Search

Objectives: To evaluate 1-year bimekizumab efficacy in PsA from the patient perspective using the 12-item PsA Impact of Disease (PsAID-12) questionnaire., Methods: BE OPTIMAL (NCT03895203; biologic DMARD [bDMARD]-naïve), BE COMPLETE (NCT03896581; inadequate response/intolerance to TNF inhibitors [TNFi-IR]) and BE VITAL (NCT04009499; open-label extension) assessed bimekizumab 160 mg every 4 weeks in patients with PsA. Post hoc analyses of patient-reported disease impact, assessed by the PsAID-12 questionnaire, are reported to 1 year (collected to Week 40 in BE COMPLETE)., Results: Overall, 1,112 total patients were included (698 bimekizumab, 414 placebo). Rapid improvements observed with bimekizumab treatment at Week 4 continued to Week 16 and were sustained to 1 year. At 1 year, mean (SE) change from baseline in PsAID-12 total score was comparable between bimekizumab-randomized patients and patients who switched to bimekizumab at Week 16 (bDMARD-naïve bimekizumab -2.3 [0.1], placebo/bimekizumab -2.2 [0.1]; TNFi-IR bimekizumab -2.5 [0.1], placebo/bimekizumab -2.2 [0.2]). Proportions of bimekizumab-randomized patients achieving clinically meaningful within-patient improvement (≥3-point decrease from baseline) at Week 16 were sustained to 1 year (bDMARD-naïve 49.0%; TNFi-IR 48.5%) and were similar for placebo/bimekizumab patients (bDMARD-naïve 44.4%; TNFi-IR 40.6%). Across studies and arms, 35.3% to 47.8% of patients had minimal or no symptom impact at 1 year. Improvements were observed to 1 year across all single-item domains, including pain, fatigue and skin problems., Conclusion: Bimekizumab treatment resulted in rapid and sustained clinically meaningful improvements in disease impact up to 1 year in bDMARD-naïve and TNFi-IR patients with PsA., Trial Registration: BE OPTIMAL: NCT03895203; BE COMPLETE: NCT03896581; BE VITAL: NCT04009499 (ClinicalTrials.gov)., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

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)., (© 2024. The Author(s).)

Objective: The objective of this study was to assess 52-week efficacy and safety of bimekizumab in patients with active psoriatic arthritis (PsA) with or without concomitant methotrexate (+/-MTX) treatment at baseline., Methods: We conducted a post hoc analysis of patients in BE OPTIMAL (NCT03895203; biologic disease-modifying antirheumatic drug [bDMARD]-naïve), BE COMPLETE (NCT03896581; prior inadequate response or intolerance to tumor necrosis factor inhibitors [TNFi-IR]), and the BE VITAL open-label extension (NCT04009499) study. Patients were randomized to one of the following treatment groups: bimekizumab 160 mg every four weeks, placebo, or a reference drug (adalimumab 40 mg every two weeks; BE OPTIMAL only). From Week 16, placebo-randomized patients received bimekizumab. Missing data were imputed using non-responder imputation, multiple imputation, or worst-category imputation., Results: Through Week 52, similar proportions of bimekizumab-treated patients achieved American College of Rheumatology 50% (ACR50) response criteria for both +MTX and -MTX (BE OPTIMAL: 54.4% +MTX, 54.7% -MTX; BE COMPLETE: 56.3% +MTX, 48.0% -MTX). Similar proportions of bimekizumab-treated patients achieved complete skin clearance (Psoriasis Area and Severity Index 100% [PASI100] response) and minimal disease activity in both +MTX and -MTX groups. Similar trends were seen in placebo/bimekizumab-treated patients. Through Week 52, the proportion of bimekizumab-treated patients with ≥1 treatment-emergent adverse event were similar between the +MTX and -MTX groups (BE OPTIMAL 325 of 410 [79.3%] vs 230 of 292 [78.8%], BE COMPLETE 105 of 168 [62.5%] vs 138 of 220 [62.7%]). The safety profile was comparable between subgroups and