ACPA POSITIVITY DETERMINES REMISSION IN PATIENTS WITH RA TREATED WITH IV AND SC ABATACEPT: A POST HOC ANALYSIS OF THE REAL-WORLD OBSERVATIONAL ACTION AND ASCORE STUDIES

BackgroundThe goal of treatment for RA is achieving low disease activity and/or remission1,2; however, disease course and management can be complicated by additional factors that may be influenced by serostatus. Anti-citrullinated protein antibodies (ACPAs) and RF contribute to a more severe RA disease pattern3 and may be useful in predicting response to treatment.4 ACTION (AbataCepT In rOutiNe clinical practice; NCT02109666) and ASCORE (Abatacept SubCutaneOus in Routine Clinical PracticE; NCT02090556) were 2-year, international, observational, prospective, multicenter studies of IV and SC abatacept, respectively, for the treatment of RA in routine clinical practice.4,5 Previous analyses have shown that ACPA/RF double-positive serostatus was associated with better treatment outcomes compared with ACPA/RF double-negative serostatus.4–6ObjectivesTo assess the independent effect of ACPA or RF single seropositivity among patients with RA on achieving remission after treatment with abatacept for 2 years, and to compare outcomes among patients with single versus double serostatus.MethodsThis post hoc analysis included patients from ACTION and ASCORE who initiated IV (body weight–adjusted dosing) or SC abatacept (125 mg once weekly), respectively. Patients were stratified by baseline ACPA/RF status: ACPA+/RF− (ACPA+ only), ACPA/RF double positive (+/+), ACPA−/RF+ (RF+ only), and ACPA/RF double negative (−/−). DAS28 (CRP) and CDAI remission rates (defined as < 2.6 and 0–2.8, respectively) at 2 years for patients who were ACPA+ or RF+ only at baseline were assessed and compared with those who were +/+ and −/−. Patients with missing baseline ACPA/RF status were excluded. Last observation carried forward efficacy analyses were used to impute missing values.ResultsThis analysis included 1679 patients from ACTION (ACPA+ only, n = 98; +/+, n = 1028; RF+ only, n = 161; and −/−, n = 392) and 1748 patients from ASCORE (ACPA+ only, n = 184; +/+, n = 1079; RF+ only, n = 142; and −/−, n = 343). Across studies and serogroups, baseline demographics and disease characteristics were similar (data not shown). In both ACTION and ASCORE, a higher proportion of patients who were only ACPA+ achieved DAS28 (CRP) and CDAI remission at 2 years compared with patients who were only RF+ (Figure 1). Additionally, a similar proportion of patients who were only ACPA+ achieved DAS28 (CRP) and CDAI remission at 2 years compared with patients who were +/+. In contrast, a lower proportion of patients who were only RF+ achieved DAS28 (CRP) and CDAI remission at 2 years compared with patients who were +/+.ConclusionIn this post hoc analysis of real-world data from ACTION and ASCORE, ACPA positivity was associated with an increased likelihood of achieving DAS28 (CRP) and CDAI remission at 2 years. Patients who were ACPA+ only were as likely to achieve remission as +/+ patients, suggesting that RF serostatus had less influence than ACPA serostatus on remission status at 2 years. In line with this, patients who were RF+ only were less likely to achieve remission at 2 years. This is the first large, real-world study to show that ACPA positivity plays a more important role than RF positivity in achieving remission whilst on abatacept. These results highlight the importance of assessing baseline ACPA status when considering treatment options for patients with RA.References[1]Smolen JS, et al. Ann Rheum Dis 2020;79:685–99.[2]Fraenkel L, et al. Arthritis Care Res (Hoboken) 2021;73:924–39.[3]Katchamart, W, et al. Rheumatol Int 2015;35:1693–9.[4]Alten R, et al. Ann Rheum Dis 2021;80(suppl 1):OP0180.[5]Alten R, et al. Clin Rheumatol 2019;38:1413–24.[6]Alten R, et al. RMD Open 2017;3:e000345.AcknowledgementsThis study was sponsored by Bristol Myers Squibb. Medical writing and editorial assistance was provided by Rachel Rankin, PhD, of Caudex, and was funded by Bristol Myers Squibb. Study management provided by Syneos (CRO).Disclosure of InterestsRieke Alten Speakers bureau: AbbVie, Bristol Myers Squibb, Celltrion, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, Roche, Paid instructor for: AbbVie, Bristol Myers Squibb, Celltrion, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, Roche, Consultant of: AbbVie, Bristol Myers Squibb, Celltrion, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, Roche, Grant/research support from: AbbVie, Bristol Myers Squibb, Celltrion, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, Roche, Christiane Rauch Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Melanie Chartier Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, M.T. Nurmohamed Speakers bureau: AbbVie, Bristol Myers Squibb, Eli Lilly, Janssen, Pfizer, Consultant of: AbbVie, Bristol Myers Squibb, Eli Lilly, Janssen, Pfizer, Grant/research support from: AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Galapagos, Janssen, MSD, Pfizer, Sean Connolly Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Maya H Buch Speakers bureau: AbbVie, Consultant of: AbbVie, Galapagos, Gilead, Pfizer, Grant/research support from: Gilead, Pfizer, UCB, Peter Peichl Speakers bureau: Janssen, GlaxoSmithKline, Xavier Mariette Consultant of: Bristol Myers Squibb, Galapagos, GlaxoSmithKline, Janssen, Novartis, Pfizer, Sanofi, UCB, Yusuf Patel: None declared, Sara Marsal Speakers bureau: Bristol Myers Squibb, Lilly, MSD, Novartis - Sandoz, Pfizer, Roche, Consultant of: AbbVie, Galapagos, Pfizer, Sanofi; IMIDomics (executive role), Grant/research support from: AbbVie, Bristol Myers Squibb, Galapagos, Janssen, Lilly, MSD, Novartis - Sandoz, Pfizer, Roche, Sanofi, UCB, Roberto Caporali Speakers bureau: AbbVie, Amgen, Bristol Myers Squibb, Celltrion, Fresenius-Kabi, Galapagos, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, Sandoz, UCB, Consultant of: AbbVie, Amgen, Bristol Myers Squibb, Celltrion, Galapagos, Janssen, Lilly, MSD, Novartis, Pfizer, Sandoz, UCB, Hedley Griffiths Consultant of: Amgen, Raimón Sanmartí Speakers bureau: AbbVie, Bristol Myers Squibb, Lilly, MSD, Pfizer, Roche, Sanofi, Grant/research support from: AbbVie, Bristol Myers Squibb, MSD, Pfizer, Roche, Bettina Bannert: None declared, Yedid Elbez Consultant of: Bristol Myers Squibb, Employee of: Signifience, Karissa Lozenski Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb