Safety and Efficacy of Bimekizumab in Patients with Psoriatic Arthritis: 2-Year Results from Two Phase 3 Studies

Abstract

Introduction: Psoriatic arthritis (PsA) is a chronic inflammatory disease requiring long-term treatment. Bimekizumab, a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)-17F in addition to IL-17A, has demonstrated tolerability and sustained clinical efficacy for up to 1 year for patients with PsA. Here, we report the longer-‍term safety and efficacy of bimekizumab up to 2 years.

Methods: BE OPTIMAL (biologic disease-modifying antirheumatic drug [bDMARD]-naïve) and BE COMPLETE (prior inadequate response/intolerance to tumor necrosis factor inhibitors [TNFi-IR]) assessed subcutaneous bimekizumab 160 mg every 4 weeks in patients with PsA. BE OPTIMAL included a reference arm (adalimumab 40 mg every 2 weeks); patients switched to bimekizumab at week 52 with no washout between treatments. BE OPTIMAL week 52 and BE COMPLETE week 16 completers were eligible for the BE VITAL open-label extension. Efficacy outcomes are reported to week 104/100 (BE OPTIMAL/BE COMPLETE).

Results: A total of 710/852 (83.3%) bDMARD-naïve and 322/400 (80.5%) TNFi-IR patients completed week 104/100. Up to 104 weeks, patients treated with bimekizumab in BE OPTIMAL and BE COMPLETE had treatment-emergent adverse event incidence rates (exposure-adjusted incidence rate/100 patient-years) of 179.9 (95% CI 166.9, 193.7) and 100.3 (89.2, ‍112.4), respectively. The proportion of patients achieving efficacy outcomes (≥ 50% improvement from baseline in American College of Rheumatology [ACR] response criteria, 100% improvement from baseline in Psorisis Area and Severity Index [PASI], minimal disease activity [MDA]) was sustained in all patients from week 52 to week 104/100.

Conclusions: Bimekizumab was well tolerated for up to 2 years of treatment and no new safety signals were observed. Sustained clinical efficacy was observed up to 2 years in bDMARD-naïve and TNFi-IR patients with active PsA. Patients switching from adalimumab to bimekizumab demonstrated further improvement in skin and nail symptoms, and sustained efficacy in joint symptoms.

Trial registration: BE OPTIMAL (NCT03895203), BE COMPLETE (NCT03896581), BE VITAL (NCT04009499).

Keywords: Bimekizumab; Efficacy; Psoriatic arthritis; Safety; TNFi-‍inadequate responders; bDMARD-naïve.

Fig. 1

BE OPTIMAL and BE COMPLETE study designs. The ADA 40 mg Q2W treatment arm served as an active reference. The BE OPTIMAL study was not powered for statistical comparisons of ADA to BKZ or PBO. Completion rates include patients that completed to week 52/104 in BE OPTIMAL and week 52/100 in BE COMPLETE not on randomized treatment (BE OPTIMAL week 52: 9 [1.1%], week 104: 8 [0.9%]; BE COMPLETE week 52: 4 [1.0%], week 100: 2 [0.5%]). 2 patients in BE COMPLETE were classified as ongoing at week 52 as they did not have a visit for week 52 but no formal discontinuation reason was reported. ACR50‍ ≥ 50% improvement in American College of Rheumatology response criteria, ADA ‍adalimumab, bDMARD biologic disease-‍modifying antirheumatic drug, BKZ bimekizumab, OLE open-label extension, PBO placebo, TNFi-IR prior inadequate response or intolerance to tumor necrosis factor inhibitors

Fig. 2

ACR20/50/70 responses to week 104/100 (NRI, OC). Randomized Set. In BE OPTIMAL, patients randomized to ADA at baseline switched to BKZ 160 mg Q4W at week 52. ^aReference arm; study not powered for statistical comparisons between ADA and BKZ or PBO. ACR20/50/70 ‍ ≥ 20/50/70% improvement from baseline in American College of Rheumatology response criteria, ADA ‍adalimumab, bDMARD biologic disease-modifying antirheumatic drug, BKZ‍ bimekizumab, NRI ‍non-responder imputation, OC observed case, PBO placebo, Q4W ‍every 4 weeks, TNFi-IR prior inadequate response or intolerance to tumor necrosis factor inhibitors

