L02: Bimekizumab Treatment in Biologic DMARD-Naïve Patients with Active Psoriatic Arthritis: 52-Week Efficacy and Safety Results from a Phase 3, Randomized, Placebo-Controlled, Active Reference Study
University of Rochester Medical Center Canandaigua, NY, United States
Christopher Ritchlin1, Laura Coates2, Iain McInnes3, Philip J. Mease4, Joseph Merola5, Yoshiya Tanaka6, Akihiko Asahina7, Laure Gossec8, Alice Gottlieb9, Diamant Thaci10, Barbara Ink11, Deepak Assudani11, Rajan Bajracharya11, Vish Shende11, Jason Coarse12 and Robert Landewé13, 1University of Rochester Medical Center, Rochester, NY, 2Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Diseases, University of Oxford and Oxford Biomedical Research Centre, Oxford University Hospitals NHS Trust, Oxford, United Kingdom, 3College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom, 4Swedish Medical Center/Providence St. Joseph Health and University of Washington School of Medicine, Seattle, WA, 5Harvard Medical School, Brigham and Women’s Hospital, Boston, MA, 6University of Occupational and Environmental Health Japan, Kitakyushu, Japan, 7Department of Dermatology, The Jikei University School of Medicine, Tokyo, Japan, 8Sorbonne Universités, UPMC Univ Paris 06, GRC-UPMC 08 (EEMOIS); AP-HP, Hôpital Pitié Salpêtrière, Rheumatology Department, Paris, France, Paris, France, 9Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY, 10Institute and Comprehensive Center for Inflammation Medicine, University of Lübeck, Lübeck, Germany, 11UCB Pharma, Slough, United Kingdom, 12UCB Pharma, Raleigh, NC, 13Amsterdam Rheumatology & Clinical Immunology Center, Amsterdam, and Zuyderland MC, Heerlen, Netherlands
Background/Purpose: Bimekizumab (BKZ) is a monoclonal IgG1 antibody that selectively inhibits IL-17F in addition to IL-17A. BKZ treatment has demonstrated superior efficacy in joints and skin versus placebo (PBO) at Week (Wk) 16 in the phase 3 BE OPTIMAL study in biologic DMARD (bDMARD)-naïve patients (pts) with active PsA.1 Wk 52 efficacy and safety data are presented here.
Methods: BE OPTIMAL (NCT03895203) comprised 16 wks double-blind, PBO-controlled, and 36 wks treatment-blind. bDMARD-naïve pts were eligible if they had adult-onset, active PsA meeting the Classification Criteria for PsA for ≥6 months, ≥3 tender and ≥3 swollen joints, and ≥1 active psoriatic lesion and/or history of psoriasis. Pts were randomized 3:2:1 subcutaneous BKZ 160 mg every 4 wks:PBO:reference arm (adalimumab [ADA] 40 mg every 2 wks). From Wk 16, PBO pts received BKZ 160 mg Q4W (PBO/BKZ). Missing data imputed using non-responder imputation (discrete) or multiple imputation (continuous).
Results: 821/852 (96.4%) pts completed Wk 16; 761 (89.3%) completed Wk 52. Baseline (BL) characteristics were generally balanced between groups (randomized set): mean age 48.7 years; BMI 29.2 kg/m2; time since diagnosis 5.9 years; 46.8% male; 49.9% had psoriasis affecting ≥3% body surface area (BSA).
At Wk 52, pts achieving ACR50: 53.0% PBO/BKZ, 54.5% BKZ, 50.0% ADA; pts with BL psoriasis (≥3% BSA) achieving complete skin clearance (Psoriasis Area and Severity Index [PASI]100): 65.0% PBO/BKZ, 60.8% BKZ, 48.5% ADA; pts achieving minimal disease activity: 53.7% PBO/BKZ, 55.0% BKZ, 52.9% ADA (Figure 1). Clinical joint and skin efficacy responses continued to increase or were sustained from Wk 16 to Wk 52 on BKZ; pts who switched to BKZ at Wk 16 demonstrated improvements in efficacy outcomes to Wk 52 (Table).
Overall radiographic progression was minimal to Wk 52. At Wk 52, pts with no radiographic progression (van der Heijde modified Total Sharp Score change from baseline ≤0.5): 87.3% PBO/BKZ, 89.3% BKZ, 94.1% ADA (radiographic set; observed case). Cumulative probability of radiographic progression is presented in Figure 2.
To Wk 52, 555/702 (79.1%) pts had ≥1 treatment-emergent adverse event (TEAE) while receiving BKZ; 113/140 (80.7%) on ADA. The three most frequent TEAEs on BKZ: nasopharyngitis (BKZ: 12.0% pts; ADA 8.6% pts), upper respiratory tract infection (BKZ: 7.1%; ADA: 5.7%), and urinary tract infection (BKZ: 6.1%; ADA: 3.6%). Pts who discontinued the study due to a TEAE: 21 (3.0%) BKZ; 7 (5.0%) ADA. Candida infections (high level term) reported in 7.7% BKZ, 0.7% ADA pts. All were mild/moderate; none systemic. 1 case of oral candidiasis led to discontinuation. To Wk 52, 3 BKZ‑treated pts had malignancies excluding non-melanoma skin cancers, 4 had adjudicated major adverse cardiac events, and 2 had definite IBD (ulcerative colitis); 1 death reported (motorcycle accident). No uveitis events were reported.
Conclusion: BKZ treatment demonstrated clinically meaningful improvements in efficacy outcomes in bDMARD-naïve pts with active PsA at Wk 16, which were sustained or continued to improve to Wk 52. BKZ was well tolerated; no new safety signals observed.2
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