Background Achieving clinical remission and low disease activity (LDA) in early rheumatoid arthritis (RA) limits joint damage and disability.1 Biologics such as anti-TNF agents have been shown to rapidly induce remission in early RA, which may improve the likelihood of long-term treatment success.2 Current EULAR guidelines suggest consideration of biologic withdrawal after achievement of a good clinical state,1 but few studies have explored which patients are the best candidates for therapy reduction or withdrawal.
Objectives To examine the influence of demographic and disease characteristics and early treatment response on the achievement of sustained remission in patients with early RA in the PRIZE study.
Methods Methotrexate (MTX)-/biologic-naïve patients with early moderate-severe RA who achieved DAS28 ≤3.2 at week 39 and <2.6 at week 52 after open-label treatment with etanercept (ETN) 50 mg+MTX 10-25 mg (Phase 1 [P1]) were randomized to ETN 25 mg+MTX, MTX alone, or placebo (PBO) for 39 week in the double-blind phase (Phase 2 [P2]). Mantel-Haenszel chi-square tests were used to analyze the association between baseline (BL) characteristics and P1 treatment responses and P2 sustained remission (ie, DAS28 <2.6 at week 76 and 91, without corticosteroids for week 52-64).
Results Predictors of sustained remission in P2 in the ETN 25 mg+MTX group were: achieving DAS28 sustained remission over weeks 13-52 (vs patients without this P1 response: 79% vs 54%; P=0.044); DAS28 LDA over weeks 13-52 (76% vs 41%; P=0.007); and ACR/EULAR Boolean remission at week 52 (71% vs 44%; P=0.049). Rapid and robust responses in P1 (ie, first DAS28 remission in days 0-179, mean DAS28 ≤1.91 at week 52) were associated with sustained remission in the ETN 25 mg+MTX group in P2 (table). In the MTX group, predictors of P2 sustained remission were achieving DAS28 LDA over weeks 13-52 (49% vs 23%; P=0.044), younger age at BL, and lower levels of C-reactive protein (CRP) at week 52. In the PBO group, predictors were being seronegative at baseline for anticyclic citrullinated peptide (seronegative vs seropositive: 48% vs 11%; P=0.001) and for rheumatoid factor (41% vs 11%; P=0.005) antibodies.
Conclusions Early onset of response to induction therapy with etanercept plus MTX predicted sustained remission with a reduced-dose combination maintenance regimen. These findings are clinically relevant as prompt recognition of patients unlikely to achieve response targets may allow for more timely adjustments in treatment and ultimately better long-term outcomes.
Smolen JS, et al. Ann Rheum Dis 2010;69:964-75.
Emery P, et al. Ann Rheum Dis 2012;71:989-92.
Acknowledgements This study was sponsored by Pfizer Inc. Medical writing support was provided by Donna McGuire of Engage Scientific and was funded by Pfizer Inc
Disclosure of Interest P. Emery Grant/research support: AbbVie, BMS, MSD, Novartis, Pfizer, Roche, and UCB., Consultant for: AbbVie, BMS, MSD, Novartis, Pfizer, Roche, and UCB., R. Pedersen Shareholder of: Pfizer., Employee of: Pfizer., J. Bukowski Shareholder of: Pfizer., Employee of: Pfizer., L. Marshall Shareholder of: Pfizer., Employee of: Pfizer.