The relative efficacy of bimekizumab and risankizumab in patients with PsA who were biologic disease-modifying anti-rheumatic drug naïve (bDMARD naïve) or with previous inadequate response or intolerance to tumor necrosis factor inhibitors (TNFi-IR) was assessed at 52 weeks (Wk52) using matching-adjusted indirect comparisons (MAIC). Relevant trials were systematically identified. For patients who were bDMARD naïve, individual patient data (IPD) from BE OPTIMAL (NCT03895203; N = 431) were matched with summary data from KEEPsAKE-1 (NCT03675308; N = 483). For patients who were TNFi-IR, IPD from BE COMPLETE (NCT03896581; N = 267) were matched with summary data from the TNFi-IR patient subgroup in KEEPsAKE-2 (NCT03671148; N = 106). To adjust for cross-trial differences, patients from the bimekizumab trials were re-weighted to match the baseline characteristics of patients in the risankizumab trials. Adjustment variables were selected based on expert consensus (n = 5) and adherence to established MAIC guidelines. Recalculated bimekizumab Wk52 outcomes for American College of Rheumatology (ACR) 20/50/70 response criteria and minimal disease activity (MDA) index (non-responder imputation) were compared with risankizumab outcomes via non-placebo-adjusted comparisons. In patients who were bDMARD naïve, bimekizumab had a significantly greater likelihood of response than risankizumab at Wk52 for ACR50 (odds ratio [95

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/m2, 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). 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.

Objectives. Evaluate effects of long-term bimekizumab treatment on patient-reported outcome (PRO) measures, symptoms and the impact of PsA on patients. Methods. Patients with active PsA were enrolled into BE ACTIVE, a 48-week randomised controlled trial (NCT02969525). After Week 48, patients could enter a 104-week open-label extension (NCT03347110), receiving bimekizumab 160 mg every four weeks. PRO measures assessed included arthritis pain visual analogue scale (VAS), PsA Impact of Disease (PsAID)-9, 36-Item Short Form Survey (SF-36) and HAQ-Disability Index (HAQ-Dl). Results were analysed as mean (S.E.M.) changes from baseline (CfB) from Week 0 to the end of the open-label extension (3years) and as percentage of patients reaching patient-acceptable symptom state (PASS) for global impact (PsAID-9 total score <= 4) and normal function (HAQ-DI total score <0.5). Non-responder imputation was applied to missing binary outcomes. Results. In 206 patients (mean age 49.3 years, 51.0% male), completion rate was high; 161 (78.2%) patients completed Week 152. Bimekizumab treatment was associated with long-term sustained improvements in pain [arthritis pain VAS CfB; Week 48: -29.9 (1.9); Week 152: -32.0 (1.9)] and fatigue [PsAID-9 fatigue CfB; -2.4 (0.2); -2.7 (0.2)]. High percentages of patients achieved acceptable symptom state (PsAID-9 PASS: 75.2%; 65.0%) and normalised function (HAQ-DI <0.5: 49.0%; 46.1%). Improvements in patient global assessment and SF-36 Physical Component Summary were also sustained. Conclusions. Bimekizumab treatment was associated with long-term sustained improvements in pain and fatigue, reducing overall impact of PsA on patients. Physical function and quality of life improved up to 3 years. [GRAPHICS] .

