Sustaining Remission After RA Therapy Ends

Evaluating Drug-Free Remission With Abatacept in Early Rheumatoid Arthritis: Results From the Phase 3b, Multicenter, Randomised, Active-Controlled AVERT Study of 24 Months, With a 12-Month, Double-Blind Treatment Period

Emery P, Burmester GR, Bykerk VP, et al
Ann Rheum Dis. 2015;74:19-26

Study Summary

The Assessing Very Early Rheumatoid Arthritis Treatment (AVERT) study evaluated the efficacy and safety of three treatments in patients with early anti-citrullinated protein antibody (ACPA)-positive rheumatoid arthritis (RA), defined as ≤ 2 years of persistent inflammatory symptoms. In total, 351 patients were randomly assigned to receive either abatacept plus methotrexate (ABA/MTX; n = 119), methotrexate monotherapy (MTX; n = 116), or abatacept monotherapy (ABA; n = 116). Patients who reached remission, as defined by a C-reactive protein-based Disease Activity Score (DAS)-28 score < 2.6 at 12 months, could have all therapy withdrawn (ABA immediately, and MTX and any corticosteroids over 1 month) and were then followed to determine whether remission was sustained.

At the 12-month mark, remission rates by DAS-28 criteria were ~61% in the ABA/MTX arm, ~46% in the MTX arm, and ~43% in the ABA arm, with the differences between ABA/MTX and MTX reaching statistical significance (P=.01).

Across all patients, at 18 months, there was a higher rate of DAS-28–defined remission in the ABA/MTX arm than in the MTX arm (~15% vs ~8%; P=.045). In addition, within the subset of patients who had therapy withdrawn at 12 months, 18 of 73 (~25%) in the ABA/MTX arm were still in DAS remission at 18 months, compared with 9 of 53 (~17%) in the MTX arm and 15 of 50 (~28%) in the ABA arm. These differences were not statistically significant.

Viewpoint

The AVERT study joins a growing number of trials that assess treatment responses in early RA. This trial is unique in that all patients were ACPA-positive, and a majority (~94%) were also rheumatoid factor-positive. Remission in these patients is therefore particularly meaningful, given that these cases probably represent the most immunologically active form of RA.

Another exciting feature of the study was therapy cessation in those who had reached DAS-28 remission at 12 months. This allowed the investigators to identify that remission is sustained in some patients at 18 months after therapy was withdrawn.

Remission after drug withdrawal did not dramatically differ across the treatment arms, and the chosen study duration is still too short to know how such approaches will affect the course of RA over a patient's lifetime. However, these findings should spur additional studies that shape how we care for patients with RA in the near future.

Abstract