Abstract
BackgroundBimekizumab (BKZ) is a monoclonal IgG1 antibody that selectively inhibits IL-17F in addition to IL-17A.ObjectivesAssess BKZ efficacy and safety vs PBO in bDMARD-naïve pts with active PsA to Wk 24 of BE OPTIMAL.MethodsBE OPTIMAL (NCT03895203) comprises 16 wks double-blind PBO-controlled and 36 wks treatment-blind. Pts were ≥18 yrs, bDMARD-naïve, with adult-onset, active PsA, ≥3 tender and ≥3 swollen joints. Pts randomised 3:2:1, subcutaneous BKZ 160 mg Q4W:PBO:adalimumab (ADA; reference arm) 40 mg Q2W. From Wk 16, PBO pts received BKZ 160 mg Q4W. Primary endpoint: ACR50 at Wk 16.Results821/852 (96.4%) pts completed Wk 16 and 806 (94.6%) Wk 24. Mean age 48.7 yrs, BMI 29.2 kg/m2; since diagnosis: 5.9 yrs; 46.8% male. BL characteristics comparable across arms. Primary endpoint met (Wk 16 ACR50: 43.9% BKZ vs 10.0% PBO, p<0.001; ADA: 45.7%; Figure 1). All ranked secondary endpoints met at Wk 16 (Table 1). As early as Wk 2, ACR20 was higher in BKZ vs PBO (27.1% vs 7.8%, nominal p<0.001; ADA: 33.6%). Outcomes continued to improve at Wk 24 (Table 1). To Wk 16, pts with ≥1 TEAE, BKZ: 59.9%; PBO: 49.5%; ADA: 59.3%. SAE rate low (1.6%; 1.1%; 1.4%). Most frequent (≥5%) AEs for all arms: nasopharyngitis (9.3%; 4.6%; 5.0%), URTI (4.9%; 6.4%; 2.1%), increased ALT (0.7%; 0.7%; 5.0%). Candida infections: 2.6%, 0.7%, 0%; no systemic candidiasis. 2 malignancies (BKZ: basal cell carcinoma; PBO: breast cancer stage 1); no MACE, uveitis, IBD or deaths.Table 1.Wk 16 and 24 efficacyBLWk 16Wk 24PBO N=281BKZ 160 mg Q4W N=431ADA 40 mg Q2W N=140†PBO N=281BKZ 160 mg Q4W N=431ADA 40 mg Q2W N=140†p value (BKZ vs PBO)PBO→ BKZ 160 mg Q4WaN=281BKZ 160 mg Q4W N=431ADA 40 mg Q2W N=140†Ranked endpointsbACR50 [NRI],–––28189 (43.9)64<0.00110119666n (%)-10-45.7(35.9)(45.5)-47.1HAQ-DI CfB [MI],0.890.820.86−0.09 (0.03)−0.26 (0.02)−0.33<0.001c−0.28−0.30−0.34mean (SE)-0.04-0.03-0.05(0.04)(0.03)(0.02)(0.05)PASI90d [NRI],–––4133 (61.3)f28<0.00186 (61.4)e158 (72.8)f32n (%)(2.9)e(41.2)g(47.1)gSF-36 PCS CfB [MI],36.938.137.62.36.36.8<0.001c6.27.37.3mean (SE)-0.6-0.5-0.7-0.5-0.4-0.8-0.5-0.4-0.8MDA [NRI],51413719463<0.00110620967n (%)-1.8-3.2-0.7-13.2(45.0)-45(37.7)(48.5)-47.9vdHmTSS CfB (subgroup)h [MI], mean (SE)15.67 (1.80)i15.56 (1.69)j17.39 (2.89)k0.36 (0.10)i−0.01 (0.04)j−0.06 (0.08)k<0.001c–––vdHmTSS CfB [MI],mean (SE)13.31 (1.56)l13.44 (1.47)m14.55 (2.44)n0.31 (0.09)l0(0.04)m−0.03 (0.07)n0.001c–––Other endpointsACR20 [NRI],–––6726896<0.001o17528299n (%)-23.8(62.2)-68.6(62.3)(65.4)-70.7ACR70 [NRI],–––1210539<0.001o5312642n (%)-4.3(24.4)-27.9-18.9(29.2)-30PASI100d [NRI],–––3103f14<0.001o6012226n (%)(2.1)e(47.5)(20.6)g(42.9)e (56.2)f(38.2)gTJC CfB [MI],17.116.817.5−3.2−10.0−10.9<0.001o−9.4−11.5−11.8mean (SE)-0.7-0.6-1.1(0.7) (0.5)-1(0.7)(0.5)-0.9SJC CfB [MI],9.599.6−3.0 (0.5)−6.6 (0.3)−7.5<0.001o−6.8 (0.4)−7.2 (0.3)−7.9mean (SE)-0.4-0.3-0.6-0.6-0.6Randomised set. Interim results.†Reference arm; study not powered for statistical comparisons of ADA to BKZ or PBO.aPBO→BKZ pts received PBO to Wk 16, switched to BKZ 160 mg Q4W through Wk 24 (8 wks BKZ);bResolution of enthesitis/dactylitis in pts with LEI>0/LDI>0 at BL pooled with BE COMPLETE (Wk 16 LEI=0 BKZ: 124/249 [49.8%], PBO: 37/106 [34.9%], p=0.008; LDI=0 BKZ: 68/90 [75.6%], PBO: 24/47 [51.1%], p=0.002);cContinuous outcome p values calculated with RBMI data;dPts with PSO and ≥3% BSA at BL;en=140;fn=217;gn=68;hPts with hs-CRP ≥6 mg/L and/or bone erosion at BL;in=221;jn=357;kn=108;ln=261;mn=416;nn=131;oNominal, not powered for multiplicity.ConclusionDual inhibition of IL-17A and IL-17F with BKZ in bDMARD-naïve pts with active PsA resulted in rapid, clinically relevant improvements in musculoskeletal and skin outcomes vs PBO. No new safety signals observed.1,2References[1]Ritchlin CT Lancet 2020;395(10222):427–40; 