Abstract Background/Aims Bimekizumab (BKZ), a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)-17F and IL17A, has demonstrated an acceptable safety profile with improvements in joint and skin outcomes to 3 years in patients with active psoriatic arthritis (PsA). Psoriatic Arthritis Response Criteria (PsARC) response data can help relate clinical trial data to UK clinical practice. We report PsARC response rates to 3 years in patients with active PsA from the phase 2b 48-week (wk) dose-ranging study BE ACTIVE (NCT02969525) and its open-label extension (OLE)(NCT03347110). Methods In BE ACTIVE, patients were randomised (1:1:1:1:1) to placebo, BKZ 16mg, BKZ 160mg (with or without 320mg loading dose), or BKZ 320mg, every 4 wks (Q4W). At Wk12, patients assigned to placebo or BKZ 16mg were reassigned (1:1) to dose-blind BKZ 160mg or 320mg Q4W; other patients remained on their original dose. From Wk48 all patients received open-label BKZ 160mg Q4W. We report PsARC to Wk152 and maintenance of response among patients with PsARC response at Wk12, for the full analysis set (FAS). Data are reported as observed and with NRI. Results 206 patients were randomised at baseline in BE ACTIVE and included in the FAS. 181 patients entered the OLE and 161 completed the OLE. 157 patients had calculable PsARC response at Wk152. At Wk12, PsARC response (NRI) was achieved by 125/206, including placebo: 33.3% (14/42), BKZ 16mg: 56.1% (23/41), 160mg: 73.2% (60/82), 320mg: 68.3% (28/41) (Table). At Wk48 and Wk152, 78.2% (161/206) and 68.0% (140/206) patients were PsARC responders, respectively. Of the 125 PsARC responders at Wk12, 88.8% (111/125) also met PsARC at Wk48 and 74.4% (93/125) were PsARC responders at Wk152 (NRI). Over 152 wks, the exposure-adjusted incidence rate per 100 patient-years was 126.4 for all treatment-emergent adverse events (TEAEs), 4.1 for serious TEAEs, 0.7 for serious infections and 4.6 for Candida infections. Conclusion A numerically higher proportion of patients achieved PsARC response in all BKZ-treated groups at Wk12, compared with placebo. The PsARC response rate was sustained through 3 years. Nearly three-quarters of patients who achieved PsARC at Wk12 were also PsARC responders at Wk152. No new safety signals were observed. Disclosure W. Tillett: Consultancies; WT has received consulting fees from AbbVie, Amgen, Celgene, Eli Lilly, Janssen, MSD, Novartis, Pfizer and UCB Pharma. Honoraria; WT has received honoraria from AbbVie, Amgen, Celgene, Eli Lilly, Janssen, MSD, Novartis, Pfizer and UCB Pharma. Grants/research support; WT has received research grants from AbbVie, Amgen, Celgene, Eli Lilly, Janssen, MSD, Novartis, Pfizer and UCB Pharma. I.B. McInnes: Consultancies; IBM has received consulting fees from AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, UCB Pharma. Honoraria; IBM has received honoraria from AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, UCB Pharma. Grants/research support; IBM has received research support from Boehringer Ingelheim, BMS, Celgene, Janssen and UCB Pharma. D. McGonagle: Consultancies; DM has received consulting fees from AbbVie, Celgene, Janssen, Merck, Novartis, Pfizer and UCB Pharma. Honoraria; DM has received honoraria from AbbVie, Celgene, Janssen, Merck, Novartis, Pfizer and UCB Pharma. Member of speakers’ bureau; DM has been on speaker’s bureau for AbbVie, Celgene, Janssen, Merck, Novartis, Pfizer and UCB Pharma. Grants/research support; DM has received grants/research support from AbbVie, Celgene, Janssen, Merck, Pfizer and Novartis. D.R. Jadon: Consultancies; DRJ has received consultancy fees from AbbVie, Amgen, Biogen, BMS, Celgene, Celltrion, Eli Lilly, Fresenius Kabi, Galapagos, GSK, Janssen, Merck, Novartis, Pfizer, Roche, Sandoz, Sanofi and UCB Pharma. Grants/research support; DRJ has received research grants from AbbVie, Amgen, Biogen, BMS, Celgene, Celltrion, Eli Lilly, Fresenius Kabi, Galapagos, GSK, Janssen, Merck, Novartis, Pfizer, Roche, Sandoz, Sanofi, UCB Pharma. B. Ink: Corporate appointments; BI is an employee of UCB Pharma. Shareholder/stock ownership; BI is a shareholder of GSK and UCB Pharma. D. Assudani: Corporate appointments; DA is an employee of UCB Pharma. Shareholder/stock ownership; DA is a shareholder of UCB Pharma. J. Coarse: Corporate appointments; JC is an employee of UCB Pharma. Shareholder/stock ownership; JC is a shareholder of UCB Pharma. J. Eells: Corporate appointments; JE is an employee of UCB Pharma. Shareholder/stock ownership; JE is a shareholder of UCB Pharma. L.C. Coates: Consultancies; LCC has received consulting fees from AbbVie, Amgen, Biogen, Boehringer Ingelheim, Celgene, Domain, Eli Lilly, Gilead and Janssen. Member of speakers’ bureau; LCC has been on speaker’s bureau for AbbVie, Amgen, Biogen, Celgene, Eli Lilly, Gilead, GSK, Janssen, Medac, Novartis, Pfizer and UCB Pharma. Grants/research support; LCC has received grants/research support from AbbVie, Amgen, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer and UCB Pharma.

Introduction: Bimekizumab (BKZ), a monoclonal antibody that selectively inhibits interleukin (IL)-17F in addition to IL17A, has demonstrated clinical improvements in joint and skin outcomes in patients with active psoriatic arthritis (PsA). Most patients achieving high thresholds of disease control at Week 12 of BE ACTIVE (NCT02969525) maintained this response through 2 years in the open-label extension (OLE, NCT03347110). We report maintenance of response through 3 years of bimekizumab treatment.