consistent with the prior safety profile of bimekizumab., Conclusion: Treatment with bimekizumab demonstrated consistent, sustained efficacy to 52 weeks in bDMARD-naïve and TNFi-IR patients with PsA and was well tolerated, irrespective of concomitant MTX., (© 2024 UCB Pharma and The Author(s). ACR Open Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Objectives: To assess 52-week safety and efficacy of bimekizumab in patients with active psoriatic arthritis (PsA) and prior inadequate response/intolerance to tumour necrosis factor inhibitors., Methods: Patients completing the 16-week phase III double-blind, placebo-controlled BE COMPLETE (NCT03896581) study entered the open-label extension, BE VITAL (NCT04009499). All patients in BE VITAL received 160 mg bimekizumab every 4 weeks. Safety and efficacy are reported to week 52., Results: A total of 347/400 (86.8%) patients completed week 52. To week 52, the exposure-adjusted incidence rate/100 patient-years for ≥1 treatment-emergent adverse event (TEAE) was 126.0, and was 7.0 for serious TEAEs. The most frequent TEAEs were SARS-CoV-2 (COVID-19), oral candidiasis, nasopharyngitis and urinary tract infection. All fungal infections were mild or moderate in severity and localised; two patients discontinued the study due to oral candidiasis. No cases of active tuberculosis, uveitis or inflammatory bowel disease were reported. One sudden death occurred. Sustained efficacy was observed with bimekizumab from week 16 to ‍52 across clinical and patient-reported outcomes. At week 52, 51.7% bimekizumab-randomised and 40.6% placebo/bimekizumab patients (receiving bimekizumab from week 16 to 52) had ≥50% improvement in the American College of Rheumatology criteria. Complete skin clearance (Psoriasis Area and Severity Index 100) was achieved by 65.9% bimekizumab and 60.2% placebo/bimekizumab patients at week 52. Minimal disease activity was achieved by 47.2% bimekizumab and 33.1% placebo/bimekizumab patients at week 52., Conclusions: Bimekizumab demonstrated a safety profile consistent with previous reports; no new safety signals were identified. Sustained efficacy was observed from week 16 to 52., Competing Interests: Competing interests: LCC: Grants/research support from AbbVie, Amgen, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer and UCB Pharma; consultant for AbbVie, Amgen, BMS, Boehringer Ingelheim, Celgene, Domain, Eli Lilly, Galapagos, Gilead, Janssen, Moonlake Pharma, Novartis, Pfizer and UCB Pharma; speaking fees from AbbVie, Amgen, Biogen, Celgene, Eli Lilly, Galapagos, Gilead, GSK, Janssen, medac, Novartis, Pfizer and UCB Pharma. Associate Editor of RMD Open. RL: Consultancy fees from AbbVie, AstraZeneca, BMS, Eli Lilly, Novartis, Pfizer and UCB Pharma; research grants from AbbVie, Pfizer, Novartis, and UCB Pharma; owner of Rheumatology Consultancy BV, an AMS company under Dutch law. On the Editorial Board of RMD Open. IBM: Consulting fees and honoraria from AbbVie, AstraZeneca, BMS, Boehringer Ingelheim, Cabaletta, Causeway Therapeutics, Celgene, Eli Lilly, Evelo, Janssen, Moonlake Pharma, Novartis and UCB Pharma; research support from BMS, Boehringer Ingelheim, Celgene, Janssen, Novartis and UCB Pharma. On the Editorial Board of RMD Open. 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 for AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer and UCB Pharma. CTR: Research for AbbVie; consultant for AbbVie, Amgen, Eli Lilly, Gilead, Janssen, Novartis, Pfizer 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. On the Editorial Board of RMD Open. 