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Abstract
Background AVERT was a Phase IIIb, randomized, active-controlled study to evaluate the efficacy and safety of abatacept (ABA) treatment in three phases: treatment period (TP), withdrawal period (WP) and re-exposure period (RP). The TP and first 6 months (M) of the WP have previously been reported.1
Objectives To describe efficacy and safety of re-treatment with ABA + MTX following RA disease flare after all treatment withdrawal.
Methods MTX-naïve, anti-cyclic citrullinated peptide-2-positive patients (pts) with early RA (active synovitis in ≥2 joints for ≥8 weeks, DAS28 [CRP] ≥3.2 and symptom onset within ≤2 years) were randomized to 12M of weekly SC ABA 125 mg + MTX, ABA 125 mg monotherapy (mono) or MTX alone. Pts with DAS28 (CRP) <3.2 at M12 entered a 12M WP with no treatment, including corticosteroids. All pts with protocol-defined flare after 15M could receive open-label weekly SC ABA 125 mg + MTX 10–20 mg (RP) for 6M. Baseline for the RP was the last assessment within 30 days before the first re-exposure dose. For pts who entered the RP, time to first flare after withdrawal (Kaplan–Meier [KM] curves) and predictors of shorter times to flare (Cox proportional hazard model), and DAS28 (CRP) remission during re-exposure (adjusted logistic regression), were modeled.
Results Most pts entered the WP (225/351); of 176 pts with DAS28 (CRP) <2.6 at 12M, only 12.3, 14.0 and 11.3% for ABA + MTX, ABA mono and MTX alone, respectively, maintained DAS28 (CRP) <2.6 free of all drugs at 24M. The KM curves for time to first flare during WP for pts entering the RP are shown (Figure). Corticosteroid use at study entry was associated with shorter time to flare. In total, 146 pts from all three groups entered the RP; baseline characteristics were similar to those of pts at study entry (mean RA duration ∼0.5 yrs). Mean (SD) DAS28 (CRP) was 5.28 (1.37) at RP baseline and 2.41 (0.94) at the end of RP (mean change: –2.87 [0.13], n=120). In total, 76.6% (95/124) of evaluable pts had low disease activity (DAS28 [CRP] <3.2) on RP Day 169, with 62.9% (78/124) in remission (DAS28 [CRP] <2.6). Mean (SD) HAQ at RP entry was 1.40 (0.63), and 0.64 (0.57) at the end of the RP. Pt assessment of disease activity was significantly associated with DAS28 (CRP) remission during the RP. Over the 12M WP, the numbers (%) of serious AEs were 2 (2.4), 0 (0) and 5 (6.7), respectively; only one serious infection was reported (MTX alone; pyelonephritis; 337.4 pt-yrs). In the RP, no pts discontinued due to AEs and no serious infections were reported (292.2 pt-yrs). Overall rates of infections were 8.1 and 16.1 (incidence rate/100 pt-yrs) in the WP and RP. In the TP, incidence rates of infections were 116.6, 126.1 and 110.7/100 pt-yrs from 0–6M, and 64.6, 66.5 and 72.8/100 pt-yrs from 6–12M for ABA + MTX, ABA mono and MTX alone.
Conclusions Re-treatment with abatacept + MTX can effectively recapture prior remission following flare after complete withdrawal of therapy. The lower rate of infections in the RP versus initial TP suggests re-treatment is well tolerated.
Emery P, et al. Ann Rheum Dis 2015;74:19–26.
Disclosure of Interest P. Emery Grant/research support from: AbbVie, Merck, Pfizer, Roche, Consultant for: AbbVie, Bristol-Myers Squibb, Merck, Pfizer, Roche, Lilly, Novartis, Samsung Bioepis, G. Burmester Grant/research support from: Clinical trials for BMS, AbbVie, Pfizer, Medimmune, Novartis, Roche, UCB, Lilly, Consultant for: Bristol-Myers Squibb, AbbVie, Pfizer, MSD, MedImmune, Roche, UCB, Speakers bureau: Bristol-Myers Squibb, AbbVie, Pfizer, MSD, Roche, UCB, V. Bykerk Grant/research support from: Amgen, Pfizer, BMS, Janssen, UCB, Sanofi, Roche/Genentech, Consultant for: Amgen, AbbVie, Pfizer, Bristol-Myers Squibb, UCB, Roche, Regeneron, B. Combe Grant/research support from: Pfizer, Roche-Chugai, UCB, Speakers bureau: Bristol-Myers Squibb, Merck, Pfizer, Roche-Chugai, UCB, Janssen, Lilly, Novartis, D. E. Furst Grant/research support from: AbbVie, Actelion, Amgen, Bristol-Myers Squibb, Gilead, GSK, NIH, Novartis, Pfizer, Roche/Genentech, UCB, Consultant for: AbbVie, Actelion, Amgen, Bristol-Myers Squibb, Cytori, Janssen, Gilead, GSK, NIH, Novartis, Pfizer, Roche/Genentech, UCB, Speakers bureau: AbbVie, Actelion, UCB, M. A. Maldonado Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, T. W. Huizinga Grant/research support from: EU & Dutch Arthritis Foundation, Consultant for: Abbott Laboratories, Biotest AG, Bristol-Myers Squibb, Crescendo Bioscience, Novartis, Pfizer, Roche, sanofi-aventis, Schering-Plough, UCB, Eli Lilly, Speakers bureau: Abbott Laboratories, Biotest AG, Bristol-Myers Squibb, Novartis, Pfizer, Roche, sanofi-aventis, Schering-Plough