MADRID – A 2-year head-to-head comparison of abatacept and adalimumab in rheumatoid arthritis patients who were on background methotrexate has found equal improvement with both biologics, according to results from a study presented at the annual European Congress of Rheumatology.
The randomized, investigator-blinded AMPLE trial is the first 2-year comparator study of biologics done in biologic-naive rheumatoid arthritis patients.
"Through 2 years of treatment, in this first active comparator study between biologic agents in rheumatoid arthritis patients with an inadequate response to methotrexate, this robust data set demonstrates that subcutaneous abatacept and adalimumab were equally efficacious in clinical, functional, and radiographic outcomes," said Dr. Michael H. Schiff, a professor of medicine at the University of Colorado, Denver.
Researchers recruited 646 patients with active RA and an inadequate response to methotrexate, and randomized them to either 125 mg of abatacept weekly (without an IV load) or 40 mg of adalimumab biweekly, with a stable dose of methotrexate.
The data show that both agents have an excellent retention rate, with 79% of the abatacept and 65% of the adalimumab groups completing the 2-year follow-up.
The two medications showed similar efficacy for American College of Rheumatology (ACR) 20, 50, 70, and 90 responses and rates of remission on the Disease Activity Score-28 (DAS28), Dr. Schiff said. For ACR 20, the 2-year response rate was 60% in each group. The ACR 50 response rate was 47% for the adalimumab group and 45% for the abatacept group. For the ACR 70, the rates were 29% for adalimumab and 31% for abatacept, and for the ACR 90, the rates were 8% for adalimumab and 15% for abatacept.
The 2-year DAS28 rate was virtually identical in each group, with a mean decrease of about 2.2 from baseline. X-ray non-progression was seen in 84% of each group at 2 years, Dr. Schiff said.
The study found similar numbers of serious adverse events in both arms (14% of the abatacept group and 17% of the adalimumab group). However, serious adverse events leading to discontinuation of the study medication occurred in 5% of patients taking adalimumab and 2% of those taking abatacept.
Dr. Michael Schiff
There was one death in each group – neither of which was related to the study drugs. There were seven malignancies in each group; four patients in each group discontinued their study medication due to neoplasm.
Infections were the most common serious side effects (31 total), occurring in 4% of the abatacept and 6% of the adalimumab groups). There were eight opportunistic infections – four in each group. The adalimumab group had two cases of pulmonary tuberculosis, one case of disseminated tuberculosis, and one case of disseminated histoplasmosis. There were three cases of pneumonia in the abatacept group and four in the adalimumab group.
Autoimmune events were also relatively common – 18 in all, with 12 in the abatacept group (4%) and 6 in the adalimumab group (2%). Dr. Schiff said none of these were serious or clinically important.
During the question-and-answer period, Dr. Schiff said it’s not currently possible to predict which patients would respond to the drugs. "We looked at responders in both groups and were not able to differentiate them based on clinical characteristics," he said. "We are now analyzing the biomarkers and hope to have that information for EULAR 2014."
"EULAR/ACR guidelines recommend starting a patient on methotrexate and then optimizing the dose over 3-6 months, and if a patient has an incomplete response to methotrexate, then to add a biological agent," said Dr. Schiff in an interview.
He noted that anti-tumor necrosis factor (anti-TNF) agents have been the first choice of most rheumatologists, and adalimumab is the most widely chosen anti-TNF agent worldwide, which is why it was selected as one of the agents for the head-to-head trial. Abatacept employs another method of action: T-cell inhibition.
"This paper has important clinical significance because a patient and his or her rheumatologist want to have data to make an informed choice of a biologic agent to add when an incomplete response to methotrexate occurs," Dr. Schiff said.
Senior writer Michele Sullivan contributed to this report.