Date: Sunday, November 8, 2015
Session Type: ACR Poster Session A
Session Time: 9:00AM-11:00AM
Background/Purpose: Assessing Very Early Rheumatoid arthritis Treatment (AVERT) was a Phase IIIb, randomized, active-controlled study to evaluate the efficacy and safety of abatacept (ABA) treatment in three phased periods: during treatment, following withdrawal of all therapies and during re-exposure. Here, we present data from the withdrawal and re-exposure periods.
Methods: MTX-naïve, anti-cyclic citrullinated peptide 2-positive patients (pts) with early RA (active synovitis in ≥2 joints for ≥8 wks, DAS28 [CRP] ≥3.2 and onset of symptoms within ≤2 yrs) were initially randomized to 12 months of weekly SC ABA 125 mg + MTX, ABA 125 mg monotherapy or MTX alone (treatment period). Pts with DAS28 (CRP) <3.2 at Month 12 then entered a 12-month withdrawal period with no treatment. All pts with protocol-defined flare after Month 15 could receive open-label ABA + MTX (re-exposure period) for 6 months.
Results: Most pts could not remain treatment-free after complete treatment withdrawal, due to worsening disease activity (172/225; 76.4%) during the 12-month withdrawal period. Of those who entered the withdrawal period, rates of pts maintaining DAS28 (CRP) <2.6 free of all drugs at 24 months were 14.0, 12.3 and 11.3% for ABA + MTX, ABA mono and MTX alone, respectively. Rates of pts ever achieving a major clinical response (MCR) at 24 months were 40.3, 25.9 and 15.5% for ABA + MTX, ABA mono and MTX alone, respectively. A total of 146 pts entered the re-exposure period and 140 completed. Their baseline demographics and disease characteristics were similar to those of pts at study entry (mean RA duration ~0.5 yrs). The mean (SD) DAS28 at re-exposure period entry was 5.47 (1.27) and, at the end of the re-exposure period, was 2.43 (0.95). A total of 62% (78/126) of evaluable pts were in DAS28 (CRP) remission on re-exposure period Day 169. The mean (SD) HAQ at re-exposure period entry was 1.45 (0.64) and, at the end of the re-exposure period, was 0.63 (0.57). Over 12 months of the withdrawal period, the numbers (%) of serious AEs were 2 (2.4), 0 (0) and 5 (6.7), respectively, and only 1 serious infection was reported in the MTX alone arm (pyelonephritis; 337.4 pt-yrs). In the re-exposure period, no pts discontinued due to AEs and no serious infections were reported (292.2 pt-yrs). The overall rates of infections were 8.9 and 16 (incidence rate/100 pt-yrs) in the withdrawal and re-exposure periods, respectively (overall rates were 110.7 and 72.8 in the first and second 6 months of the initial treatment period). Multivariate analysis to identify predictors of time to flare and achieving DAS28 (CRP) <2.6 in the re-exposure period will be presented.
Conclusion: Re-treatment with abatacept + MTX can effectively recapture prior remission following flare after complete withdrawal of therapy. The likelihood of ever achieving a MCR was more likely in pts in the abatacept + MTX arm (> abatacept > MTX). There were far fewer infection events in the combined withdrawal period and re-exposure period than in the initial treatment period and only 1 serious infection was reported in the combined withdrawal period and treatment period suggesting re-treatment is well tolerated.
To cite this abstract in AMA style:Emery P, Burmester G, Bykerk V, Combe B, Furst DE, Maldonado M, Huizinga TWJ. Abatacept Plus Methotrexate Can Effectively and Safely Regain the Target of Remission Following Re-Treatment for Flares after Drug-Free Withdrawal in Patients with Early Rheumatoid Arthritis [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). http://acrabstracts.org/abstract/abatacept-plus-methotrexate-can-effectively-and-safely-regain-the-target-of-remission-following-re-treatment-for-flares-after-drug-free-withdrawal-in-patients-with-early-rheumatoid-arthritis/. Accessed January 20, 2018.
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