THU0095 IMPACT OF BASELINE EROSION SCORE ON RESPONSE TO TREATMENT AND FUTURE RADIOLOGICAL DAMAGE IN AVERT-2, A RANDOMISED PHASE IIIB STUDY OF ABATACEPT IN MTX-NAÏVE, ANTI-CITRULLINATED PROTEIN ANTIBODY–POSITIVE (ACPA+) PATIENTS WITH EARLY RA
Authors: C. Pachai, S. Connolly, J. Landis, Y. Tanaka, V. Bykerk, T. Huizinga, G. Citera, C. Bingham, R. Wong, K. H. G. Huang, S. Du, W. Hayes, C. Wu, R. Fleischmann, P. Emery
Journal: Annals of the Rheumatic Diseases (2020)

Background: Bone erosions are associated with poor prognosis in patients (pts) with RA. They can be associated with subclinical inflammation and independently predict future radiological damage. 1 The Phase IIIb A ssessing V ery E arly R A T reatment (AVERT)-2 ( NCT02504268 ) trial evaluated abatacept (ABA)+MTX in MTX-naïve, ACPA+ pts with early RA. 2 Objectives: To explore the impact of baseline (BL) X-ray erosion scores (ES) on clinical response and future radiological damage over 1 yr in different groups of pts from AVERT-2. Methods: BL and Wk 52 X-ray data were evaluated using Sharp/van der Heijde score. SDAI remission rates (RRs; ≤3.3), unadjusted mean changes from BL (CfB) and duration of/time to sustained remission over 52 wks were evaluated. Radiographic progression was assessed at Wk 52 using CfB in ES. A range of BL ES cut-offs were evaluated to highlight key findings through comparison of pts with low and high ES. Results: Of 994 pts in the study, 964 (97%) had BL (median 2.0, interquartile range [IQR] 0.5–5.1) and 792 (80%) had BL and Wk 52 (median 2.5, IQR 1.0–6.5) ES. Results in Table 1 are based on ES cut-offs of 2 and 5, resulting in 53% and 75%, respectively, of pts in low ES groups. In pts who received ABA+MTX, those with low ES had higher SDAI RRs over 52 wks vs pts with high ES. The relationship was more pronounced for higher cut-offs. This was not observed with ABA placebo+MTX (MTX). Greater reduction of mean CfB in SDAI was achieved in pts with high vs low ES who received ABA+MTX. This was not observed with MTX. Pts who received ABA+MTX had longer duration and shorter time to sustained SDAI remission vs MTX. With ABA+MTX, pts with low ES had longer duration and shorter time to sustained SDAI remission vs high ES. This was not observed with MTX. Mean CfB in ES at Wk 52 was lower in the ABA+MTX arm vs the MTX arm. ABA seemed to equally protect pts with low and high ES; with MTX, pts with high ES had higher mean CfB in ES at Wk 52 than pts with low ES. Table 1. Key Findings Based on Low and High ES Cut-offs ABA+MTX ABA PBO +MTX ABA+MTX ABA PBO +MTX ES cut-off ≤2 &gt;2 ≤2 &gt;2 ≤5 &gt;5 ≤5 &gt;5 n (%) 377 (56) 294 (44) 131 (45) 162 (55) 516 (77) 155 (23) 207 (71) 86 (29) BL SDAI 37.4 (13.4) 40.6 (13.9) 37.7 (12.6) 40.6 (14.5) 37.5 (13.4) 42.9 (13.9) 38.6 (12.7) 41 (15.9) Wk 52 SDAI RR (≤3.3), % 35 29 20 16 34 26 17 19 CfB in SDAI –29.8 (14.3) –31.5 (13.7) –26.3 (13.6) –25.9 (15.3) –29.7 (14.0) –33.5 (13.9) –26.6 (13.4) –24.9 (16.7) CfB in ES 0.3 (1.1) 0.4 (2.0) 0.9 (2.0) 1.3 (3.0) 0.3 (1.2) 0.4 (2.4) 0.9 (2.0) 1.5 (3.6) Time to SDAI sREM, wks 18.7 (10.7) 22.0 (10.5) 24.7 (11.5) 22.5 (9.8) 19.6 (10.7) 22.0 (10.8) 23.1 (10.7) 24.2 (10.2) Duration of SDAI sREM, wks 24.1 (13.0) 22.0 (11.5) 18.7 (10.1) 20.5 (11.3) 23.5 (12.8) 21.9 (10.5) 19.8 (11.0) 19.6 (10.4) Data are mean (SD) unless otherwise stated sREM=sustained remission Conclusion: This erosion-based stratification of the AVERT-2 early seropositive RA population emphasizes the importance of treating pts prior to the accumulation of erosive disease. Abatacept+MTX led to higher SDAI RRs in pts with low vs high ES and provided further protection vs MTX alone against future radiological damage in pts with high ES. Additional statistical modelling and adjustment for confounding factors at BL is warranted. References: [1]van Nies JAB, et al. Ann Rheum Dis 2015; 74 :883–9. [2]Emery P, et al. ACR/ARHP 2018; Chicago, USA:abstract 563. Acknowledgments: Fiona Boswell (editorial assistance, Caudex; funding: Bristol-Myers Squibb) Disclosure of Interests: Chahin Pachai Employee of: Bristol-Myers Squibb, Sean Connolly Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Jessica Landis Employee of: Bristol-Myers Squibb, Yoshiya Tanaka Grant/research support from: Asahi-kasei, Astellas, Mitsubishi-Tanabe, Chugai, Takeda, Sanofi, Bristol-Myers, UCB, Daiichi-Sankyo, Eisai, Pfizer, and Ono, Consultant of: Abbvie, Astellas, Bristol-Myers Squibb, Eli Lilly, Pfizer, Speakers bureau: Daiichi-Sankyo, Astellas, Chugai, Eli Lilly, Pfizer, AbbVie, YL Biologics, Bristol-Myers, Takeda, Mitsubishi-Tanabe, Novartis, Eisai, Janssen, Sanofi, UCB, and Teijin, Vivian Bykerk: None declared, Thomas Huizinga Grant/research support from: Ablynx, Bristol-Myers Squibb, Roche, Sanofi, Consultant of: Ablynx, Bristol-Myers Squibb, Roche, Sanofi, Gustavo Citera Grant/research support from: AbbVie, Amgen, Eli Lilly, Gema, Genzyme, Novartis and Pfizer Inc, Consultant of: AbbVie, Amgen, Eli Lilly, Gema, Genzyme, Novartis and Pfizer Inc, Clifton Bingham Grant/research support from: Bristol-Myers Squibb, Consultant of: Bristol-Myers Squibb, Robert Wong Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Kuan-Hsiang Gary Huang Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Shuyan Du Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Wendy Hayes Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Chun Wu Employee of: Bristol-Myers Squibb, Roy Fleischmann Grant/research support from: AbbVie, Akros, Amgen, AstraZeneca, Bristol-Myers Squibb, Boehringer, IngelhCentrexion, Eli Lilly, EMD Serono, Genentech, Gilead, Janssen, Merck, Nektar, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc., Roche, Samsung, Sandoz, Sanofi Genzyme, Selecta, Taiho, UCB, Consultant of: AbbVie, ACEA, Amgen, Bristol-Myers Squibb, Eli Lilly, Gilead, GlaxoSmithKline, Novartis, Pfizer, Sanofi Genzyme, UCB, Paul Emery Grant/research support from: AbbVie, Bristol-Myers Squibb, Merck Sharp &amp; Dohme, Pfizer, Roche (all paid to employer), Consultant of: AbbVie (consultant, clinical trials, advisor), Bristol-Myers Squibb (consultant, clinical trials, advisor), Lilly (clinical trials, advisor), Merck Sharp &amp; Dohme (consultant, clinical trials, advisor), Novartis (consultant, clinical trials, advisor), Pfizer (consultant, clinical trials, advisor), Roche (consultant, clinical trials, advisor), Samsung (clinical trials, advisor), Sandoz (clinical trials, advisor), UCB (consultant, clinical trials, advisor)