Fig. 3

PASI75/90/100 responses to week 104/100 (NRI, OC). Randomized Set, in patients with ≥ 3% body surface area affected by psoriasis at baseline. In BE OPTIMAL, patients randomized to ADA at baseline switched to BKZ 160 mg Q4W at week 52. ^aReference arm; study not powered for statistical comparisons between ADA and BKZ or PBO. ADA adalimumab, bDMARD biologic disease-modifying antirheumatic drug, BKZ bimekizumab, NRI‍ non-responder imputation, OC ‍observed case, PASI75/90/100‍ ≥ 75/90/100% improvement from baseline in Psoriasis Area and Severity Index, PBO placebo, Q4W every 4 weeks, TNFi-‍IR prior inadequate response or intolerance to tumor necrosis factor inhibitors

Fig. 4

MDA, VLDA and ACR50 + PASI100 responses to week 104/100 (NRI, OC). Randomized Set. In BE OPTIMAL, patients randomized to ADA at baseline switched to BKZ 160 mg Q4W at week 52. ^aIn patients with  ≥ 3% body surface area affected by psoriasis at baseline. BE OPTIMAL: 140 PBO/BKZ, 217 BKZ, 68 ADA/BKZ; BE COMPLETE: 88 PBO/BKZ, 176 BKZ; ^bReference arm; study not powered for statistical comparisons between ADA and BKZ or PBO. ACR50 + PASI100 Achievement of both ≥ 50% improvement in American College of Rheumatology response criteria and 100% improvement in Psoriasis Area and Severity Index; ADA adalimumab, bDMARD‍ biologic disease-‍modifying antirheumatic drug, BKZ bimekizumab, MDA ‍minimal disease activity, NRI ‍non-‍responder imputation, OC observed case, PBO placebo, Q4W every 4 weeks, TNFi-IR prior inadequate response or intolerance to tumor necrosis factor inhibitors, VLDA ‍very low disease activity

Fig. 5

SJC (I) and TJC (II) resolution and change from baseline to week 104/100. Randomized Set. In BE OPTIMAL, patients randomized to ADA at baseline switched to BKZ 160 mg Q4W at week 52. Error bars represent standard errors. ^aReference arm; study not powered for statistical comparisons between ADA and BKZ or PBO. ADA adalimumab, bDMARD‍ biologic disease-modifying antirheumatic drug, BKZ‍ bimekizumab, CfB change from baseline, MI ‍multiple imputation, NRI non-responder imputation, OC observed case, PBO placebo, Q4W every 4 weeks, SD standard deviation, SJC swollen joint count, TJC tender joint count, TNFi-‍‍‍‍IR‍ prior inadequate response or intolerance to tumor necrosis factor inhibitors

Fig. 6

Enthesitis, dactylitis and nail psoriasis resolution to week 104/100 (NRI, OC). Randomized Set. In BE OPTIMAL, patients randomized to ADA at baseline switched to BKZ 160 mg Q4W at week 52. ^aIn patients with enthesitis at baseline (LEI > 0; BE OPTIMAL: 70 PBO/BKZ, 143 BKZ, 36 ADA/BKZ; BE COMPLETE: 36 PBO/BKZ, 106 BKZ); ^bIn patients with dactylitis at baseline (LDI > 0; BE OPTIMAL:‍ 33 PBO/BKZ, 56 BKZ, 11 ADA/BKZ; BE COMPLETE: 14 PBO/BKZ, 34 BKZ); ^cIn patients with nail psoriasis at baseline (mNAPSI > 0; BE OPTIMAL: 156 PBO/BKZ, 244 BKZ, 75 ADA/BKZ; BE COMPLETE: 83 PBO/BKZ, 159 BKZ); ^dReference arm; study not powered for statistical comparisons between ADA and BKZ or PBO. ADA adalimumab, bDMARD‍ biologic disease-modifying antirheumatic drug, BKZ‍ bimekizumab, LDI Leeds Dactylitis Index, LEI Leeds Enthesitis Index, mNAPSI modified Nail Psoriasis Severity Index, NRI non-‍responder imputation, OC observed case, PBO‍ placebo, Q4W every 4 weeks, TNFi-‍IR‍ prior inadequate response or intolerance to tumor necrosis factor inhibitors