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 Co. and UCB Pharma. FB: Consultant and/or speaker and/or investigator for AbbVie, Affibody, Amgen, BMS, Boehringer Ingelheim, Celgene, Chugai, Eli Lilly, Genzyme, GSK, Janssen, MoonLake Pharma, MSD, Novartis, Pfizer, Roche, Sandoz and Sanofi. DDG: Consultant and/or received grant support from AbbVie, Amgen, BMS, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer and UCB Pharma. LG: Grants from AbbVie, Biogen, Eli Lilly, Novartis, Sandoz and UCB Pharma; personal fees from AbbVie, Amgen, BMS, Celltrion, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Pfizer, Sandoz and UCB Pharma. AMO: Research grants to Johns Hopkins University from AbbVie, Amgen, and Janssen; consulting fees from BMS, Janssen, Sanofi and UCB Pharma. ABG: Received research/educational grants from AnaptypsBio, BMS, Highlights Therapeutics, Janssen, Moonlake Immunotherapeutics AG, Novartis and UCB Pharma, (all paid to Mount Sinai School of Medicine); Received honoraria as an advisory board member and consultant for Amgen, AnaptypsBio, Avotres Therapeutics, BMS, Boehringer Ingelheim, Dice Therapeutics, Eli Lilly, Highlights Therapeutics, Janssen, Novartis, Sanofi, UCB and Xbiotech. 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 Therapeutics, GSK and Union Therapeutics. BI: Shareholder of AbbVie, GSK and UCB Pharma; employee of UCB Pharma. RB and JC: Employees and shareholders of UCB Pharma. VS: Employee of UCB Pharma. JFM: Consultant and/or investigator for AbbVie, Amgen, Biogen, BMS, Dermavant, Eli Lilly, Janssen, LEO Pharma, Pfizer, Novartis, Regeneron, Sanofi, Sun Pharma and UCB Pharma., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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., Competing Interests: 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.)

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-DI). Results were analysed as mean (S.E.M.) changes from baseline (CfB) from Week 0 to the end of the open-label extension (3 years) 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., Trial Registration: ClinicalTrials.gov, https://clinicaltrials.gov, NCT02969525, NCT03347110., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Background: Bimekizumab is a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)-17A and IL-17F. We assessed the efficacy and safety of bimekizumab in patients with active psoriatic arthritis who were naive to biologic disease-modifying antirheumatic drugs (DMARDs)., Methods: BE OPTIMAL was a 52-week, phase 3, multicentre, randomised, double-blind, placebo-controlled, active reference (adalimumab) trial done at 135 sites (hospitals, clinics, doctors' offices, and research centres) in 14 countries. Eligible patients were 18 years or older with a documented diagnosis of adult-onset psoriatic arthritis that met the Classification Criteria for Psoriatic Arthritis for at least 6 months before screening. Participants were randomly assigned with an interactive-voice and web-response system on the basis of a predetermined randomisation schedule (3:2:1, stratified by region and bone erosion number at baseline) to bimekizumab 160 mg every 4 weeks, placebo every 2 weeks, or the reference group (adalimumab 40 mg every 2 weeks), all administered subcutaneously. At week 16, patients randomly assigned to placebo switched to bimekizumab 160 mg every 4 weeks. The primary endpoint was the proportion of patients reaching 50% or greater improvement in American College of Rheumatology criteria (ACR50) at week 16 (non-responder imputation). Efficacy analyses included all patients who were randomly assigned (intention-to-treat population); the safety analysis set comprised patients who received one or more doses of treatment. Data are presented to week 24 (preplanned analysis). This trial is registered at ClinicalTrials.gov, NCT03895203., Findings: Between April 3, 2019, and Oct 25, 2021, 1163 patients were screened and 852 were