POS0682 LONG-TERM EFFICACY OF BARICITINIB IN PATIENTS WITH RHEUMATOID ARTHRITIS WITH INADEQUATE RESPONSE TO bDMARDs: RESULTS FROM RA-BEYOND FOLLOWING 6.9 YEARS OF TREATMENT

Abstract

BackgroundBaricitinib (BARI), an oral selective Janus kinase 1/2 inhibitor, is approved for treatment of adults with moderately-to-severely active rheumatoid arthritis (RA). BARI demonstrated efficacy in patients (pts) with RA who have inadequate response to biologic disease-modifying antirheumatic drugs (bDMARD-IR) in a 24-week (wk) phase 3 study, RA-BEACON.1 BARI efficacy was evaluated up to 3 years (yrs) of treatment in a long-term extension (LTE) study, RA-BEYOND.2ObjectivesDisclose long-term efficacy of BARI 4 mg and 2 mg in bDMARD-IR pts in the completed study RA-BEYOND.MethodsIn RA-BEACON, pts were randomized 1:1:1 to BARI 4 mg, 2 mg, or PBO; pts with no response could be rescued after wk 16. Completers to wk 24 could enter with BARI 4 or 2mg RA-BEYOND for up to 360 wks (6.9 yrs). LTE data were analysed by treatment assigned at baseline in RA-BEACON as observed up to time of stepdown (if applicable), study discontinuation, or study completion, whichever occurred earlier. Efficacy response rates (RR) were assessed as proportions of pts with observed data up to wk 360 for low-disease activity (LDA) (SDAI ≤ 11, DAS28-hsCRP ≤ 3.2, CDAI ≤ 10), remission (REM) (SDAI ≤ 3.3, DAS28-hsCRP < 2.6, CDAI ≤ 2.8, Boolean), and physical functioning (HAQ-DI ≤ 0.5). No formal statistical comparisons were conducted.Results156, 152, and 140 pts entered the LTE (4 mg, 2 mg, and PBO, respectively). Pts in BARI 4 and 2 mg arms had higher LDA and REM RR vs PBO at LTE entry (wk 24) (Table 1). PBO-treated pts achieved comparable RR to pts in the BARI 4 mg arm by wk 48 (24 wks after switch to BARI 4 mg) and up to wk 360. Of pts enrolled to RA-BEYOND, approx. 50% in BARI 4 mg, 65% in 2 mg and 61% in PBO remained active at wk 156; 17%, 26% and 26% at wk 360, respectively. SDAI LDA RR were 47%/70% and 61%/74% for pts treated with BARI 4 mg and 2 mg, at wk 156 (yr 3)/ 360 (yr 6.9), respectively; SDAI REM RR were 15%/26% and 26%/26% for BARI 4 mg and 2 mg, at wk 156/360, respectively (Table 1). SDAI and CDAI had comparable RR. DAS-28CRP LDA RR were similar to SDAI and CDAI, while REM RR were about twice those of SDAI and CDAI. HAQ-DI ≤ 0.5 RR was 15%/26% (BARI 4 mg), 21%/15% (BARI 2mg), and 9%/3% (PBO) at 3/6.9 yrs.Table 1.Efficacy outcomes in RA-BEYONDTimeaN/n (%)LDAREMSDAICDAIDAS-28 CRPSDAICDAIDAS-28 CRPBooleanHAQ-DI ≤0.5Wk 24PBOb135/31 (23.0)138/32 (23.2)135/31 (23.0)135/6 (4.4)138/8 (5.8)135/14 (10.4)135/3139/6 (4.3)(2.2)BARI 2 mg148/42 (28.4)152/43 (28.3)148/38 (25.7)148/10 (6.8)152/10 (6.6)148/22 (14.9)148/9152/17 (11.2)(6.1)BARI 4 mg150/57 (38.0)156/60 (38.5)150/60 (40.0)150/14 (9.3)156/17 (10.9)150/37 (24.7)150/11 (7.3)156/17 (10.9)Wk 48PBO128/59 (46.1)129/58 (45.0)128/58 (45.3)128/14 (10.9)129/15 (11.6)128/31 (24.2)128/5130/6 (4.6)(3.9)BARI 2 mg139/54 (38.8)140/56 (40.0)139/53 (38.1)139/13 (9.4)140/14 (10.0)139/30 (21.6)139/11 (7.9)140/16 (11.4)BARI 4 mg147/70 (47.6)149/71 (47.7)147/68 (46.3)147/22 (15.0)149/19 (12.8)147/49 (33.3)147/14 (9.5)149/19 (12.8)Wk 156PBO84/47 (56.0)85/47 (55.3)84/45 (53.6)84/15 (17.9)85/14 (16.5)84/33 (39.3)84/985/8 (9.4)(10.7)BARI 2 mg98/60 (61.2)99/60 (60.6)98/58 (59.2)98/25 (25.5)99/27 (27.3)98/43 (43.9)98/13 (13.3)99/21 (21.2)BARI 4 mg76/36 (47.4)78/35 (44.9)76/37 (48.7)76/11 (14.5)78/13 (16.7)76/25 (32.9)76/978/12 (15.4)(11.8)Wk 360PBO33/26 (78.8)35/25 (71.4)34/27 (79.4)33/8 (24.2)35/9 (25.7)34/17 (50.0)34/636/1 (2.8)(17.6)BARI 2 mg38/28 (73.7)38/28 (73.7)38/27 (71.1)38/10 (26.3)38/8 (21.1)38/20 (52.6)38/539/6 (15.4)(13.2)BARI 4 mg27/19 (70.4)27/20 (74.1)27/20 (74.1)27/7 (25.9)27/7 (25.9)27/15 (55.6)27/427/7 (25.9)(14.8)N: Number of pts with observed data; n: Number of pts with response. aNumber of wks from randomisation. bTreatment groups as assigned at randomisation.ConclusionIn observed data, BARI maintained efficacy and normative physical function bDMARD-IR population up to 6.9 yrs (360 wks).References[1]Genovese MC et al. N Engl J Med. 2016; 374:1243-52[2]Wells AF et al. Rheumatol Ther. 2021; 8:987–1001Disclosure of InterestsRoberto Caporali Speakers bureau: Abbvie, Amgen, BMS, Celltrion, Eli Lilly and Company, Galapagos, Pfizer, Fresenius-Kabi, MSD, UCB, Roche,Janssen, Novartis, Sandoz, Consultant of: Abbvie, Amgen, BMS, Celltrion, Eli Lilly and Company, Galapagos, Pfizer, MSD, UCB, Janssen, Novartis, Sandoz, Daniel Aletaha Speakers bureau: Abbvie, Amgen, Eli Lilly and Company, Janssen, Merck, Novartis, Pfizer, Roche, Sandoz, Grant/research support from: Abbvie, Amgen, Eli Lilly and Company, Novartis, Roche, SoBi, Sanofi, Raimón Sanmartí Speakers bureau: Eli Lilly and Company, Grant/research support from: Eli Lilly and Company, Tsutomu Takeuchi Speakers bureau: AbbVie Japan GK, Ayumi Pharmaceutical Co., Bristol Myers Squibb Co., Ltd., Chugai Pharmaceutical Co, Ltd. Daiichi Sankyo Co., Ltd. Eisai Co., Ltd. Eli Lilly Japan K.K.; Gilead Sciences, Inc. Janssen Pharmaceutical K.K.; Mitsubishi-Tanabe Pharma Co.; Novartis Pharma Co.; Pfizer Japan Inc.; Sanofi K.K.; UCB Japan Co., Ltd., Consultant of: AbbVie Japan GK, Astellas Pharma, Inc.; Chugai Pharmaceutical Co, Ltd.; Eli Lilly Japan K.K.; Eisai Co., Ltd.; Gilead Sciences, Inc.; Janssen Pharmaceutical K.K.; Mitsubishi-Tanabe Pharma Corp., Pfizer Japan Inc., Grant/research support from: AbbVie Japan GK, Asahikasei Pharma Corp., Chugai Pharmaceutical Co, Ltd., DNA Chip Research Inc.; Eisai Co., Ltd., Eli Lilly Japan K.K.; Mitsubishi-Tanabe Pharma Corp., UCB Japan Co., Ltd., Daojun Mo Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Ewa Haladyj Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Liliana Zaremba-Pechmann: None declared, Peter C. Taylor Consultant of: AbbVie, Biogen, Eli Lilly and Company, Fresenius, Galapagos, Gilead Sciences, GlaxoSmithKline, Janssen, Nordic Pharma, Pfizer Inc, Roche, and Sanofi, Grant/research support from: Celgene and Galapagos