OP0026 Induction of Clinical Remission Followed by Drug-Free Withdrawal with Abatacept Combination and Monotherapy in Early RA: Results from the AVERT Study over 18 Months
Authors: P. Emery, G. Burmester, V. Bykerk, B. Combe, D.E. Furst, E. Barre, C.S. Karyekar, D. Wong, T.W. Huizinga
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> AVERT (Assessing Very Early Rheumatoid arthirits Treatment) is a Phase IIIb, randomized, active-controlled study to evaluate the efficacy and safety of subcutaneous (SC) abatacept (ABA) in pts with early RA. <h3>Objectives</h3> To assess ABA + MTX or ABA monotherapy in inducing clinical remission at 12 mths and then maintain it following rapid withdrawal of all RA treatment (biologics, DMARDs, steroids) in pts with early RA. <h3>Methods</h3> MTX-naïve, anti-CCP2+ pts with early RA (active synovitis in ≥2 joints for ≥8 wks, DAS28 (CRP) &gt;3.2 and onset of symptoms within ≤2 yrs) were included. Pts were randomized to 12 mths of weekly SC ABA 125 mg + MTX, ABA 125 mg monotherapy or MTX alone. Pts with DAS28 (CRP) &lt;3.2 at Mth 12 entered a 12-mth withdrawal period with no treatment. All pts with protocol-defined flare after Mth 15 could receive open-label ABA + MTX. The co-primary endpoints compared ABA + MTX and MTX alone in pts achieving DAS28 (CRP) &lt;2.6 at (1) 12 mths and (2) both 12 and 18 mths. ABA monotherapy was also assessed. <h3>Results</h3> 351 pts (n=119, 116 and 116 pts in the ABA + MTX, ABA and MTX arms, respectively) with early RA, highly active disease and poor prognosis (at baseline: mean RA duration of 0.56 yrs, mean DAS28 (CRP) of 5.4, mean HAQ of 1.4; 95.2% RF+ and anti-CCP2+) entered the study. At 12 mths, 60.9, 42.5 and 45.2% achieved DAS28 (CRP) &lt;2.6 (ABA + MTX, ABA and MTX, respectively). Odds ratio (OR; 95% CI) for ABA + MTX vs MTX: 2.01 (1.18, 3.43) with p=0.01 and for ABA vs MTX: 0.92 (0.55, 1.57). At most time points, efficacy on signs and symptoms in the ABA monotherapy arm fell between the ABA + MTX and MTX arms (Figure) based on DAS28 (CRP) as well as other measures. Following treatment withdrawal, most pts discontinued due to increase in disease activity (177/223; 79.4%). Rates of pts achieving DAS28 (CRP) &lt;2.6 at both 12 and 18 mths were 14.8, 12.4 and 7.8% for ABA + MTX, ABA and MTX, respectively; OR (95% CI) for ABA + MTX vs MTX: 2.51 (1.02, 6.18), p=0.045 and for ABA vs MTX: 2.04 (0.81, 5.14). In a <i>post hoc</i> analysis, pts who maintained DAS28 (CRP) &lt;2.6 at both Mth 12 and 18 tended to have numerically lower baseline mean symptom duration, DAS28 (CRP), HAQ score and DAS28 (CRP) &lt;2.6 over time during the treatment period compared with pts who achieved only DAS28 (CRP) &lt;2.6 at 12 mths. Over 12 mths of treatment, the number (%) of serious adverse events was 8 (6.7), 14 (12.1) and 9 (7.8) and the number (%) of serious infections was 1 (0.8), 4 (3.4) and 0 in the ABA + MTX, ABA and MTX arms, respectively. <h3>Conclusions</h3> In this study, in pts with highly active early RA with poor prognosis, abatacept + MTX resulted in significantly higher rates of remission and comparable safety vs MTX alone at 12 mths. At most time points, abatacept monotherapy was more effective than MTX alone. A small but significantly higher number of patients treated with abatacept + MTX were able to maintain drug-free remission compared to MTX. <h3>Disclosure of Interest</h3> P. Emery Grant/research support: AbbVie, BMS, Merck, Pfizer, Roche, Consultant for: AbbVie, BMS, Merck, Pfizer, Roche, Takeda, G. Burmester Grant/research support: BMS, AbbVie, Pfizer, Medimmune, Novartis, Roche, UCB, Lilly, Consultant for: BMS, AbbVie, Pfizer, MSD, Medimmune, Roche, UCB, Speakers bureau: BMS, AbbVie, Pfizer, MSD, Roche, UCB, V. Bykerk Grant/research support: Amgen, Pfizer, BMS, Janssen, UCB, Roche/Genentech, B. Combe Grant/research support: Pfizer, Roche-Chugai, Speakers bureau: BMS, Merck, Pfizer, Roche-Chugai, UCB, D. Furst Grant/research support: AbbVie, Actelion, Amgen, BMS, Gilead, GSK, NIH, Novartis, Pfizer, Roche/Genentech, UCB, Consultant for: AbbVie, Actelion, Amgen, BMS, Janssen, Gilead, GSK, NIH, Novartis, Pfizer, Roche/Genentech, UCB, Speakers bureau: AbbVie, Actelion, UCB, E. Barre Employee of: BMS, C. Karyekar Employee of: BMS, D. Wong Employee of: BMS, T. Huizinga Grant/research support: EU &amp; Dutch Arthritis Foundation, Consultant for: Abbott Laboratories, Biotest AG, Bristol-Myers Squibb, Crescendo Bioscience, Inc, Novartis Pharmaceuticals Corporation, Pfizer Inc, Roche, sanofi-aventis, Schering-Plough, UCB, Inc., Eli Lilly, Speakers bureau: Abbott Laboratories, Biotest AG, Bristol-Myers Squibb, Novartis Pharmaceuticals Corporation, Pfizer Inc, Roche, sanofi-aventis, Schering-Plough <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2132