Patients with early rheumatoid arthritis who achieved remission after 1 year of treatment with abatacept and methotrexate had a small but significantly greater rate of sustained remission for another 6 months following withdrawal of all drugs when compared with patients who took methotrexate alone in a randomized phase IIIb study.
The AVERT (Assessing Very Early Rheumatoid Arthritis Treatment) study randomized 351 early rheumatoid arthritis (RA) patients who were methotrexate naive, tested positive for anticitrullinated peptide–2 antibody, and had a 28-joint Disease Activity Score using C-reactive protein (DAS28-CRP) of more than 3.2 to weekly doses of 125 mg abatacept plus methotrexate, abatacept monotherapy, or methotrexate alone. Methotrexate was initiated at 7.5 mg/wk and was then titrated to 15-20 mg/wk in 6-8 weeks, but the protocol allowed for 10 mg or less per week in patients who could not tolerate higher doses.
In one of two primary endpoints, significantly more patients in the combination arm achieved remission (DAS28-CRP <2.6) at 12 months (60.9%), compared with patients who took methotrexate alone (45.2%), for an odds ratio of 2.01 (P = .010). The rate was 42.5% in the abatacept monotherapy arm, Dr. Paul Emery of the Leeds Institute of Rheumatic and Musculoskeletal Medicine at the University of Leeds (England) and his colleagues reported (Ann. Rheum. Dis. 2014 Nov. 3 [doi:10.1136/annrheumdis-2014-206106]).
At the end of the first 12 months, patients who had achieved a DAS28-CRP score of less than 3.2 entered a 12-month treatment withdrawal period. Remission at both 12 and 18 months – the second primary endpoint – occurred in 14.8% of patients on combination therapy and 7.8% of those on methotrexate alone (OR, 2.51; P = .045). A total of 12.4% of abatacept monotherapy patients achieved remission at both 12 and 18 months.
The results suggest that in early RA drug-free remission may be possible following treatment with abatacept, the researchers said.
In the 12-month treatment period, the serious adverse events were reported in 12.1% taking abatacept monotherapy, 6.7% taking combination therapy, and 7.8% taking methotrexate alone.
The study was sponsored by Bristol-Myers Squibb, which manufactures abatacept (Orencia). Dr. Emery reported receiving consulting fees and grant support from Bristol-Myers Squibb as well as other companies that market drugs for RA. Many of his coauthors reported similar disclosures. Two authors are employees of Bristol-Myers Squibb.