Pos1537 bimekizumab efficacy and safety in biologic dmard-naïve patients with psoriatic arthritis was consistent with or without methotrexate: 52-week results from the phase 3 active‑reference study be optimal

Background Given the chronic nature of psoriatic arthritis (PsA), understanding long-term efficacy and safety of biologic monotherapy or therapy in combination with ongoing methotrexate (MTX) is of interest. Studies have shown reduced efficacy of tumour necrosis factor inhibitors without MTX than with MTX [1] . Bimekizumab (BKZ), a monoclonal IgG1 antibody that selectively inhibits IL-17F in addition to IL-17A, has shown efficacy and tolerability to 52 weeks (wks) in patients (pts) with PsA [2] . Objectives To report BKZ efficacy and safety to Wk 52 from the phase 3 study BE OPTIMAL in bDMARD-naïve pts with PsA, with or without ongoing concomitant MTX. Methods BE OPTIMAL ( NCT03895203 ) comprised a 16-wk double-blind placebo (PBO)-controlled period and a 36-wk active treatment-blind period. Pts were randomised 3:2:1 subcutaneous BKZ 160 mg every 4 wks (Q4W):PBO:reference arm (adalimumab [ADA] 40 mg Q2W). From Wk 16, PBO pts received BKZ 160 mg Q4W. Pts could not adjust their background medication during the 16-wk PBO-controlled period. Efficacy and safety were evaluated by concomitant MTX use at baseline (BL). Missing data were imputed using non-responder (discrete) or multiple (continuous) imputation. Results 761/852 (89.3%) pts completed Wk 52 (+ MTX: 454/497 [91.3%], – MTX: 307/355 [86.5%]). BL characteristics were generally similar +/– MTX: mean age 48.1 vs 49.4 years, BMI 29.1 vs 29.4 kg/m 2 , 5.7 vs 6.2 years since diagnosis, 47.3% vs 46.2% male, 49.5% vs 50.4% with psoriasis affecting ≥3% body surface area. To Wk 52, the proportion of BKZ-randomised pts who achieved American College of Rheumatology (ACR)50, complete skin clearance (Psoriasis Area and Severity Index [PASI]100) and minimal disease activity (MDA) were similar regardless of BL MTX use. Fewer pts receiving ADA – MTX achieved ACR50 or MDA at Wk 52 compared to ADA + MTX ( Figure 1 ). Other Wk 52 efficacy responses on BKZ were generally of a similar magnitude +/– MTX ( Table 1 ). To Wk 52, pts with ≥1 treatment-emergent adverse event +/– MTX: PBO/BKZ 124/158 (78.5%) vs 89/113 (78.8%), BKZ 214/252 (84.9%) vs 150/179 (83.8%), ADA 63/82 (76.8%) vs 50/58 (86.2%). Conclusion BKZ treatment demonstrated consistent sustained clinical efficacy across disease manifestations to Wk 52 in bDMARD-naïve pts with PsA, irrespective of concomitant MTX. BKZ was well tolerated in pts with PsA with or without MTX. References [1]Smolen JS. Rheumatol Ther 2020;7:1021–35; [ 2] Ritchlin C. Arthritis Rheumatol 2022;74(S9). Table 1. Wk 52 efficacy endpoints for pts +/– MTX Endpoint PBO/BKZ 160 mg Q4W N=281 BKZ 160 mg Q4W N=431 Reference Arm (ADA 40 mg Q2W)N=140 + MTX n=163 – MTX n=118 + MTX n=252 – MTX n=179 + MTX n=82 – MTX n=58 ACR20 [NRI], n (%) 113 (69.3) 78 (66.1) 184 (73.0) 123 (68.7) 65 (79.3) 37 (63.8) ACR70 [NRI], n (%) 60 (36.8) 41 (34.7) 96 (38.1) 73 (40.8) 36 (43.9) 17 (29.3) PASI75 a [NRI], n (%) 71 (85.5) 48 (84.2) 105 (83.3) 72 (79.1) 23 (62.2) 22 (71.0) PASI90 a [NRI], n (%) 67 (80.7) 39 (68.4) 89 (70.6) 66 (72.5) 20 (54.1) 21 (67.7) VLDA [NRI], n (%) 35 (21.5) 27 (22.9) 72 (28.6) 53 (29.6) 25 (30.5) 14 (24.1) ACR50+PASI100 a [NRI], n (%) 43 (51.8) 22 (38.6) 61 (48.4) 41 (45.1) 12 (32.4) 12 (38.7) HAQ-DI CfB [MI], mean (SE) −0.37 (0.04) −0.37 (0.05) −0.30 (0.03) −0.38 (0.04) −0.49 (0.06) −0.30 (0.08) Enthesitis resolution b [NRI], n (%) 24 (66.7) 20 (58.8) 53 (64.6) 34 (55.7) 11 (61.1) 10 (55.6) Dactylitis resolution c [NRI], n (%) 18 (81.8) 11 (100.0) 21 (75.0) 24 (85.7) 4 (80.0) 4 (66.7) Nail psoriasis resolution d [NRI], n (%) 68 (73.9) 43 (67.2) 100 (68.5) 60 (61.2) 24 (57.1) 21 (63.6) Randomised set. a In pts with BL psoriasis ≥3% BSA; + MTX: PBO/BKZ n=83; BKZ n=126; ADA n=37; – MTX: PBO/BKZ n=57; BKZ n=91; ADA n=31. b In pts with BL enthesitis (LEI >0); + MTX: PBO/BKZ n=36; BKZ n=82; ADA n=18; – MTX: PBO/BKZ n=34; BKZ n=61; ADA n=18. c In pts with BL dactylitis (LDI >0); + MTX: PBO/BKZ n=22; BKZ n=28; ADA n=5; – MTX: PBO/BKZ n=11; BKZ n=28; ADA n=6. d In pts with BL nail psoriasis (mNAPSI >0); + MTX: PBO/BKZ n=92; BKZ n=146; ADA n=42; – MTX: PBO/BKZ n=64; BKZ n=98; ADA n=33. Acknowledgements This study was funded by UCB Pharma. Medical writing support was provided by Costello Medical, funded by UCB Pharma. Prof. Richard B. Warren is supported by the NIHR Manchester Biomedical Centre. Disclosure of Interests Iain McInnes Consultant of: Consulting fees and honoraria from AbbVie, AstraZeneca, BMS, Boehringer Ingelheim, Cabaletta, Causeway Therapeutics, Celgene, Evelo, Janssen, Lilly, MoonLake, Novartis and UCB Pharma, Grant/research support from: BMS, Boehringer Ingelheim, Celgene, Janssen, Novartis and UCB Pharma, Philip J Mease Speakers bureau: AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer and UCB Pharma, Consultant of: AbbVie, Acelyrin, Aclaris, Amgen, BMS, Boehringer Ingelheim, Eli Lilly, Galapagos, Gilead, GSK, Janssen, MoonLake Pharma, Novartis, Pfizer, Sun Pharma and UCB Pharma, Grant/research support from: AbbVie, Amgen, BMS, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, Sun Pharma and UCB Pharma, Yoshiya Tanaka Speakers bureau: Speaking fees and/or honoraria from AbbVie, AstraZeneca, BMS, Boehringer Ingelheim, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, GSK, Mitsubishi Tanabe and Pfizer, Grant/research support from: AbbVie, Asahi-Kasei, Boehringer Ingelheim, Chugai, Daiichi Sankyo, Eisai and Takeda, Frank Behrens Speakers bureau: Consultant and/or speaker and/or investigator for AbbVie, Affibody, Amgen, Boehringer Ingelheim, Celgene, Chugai, Eli Lilly, Genzyme, GSK, Janssen, MoonLake, MSD, Novartis, Pfizer, Roche, Sandoz and Sanofi, Consultant of: Consultant and/or speaker and/or investigator for AbbVie, Affibody, Amgen, Boehringer Ingelheim, Celgene, Chugai, Eli Lilly, Genzyme, GSK, Janssen, MoonLake, MSD, Novartis, Pfizer, Roche, Sandoz and Sanofi, Grant/research support from: Consultant and/or speaker and/or investigator for AbbVie, Affibody, Amgen, Boehringer Ingelheim, Celgene, Chugai, Eli Lilly, Genzyme, GSK, Janssen, MoonLake, MSD, Novartis, Pfizer, Roche, Sandoz and Sanofi, Laure Gossec Consultant of: AbbVie, Amgen, BMS, Celltrion, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Pfizer, Sandoz and UCB Pharma, Grant/research support from: Sandoz and UCB Pharma, M Elaine Husni Consultant of: Advisory board member and consultant for AbbVie, Amgen, BMS, Eli Lilly, Janssen, Novartis, Pfizer and UCB Pharma, Lars Erik Kristensen Speakers bureau: Speaking fees from/consultant for AbbVie, Amgen, Biogen, BMS, Eli Lilly, Gilead, Janssen, MSD, Novartis, Pfizer and UCB Pharma, Consultant of: Speaking fees from/consultant for AbbVie, Amgen, Biogen, BMS, Eli Lilly, Gilead, Janssen, MSD, Novartis, Pfizer and UCB Pharma, Grant/research support from: AbbVie, Eli Lilly, Novartis, Novo Nordisk and UCB Pharma, Richard B. Warren Consultant of: Consulting fees from AbbVie, Almirall, Amgen, Arena, Astellas, Avillion, Biogen, BMS, Boehringer Ingelheim, Celgene, Eli Lilly, GSK, Janssen, LEO Pharma, Novartis, Pfizer, Sanofi and UCB Pharma. Honoraria from Astellas, DiCE, GSK and Union, Grant/research support from: Research grants to his institution from AbbVie, Almirall, Janssen, LEO Pharma, Novartis, and UCB Pharma, Barbara Ink Shareholder of: UCB Pharma, AbbVie and GSK, Employee of: UCB Pharma, Rajan Bajracharya Shareholder of: UCB Pharma, Employee of: UCB Pharma, Jason Coarse Shareholder of: UCB Pharma, Employee of: UCB Pharma, Jason Eells Shareholder of: UCB Pharma, Employee of: UCB Pharma, Alice B Gottlieb Consultant of: Honoraria as an advisory board member, non-promotional speaker or consultant for Amgen, AnaptysBio, Avotres Therapeutics, BMS, Boehringer Ingelheim, Dermavant, DICE Therapeutics, Eli Lilly, Janssen, Novartis, Pfizer, Sanofi, Sun Pharma, UCB Pharma and Xbiotech (stock options for an RA project), Grant/research support from: AnaptysBio, BMS, Janssen, Novartis, Ortho Dermatologics, Sun Pharma and UCB Pharma; all funds go to the Icahn School of Medicine at Mount Sinai.