randomly assigned to bimekizumab (n=431), placebo (n=281), and reference (adalimumab; n=140) groups. At week 16, significantly more patients receiving bimekizumab (189 [44%] of 431) reached ACR50 response versus placebo (28 [10%] of 281; odds ratio 7·1 [95% CI 4·6-10·9], p<0·0001; adalimumab 64 [46%] of 140). All secondary hierarchical endpoints were met. Treatment-emergent adverse events up to week 16 were reported in 258 [60%] of 431 patients receiving bimekizumab, 139 [49%] of 281 patients receiving placebo, and 83 [59%] of 140 patients receiving adalimumab. No deaths occurred., Interpretation: Bimekizumab treatment had superior improvements in joint, skin, and radiographic efficacy outcomes at week 16 compared with placebo in patients with psoriatic arthritis who were naive to biologic DMARDs. The safety profile of bimekizumab, including the occurrence of fungal infections, was consistent with previous phase 3 studies in patients with plaque psoriasis, and with IL-17A inhibitors., Funding: UCB Pharma., Competing Interests: Declaration of interests IBM reports consulting fees and honoraria from AbbVie, AstraZeneca, BMS, Boehringer Ingelheim, Cabaletta, Causeway Therapeutics, Celgene, Evelo, Janssen, Novartis, Lilly, Moonlake, and UCB Pharma; and research support from BMS, Boehringer Ingelheim, Celgene, Janssen, Novartis, and UCB Pharma. AA reports honoraria or research grants from AbbVie, Amgen, BMS, Boehringer Ingelheim, Eisai, Eli Lilly, Janssen, Kyowa Kirin, LEO Pharma, Maruho, Mitsubishi Tanabe Pharma, Pfizer, Sun Pharma, Taiho Pharma, Torii Pharmaceutical, and UCB Pharma. LCC reports grants or research support from AbbVie, Amgen, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, and UCB Pharma; paid consultant work for AbbVie, Amgen, BMS, Boehringer Ingelheim, Celgene, Domain, Eli Lilly, Gilead, Galapagos, Janssen, Moonlake, Novartis, Pfizer, and UCB Pharma; and paid speaker work for AbbVie, Amgen, Biogen, Celgene, Eli Lilly, Galapagos, Gilead, GSK, Janssen, Medac, Novartis, Pfizer, and UCB Pharma. RL reports consultancy fees from AbbVie, AstraZeneca, BMS, Eli Lilly, Novartis, Pfizer, and UCB Pharma; research grants from AbbVie, Novartis, Pfizer, and UCB Pharma; and is an owner of Rheumatology Consultancy, an AMS company under Dutch law. JFM reports consultant or investigator work for AbbVie, Amgen, Biogen, BMS, Dermavant, Eli Lilly, Janssen, LEO Pharma, Novartis, Pfizer, Regeneron, Sanofi, Sun Pharma, and UCB Pharma. CTR reports research for AbbVie, Amgen, and UCB Pharma; and consultancy for Amgen, AbbVie, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, and UCB Pharma. YT reports speaking fees or honoraria from AbbVie, AstraZeneca, BMS, Boehringer Ingelheim, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, GSK, Mitsubishi-Tanabe, and Pfizer; and research grants from AbbVie, Asahi-Kasei, Boehringer Ingelheim, Chugai, Daiichi-Sankyo, Eisai, and Takeda. LG reports non-financial support from UCB Pharma, during the conduct of the study; grants from Amgen, Galapagos, Lilly, Pfizer, Sandoz, and UCB Pharma; personal fees from AbbVie, Amgen, BMS, Celltrion, Galapagos, Gilead, Janssen, Lilly, MSD, Novartis, Pfizer, Sandoz, and UCB Pharma; and non-financial support from AbbVie, Janssen, Novartis, Pfizer, and UCB Pharma, outside the submitted work. ABG reports honoraria as an advisory board member, non-promotional speaker, or consultant for Amgen, AnaptysBio, Avotres Therapeutics, BMS, Boehringer Ingelheim, Dermavant, Eli Lilly, Janssen, Novartis, Pfizer, Sanofi, Sun Pharma, UCB Pharma, and Xbiotech (stock options); and research or educational grants from AnaptysBio, BMS, Janssen, Novartis, Ortho Dermatologics, Sun Pharma, and UCB Pharma (all funds go to the Icahn School of Medicine at Mount