2. Coates LC Ann Rheum Dis 2021;80:779–80(POS1022).Disclosure of InterestsIain McInnes Consultant of: AbbVie, BMS, Boehringer Ingelheim, Celgene, Eli Lilly, Janssen, Novartis, and UCB Pharma, Grant/research support from: BMS, Boehringer Ingelheim, Celgene, Janssen, UCB Pharma, Laura Coates Consultant of: AbbVie, Amgen, Boehringer Ingelheim, BMS, Celgene, Domain, Eli Lilly, Gilead, Galapagos, Janssen, Moonlake, Novartis, Pfizer, and UCB Pharma, Speakers bureau: AbbVie, Amgen, Biogen, Celgene, Eli Lilly, Galapagos, Gilead, GSK, Janssen, Medac, Novartis, Pfizer, and UCB Pharma, Grant/research support from: AbbVie, Amgen, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, and UCB Pharma, Robert B.M. Landewé Consultant of: Abbott, Ablynx, Amgen, AstraZeneca, BMS, Centocor, GSK, Novartis, Merck, Pfizer, Roche, Schering-Plough, UCB Pharma, and Wyeth, Speakers bureau: Abbott, Amgen, BMS, Centocor, Merck, Pfizer, Roche, Schering-Plough, UCB Pharma, and Wyeth, Grant/research support from: Abbott, Amgen, Centocor, Novartis, Pfizer, Roche, Schering-Plough, UCB Pharma, and Wyeth, Philip J Mease Consultant of: AbbVie, Amgen, BMS, Boehringer Ingelheim, Eli Lilly, Galapagos, Gilead, GSK, Janssen, Novartis, Pfizer, Sun Pharma and UCB Pharma, Speakers bureau: AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer and UCB Pharma, Grant/research support from: AbbVie, Amgen, BMS, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, Sun Pharma and UCB Pharma, Christopher T. Ritchlin Consultant of: AbbVie, Amgen, Eli Lilly, Gilead, Janssen, Novartis, Pfizer and UCB Pharma, Grant/research support from: AbbVie, Amgen and UCB Pharma, Yoshiya Tanaka Consultant of: AbbVie, Ayumi, Daiichi-Sankyo, Eli Lilly, GSK, Sanofi, and Taisho, Speakers bureau: AbbVie, Amgen, Astellas, AstraZeneca, BMS, Boehringer-Ingelheim, Chugai, Eisai, Eli Lilly, Gilead, Mitsubishi-Tanabe, and YL Biologics, Grant/research support from: AbbVie, Asahi-Kasei, Boehringer-Ingelheim, Chugai, Corrona, Daiichi-Sankyo, Eisai, Kowa, Mitsubishi-Tanabe, and Takeda, Akihiko Asahina Grant/research support from: AbbVie, Amgen, Eisai, Eli Lilly, Janssen, Kyowa Kirin, LEO Pharma, Maruho, Mitsubishi Tanabe Pharma, Pfizer, Sun Pharma, Taiho Pharma, Torii Pharmaceutical, and UCB Pharma, Laure Gossec Consultant of: AbbVie, Amgen, BMS, Celltrion, Galapagos, Gilead, GSK, Janssen, Lilly, Novartis, Pfizer and UCB Pharma, Grant/research support from: Amgen, Galapagos, Lilly, Pfizer, Sandoz and UCB Pharma, Alice B Gottlieb Consultant of: Amgen, AnaptsysBio, Avotres Therapeutics, Boehringer Ingelheim, BMS, Dermavant, Eli Lilly, Incyte, Janssen, Novartis, Pfizer, Sanofi, Sun Pharma, UCB Pharma, and XBiotech, Grant/research support from: Boehringer Ingelheim, Janssen, Novartis, Sun Pharma, UCB Pharma, and XBiotech: all funds go to Mount Sinai Medical School, Richard B. Warren Consultant of: AbbVie, Almirall, Amgen, Arena, Astellas, Avillion, Biogen, BMS, Boehringer Ingelheim, Celgene, Eli Lilly, GSK, Janssen, LEO Pharma, Novartis, Pfizer, Sanofi, and UCB Pharma, Paid instructor for: Astellas, DiCE, GSK, and Union, Grant/research support from: AbbVie, Almirall, Janssen, LEO Pharma, Novartis, and UCB Pharma, Barbara Ink Shareholder of: GSK, UCB Pharma, Employee of: UCB Pharma, Deepak Assudani Shareholder of: UCB Pharma, Employee of: UCB Pharma, Jason Coarse Shareholder of: UCB Pharma, Employee of: UCB Pharma, Rajan Bajracharya Shareholder of: UCB Pharma, Employee of: UCB Pharma, Joseph F. Merola Consultant of: AbbVie, Amgen, Biogen, BMS, Dermavant, Eli Lilly, Janssen, Leo Pharma, Novartis, Pfizer, Regeneron, Sanofi, Sun Pharma, and UCB Pharma, Paid instructor for: Amgen, Abbvie, Biogen, BMS, Dermavant, Eli Lilly, Janssen, Leo Pharma, Novartis, Pfizer, Regeneron, Sanofi, Sun Pharma, and UCB Pharma