Bimekizumab treatment in biologic DMARD-naïve patients with active psoriatic arthritis: 52-week efficacy and safety results from the phase III, randomised, placebo-controlled, active reference BE OPTIMAL study

Abstract

Objectives: Bimekizumab (BKZ) is a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)-17F in addition to IL-17A. BKZ treatment has demonstrated superior efficacy versus placebo (PBO) at Week 16 in biologic disease-modifying antirheumatic drug (DMARD)-naïve patients with active psoriatic arthritis (PsA). Here, we report long-term efficacy and safety to Week 52.

Methods: BE OPTIMAL comprised a 16-week, double-blind, PBO-controlled period, then 36 weeks treatment-blind. Patients were randomised 3:2:1 to subcutaneous BKZ 160 mg every 4 weeks, PBO with switch to BKZ at Week 16, or reference arm (adalimumab (ADA) 40 mg every 2 weeks). Efficacy outcomes included the American College of Rheumatology (ACR) response criteria 20/50/70, Psoriasis Area and Severity Index (PASI) 75/90/100 in patients with baseline psoriasis affecting ≥3% body surface area and minimal disease activity (MDA); non-responder imputation.

Results: ACR20/50/70, PASI75/90/100 and MDA responses were sustained with BKZ to Week 52, consistent with results observed at Week 16. Patients who switched to BKZ at Week 16 demonstrated improvements in efficacy with similar results to BKZ-randomised patients by Week 52.To Week 52, 555/702 (79.1%) patients had ≥1 treatment-emergent adverse event (TEAE) during BKZ treatment; 113/140 (80.7%) on ADA. On BKZ, 46 (6.6%) patients had serious TEAEs. 54 (7.7%) Candida infections occurred during BKZ treatment and 1 (0.7%) during ADA; all cases were localised and non-serious. One death occurred in a BKZ-treated patient, unrelated to treatment.

Conclusions: The efficacy of BKZ in bDMARD-naïve patients with PsA was sustained from Week 16 to Week 52. BKZ was well tolerated with no new safety signals observed.

Trial registration number: NCT03895203.

Keywords: arthritis, psoriatic; biological therapy; psoriatic arthritis.

Conflict of interest statement

Competing interests: CTR: research for AbbVie; consultant for Amgen, AbbVie, Eli Lilly, Gilead, Janssen, Novartis, Pfizer and UCB Pharma. LCC: has received grants/research support from AbbVie, Amgen, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer and UCB Pharma; worked as a paid consultant for AbbVie, Amgen, BMS, Boehringer Ingelheim, Celgene, Domain, Eli Lilly, Galapagos, Gilead, Janssen, Moonlake, Novartis, Pfizer and UCB Pharma; and has been paid as a speaker for AbbVie, Amgen, Biogen, Celgene, Eli Lilly, Galapagos, Gilead, GSK, Janssen, Medac, Novartis, Pfizer and UCB Pharma. IBM: consulting fees and honoraria from AbbVie, AstraZeneca, BMS, Boehringer Ingelheim, Cabaletta, Causeway Therapeutics, Celgene, Eli Lilly, Evelo, Janssen, Moonlake, Novartis and UCB Pharma; research support from BMS, Boehringer Ingelheim, Celgene, Janssen, Novartis and UCB Pharma; Associate Editor at Annals of the Rheumatic Diseases. PJM: research grants from AbbVie, Amgen, BMS, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, Sun Pharma and UCB Pharma; consultancy fees from AbbVie, Acelyrin, Aclaris, Amgen, BMS, Boehringer Ingelheim, Eli Lilly, Galapagos, Gilead, GSK, Janssen, Moonlake Pharma, Novartis, Pfizer, Sun Pharma and UCB Pharma; speakers’ bureau from AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer and UCB Pharma. JFM: consultant and/or investigator for AbbVie, Amgen, Biogen, BMS, Dermavant, Eli Lilly, Janssen, LEO Pharma, Novartis, Pfizer, Regeneron, Sanofi, Sun Pharma and UCB Pharma. YT: speaking fees and/or honoraria from AbbVie, AstraZeneca, BMS, Boehringer Ingelheim, Chugai, Eisai, Eli Lilly, Gilead, GSK, Pfizer, Taiho and Taisho; received grants from Chugai, Eisai, Mitsubishi-Tanabe and Taisho; Editorial Board Member at Annals of the Rheumatic Diseases. AA: honoraria and/or research grants from AbbVie, Amgen, BMS, Boehringer Ingelheim, Eisai, Eli Lilly, Janssen, Kyowa Kirin, LEO Pharma, Maruho, Mitsubishi Tanabe Pharma, Novartis, Pfizer, Sun Pharma, Taiho Pharma, Torii Pharmaceutical and UCB Pharma. LG: research grants from Sandoz and UCB Pharma; consulting fees from AbbVie, Amgen, BMS, Celltrion, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Pfizer, Sandoz and UCB Pharma; Editorial Board Member at Annals of the Rheumatic Diseases. ABG: received honoraria as an advisory board member and consultant for Amgen, AnaptypsBio, Avotres Therapeutics, BMS, Boehringer Ingelheim, Dice Therapeutics, Eli Lilly, Janssen, Novartis, Sanofi, UCB Pharma and Xbiotech; has received research/educational grants from AnaptypsBio, BMS, Moonlake Immunotherapeutics, Novartis and UCB Pharma (all paid to Mount Sinai School of Medicine). RBW: 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; research grants to his institution from AbbVie, Almirall, Janssen, LEO Pharma, Novartis and UCB Pharma; honoraria from Astellas, DiCE, GSK and Union. BI: employee of UCB Pharma and shareholder of AbbVie, GSK and UCB Pharma. RB, VS, JC are all employees and shareholders of UCB Pharma. RL: consultancy fees from AbbVie, AstraZeneca, BMS, Eli Lilly, Novartis, Pfizer and UCB Pharma. Research grants from AbbVie, Novartis, Pfizer and UCB Pharma. Owner of Rheumatology Consultancy BV, an AMS company under Dutch law; Editorial Board Member at Annals of the Rheumatic Diseases.

© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1

Patient disposition. The percentage of patients completing or not completing treatment periods is calculated with the initial number of patients who were randomised to that group. Completed not on randomised treatment refers to patients that stopped treatment but continued in the study. ADA, adalimumab; BKZ, bimekizumab; Q2W, every 2 weeks; Q4W, every 4 weeks.

Figure 2

ACR responders to Week 52. Randomised set. P value was calculated using a logistic regression model with treatment, bone erosion at baseline and region as stratification factors. The study was not powered for statistical comparisons of ADA with BKZ or PBO. All data points can be found in table format in online supplemental table 5. *ACR50 at Week 16 was the primary end point. ACR20/50/70, American College of Rheumatology response criteria ≥20%/50%/70% improvement; ADA, adalimumab; BKZ, bimekizumab; NRI, non-responder imputation; OC, observed case; PBO, placebo; Q2W, every 2 weeks; Q4W, every 4 weeks.

Figure 3

PASI responders to Week 52. Randomised set, in patients with psoriasis affecting ≥3% BSA at baseline. P value was calculated using a logistic regression model with treatment, bone erosion at baseline and region as stratification factors. The study was not powered for statistical comparisons of ADA with BKZ or PBO. All data points can be found in table format in online supplemental table 6. *PASI90 was a ranked secondary end point. ADA, adalimumab; BKZ, bimekizumab; BSA, body surface area; NRI, non-responder imputation; OC, observed case; PASI75/90/100, Psoriasis Area and Severity Index ≥75%/90%/100% improvement; PBO, placebo; Q2W, every 2 weeks; Q4W, every 4 weeks.

Figure 4

Additional efficacy end points. Randomised set. P value was calculated using a logistic regression model with treatment, bone erosion at baseline and region as stratification factors. The study was not powered for statistical comparisons of ADA with BKZ or PBO. All data points can be found in table format in online supplemental table 7. *MDA was a ranked secondary end point; †In patients with psoriasis affecting ≥3% BSA at baseline; PBO/BKZ: n=140; BKZ: n=217; ADA: n=68. ACR50, American College of Rheumatology response criteria ≥50% improvement; ADA, adalimumab; BKZ, bimekizumab; BSA, body surface area; MDA, minimal disease activity; NRI, non-responder imputation; OC, observed case; PASI100, Psoriasis Area and Severity Index 100% improvement; PBO, placebo; Q2W, every 2 weeks; Q4W, every 4 weeks; VLDA, very low disease activity.