses of high-dose corticosteroids.
Patients could not be blinded to the treatments for logistical reasons, but clinical assessors of their treatment, adverse events, and disease severity were blinded. The 13.8% of abatacept patients and 18% of adalimumab patients who discontinued therapy were considered nonresponders at all visits after they discontinued the study.
The researchers used the American College of Rheumatology 20% improvement response (ACR20) at 1 year as the primary outcome. ACR20 improvement criteria include at least a 20% reduction in the number of tender joints (out of 68) and swollen joints (out of 66), as well as three of five other attributes related to the patient’s pain, the patient’s or doctor’s disease assessment, or the C-reactive protein levels.
At 1 year, 64.8% of patients in the abatacept group (95% confidence interval, 59.5%-70.0%) and 63.4% of patients in the adalimumab group (95% CI, 58.2%-68.6%) achieved an ACR20 response. The researchers estimated the difference between the two groups’ ACR20 response rates to be 1.8% (95% CI, –5.6% to 9.2%).
Secondary outcomes of ACR50 and ACR70 were also reported at 1 year: 46.2% of abatacept patients and 46% of adalimumab patients achieved an ACR50 response. Meanwhile, 29.2% of abatacept patients and 26.2% of adalimumab patients achieved an ACR70 response. The adjusted mean improvement in the DAS28-CRP score at 1 year was –2.30 for the abatacept patients and –2.27 for the adalimumab patients. Using an ACR/European League Against Rheumatism definition, the remission rate among abatacept patients was 13.5%, compared with 15.7% among adalimumab patients.
Safety profiles were similar in both groups, except that more adalimumab patients reported local injection site reactions (9.1%) and injection pain (2.4%) than did abatacept patients (3.8% and 0%, respectively). Overall, the serious adverse event (SAE) rate was 10.1% in the abatacept group and 9.1% in the adalimumab group; related SAEs were 2.5% in the abatacept group and 3.4% in the adalimumab group.
Small percentages of participants discontinued the study because of adverse events: 1.3% of patients taking abatacept and 3% of patients taking adalimumab, while 3.5% of the patients on abatacept and 6.1% of patients on adalimumab discontinued because of non-SAEs.
The researchers concluded that both drugs are of "comparable clinical benefit, suggesting that these two agents should be considered equally for the treatment of rheumatoid arthritis patients who have an inadequate response to MTX."
The study was funded by Bristol-Myers Squibb, which manufactures abatacept. All eight authors have past or present financial relationships, including research grants, consulting fees, and/or stock ownership (two authors) in Bristol-Myers Squibb. Most have financial relationships with Abbott and multiple other pharmaceutical companies.