FRI0090 MAINTENANCE OF CLINICAL RESPONSE WITH ABATACEPT IN COMBINATION WITH MTX IN INDIVIDUAL PATIENTS WITH EARLY RA WHO ARE MTX-NAÏVE AND ANTI-CITRULLINATED PROTEIN ANTIBODY (ACPA)+: RESULTS FROM THE INDUCTION PERIOD OF AVERT-2, A RANDOMISED PHASE IIIB STUDY
Authors: P. Emery, Y. Tanaka, V. Bykerk, C. Bingham, T. Huizinga, G. Citera, K. H. G. Huang, S. Connolly, Y. Elbez, R. Wong, K. Lozenski, R. Fleischmann
Journal: Annals of the Rheumatic Diseases (2020)

Background: In the 56-wk induction period (IP) of the Phase IIIb A ssessing V ery E arly R A T reatment (AVERT)-2 trial ( NCT02504268 ), more patients (pts) achieved SDAI remission (≤3.3) with abatacept (ABA) + MTX vs ABA placebo (PBO) + MTX at IP Wk 52. 1 It is unknown whether each individual pt within a treatment (Tx) group achieves and sustains the same efficacy endpoints at all time points during the IP. Objectives: To investigate whether ABA effectiveness is sustained by individual pts who achieved SDAI remission (≤3.3), SDAI low disease activity (LDA; &gt;3.3–11), DAS28 (CRP) &lt;2.6, ACR50/70 response or Boolean remission at IP Wk 24 (AVERT-2 primary endpoint) and both Wks 40 and 52 (Wks 40/52). Methods: Pts were randomised 3:2 to blinded SC ABA (125 mg/wk) + MTX or ABA PBO + MTX induction Tx for 56 wks. Key inclusion criteria: age ≥18 yrs; RA diagnosis (ACR/EULAR 2010 criteria); RA duration ≤6 mos; SDAI &gt;11; ACPA+; CRP &gt;3 mg/L or ESR ≥28 mm/h; TJC ≥3 and SJC ≥3; DMARD naïve. Response rates were investigated by Tx arm in the cohort 1 analysis population (all randomised pts treated in the IP [intent-to-treat analysis]). Results: Of randomised cohort 1, 752 pts were treated during the IP: 451 with ABA + MTX and 301 with ABA PBO + MTX. Baseline characteristics were similar across Tx arms. 1 Stringent SDAI remission endpoint at IP Wk 24 was achieved by 22% of ABA + MTX-treated pts; of these, 56% sustained SDAI remission at IP Wks 40/52 (Table). A similar proportion of ABA + MTX-treated pts achieved (17%) and sustained (58%) Boolean remission at IP Wks 24 and 40/52. At IP Wk 24, 42% of ABA + MTX-treated pts achieved DAS28 (CRP) &lt;2.6 and 74% sustained DAS28 (CRP) &lt;2.6 to IP Wks 40/52; a high proportion of patients sustained ACR50/70 responses at IP Wks 40/52 (83% and 79%, respectively). A lower proportion of pts sustained SDAI LDA to IP Wks 40/52 vs other endpoints (Table). Most efficacy endpoints were achieved by fewer pts who received ABA PBO + MTX than ABA + MTX (Table); among responders in this Tx group, fewer sustained remission at Wks 40/52, which correlates with a higher proportion of pts sustaining SDAI LDA at Wks 40/52 with ABA PBO + MTX than ABA + MTX. Conclusion: The majority of individual pts with RA who achieved clinically stringent endpoints such as SDAI remission, DAS28 (CRP) &lt;2.6 or Boolean remission, as well as clinically meaningful endpoints such as ACR50/70 at IP Wk 24 with weekly SC abatacept, sustained their responses to Wks 40/52. The high proportion of patients achieving early stringent remission and response to SC abatacept by individual pts may be indicative of sustained efficacy over time. References: [1]Emery P, et al. ACR 2018; San Diego, USA: Poster 563. Table . Proportion of Pts With Response at IP Wk 24 Who Also Achieved Remission at Wks 40/52 Endpoint Responders at IP Wk 24, n (%) Responders at IP Wk 24 and Wks 40/52, n/N (%) ABA + MTX (n=451) ABA PBO + MTX (n=301) ABA + MTX* ABA PBO + MTX* SDAI remission (≤3.3) 100 (22) 40 (13) 56/100 (56) 17/40 (43) SDAI low disease activity (&gt;3.3–11) 167 (37) 82 (27) 46/167 (28) 32/82 (39) DAS28 (CRP) &lt;2.6 188 (42) 78 (26) 139/188 (74) 43/78 (55) ACR50 response † 260 (58) 125 (42) 215/260 (83) 92/125 (74) ACR70 response † 156 (35) 66 (22) 123/156 (79) 42/66 (64) Boolean remission 76 (17) 29 (10) 44/76 (58) 8/29 (28) *% based on number of pts within each Tx group who achieved response at IP Wk 24 (denominator); † Response at IP Wks 24 and 52 Acknowledgments: Lola Parfitt (medical writing, Caudex; funding: Bristol-Myers Squibb) Disclosure of Interests: 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), 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, Clifton Bingham Grant/research support from: Bristol-Myers Squibb, Consultant of: Bristol-Myers Squibb, 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, Kuan-Hsiang Gary Huang Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Sean Connolly Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Yedid Elbez Consultant of: Bristol-Myers Squibb, Robert Wong Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Karissa Lozenski 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