Sinai). RBW reports 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; and honoraria from Astellas, DiCE, GSK, and Union. BI is an employee and stockholder of UCB Pharma and a stockholder of GSK and AbbVie. DA, RB, VS, and JC are all employees and stockholders of UCB Pharma. PJM reports research grants from AbbVie, Amgen, BMS, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, Sun Pharma, and UCB Pharma; consultancy fees from AbbVie, Acelyrin, Aclaris, Amgen, BMS, Boehringer Ingelheim, Eli Lilly, Galapagos, Gilead, GSK, Inmagene, Janssen, Moonlake Pharma, Novartis, Pfizer, Sun Pharma, and UCB Pharma; and speakers' bureau fees from AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer, and UCB Pharma., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Objective: To assess the long-term safety, tolerability, and efficacy of bimekizumab in active psoriatic arthritis (PsA)., Methods: Adult patients with active PsA who completed the double- and dose-blind periods of the BE ACTIVE randomized controlled trial were eligible to enroll in the open-label extension (OLE) study at week 48, after which patients received 160 mg of bimekizumab every 4 weeks. Safety and efficacy results are presented through 152 weeks., Results: At week 152, 161 of 206 patients (78.2%) remained in the study. From weeks 0-152, 184 of 206 patients experienced ≥1 treatment-emergent adverse event (126.4 per 100 patient-years). The most frequent events were nasopharyngitis (7.6 per 100 patient-years), upper respiratory tract infection (6.8 per 100 patient-years), bronchitis (3.5 per 100 patient-years), and oral candidiasis (3.5 per 100 patient-years). Additionally, 47 of 206 patients had mild to moderate localized fungal infections (9.7 per 100 patient-years), including 24 of 206 patients who had Candida infections (4.6 per 100 patient years) and 19 of 206 patients who had oral candidiasis (3.5 per 100 patient years). Four patients had serious infections (0.7 per 100 patient-years); there were no reported cases of active tuberculosis, adjudicated major adverse cardiac events, or deaths. Efficacy demonstrated at week 48 was sustained in the OLE study. At week 152, nonresponder imputation analysis showed that 52.9% of patients (69.4% of observed cases) achieved the American College of Rheumatology criteria for 50% improvement, 57.7% (73.8% of observed cases) achieved 100% skin clearance per the Psoriasis Area and Severity Index, and 51.5% (67.5% of observed cases) achieved minimal disease activity. Patients also maintained improvements in pain, physical function, and health-related quality of life., Conclusion: The safety profile of bimekizumab was consistent with previous reports, with no new safety signals identified. Sustained joint and efficacy responses were observed over 3 years., (© 2022 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Objectives: Bimekizumab selectively neutralises both interleukin (IL)-17A and IL-17F. We report efficacy and safety in a phase IIb dose-ranging study in patients with active ankylosing spondylitis (AS)., Methods: Adults with AS (fulfilling modified New York criteria) were randomised 1:1:1:1:1 to bimekizumab 16 mg, 64 mg, 160 mg, 320 mg or placebo every 4 weeks for 12 weeks (double-blind period). At week 12, patients receiving bimekizumab 16 mg, 64 mg or placebo were re-randomised 1:1 to bimekizumab 160 mg or 320 mg every 4 weeks to week 48; other patients continued on their initial dose (dose-blind period). The primary end point was Assessment of SpondyloArthritis international Society (ASAS) 40 response at week 12 (non-responder imputation (NRI) for missing data)., Results: 303 patients were randomised: bimekizumab 16 mg (n=61), 64 mg (n=61), 160 mg (n=60), 320 mg (n=61) or placebo (n=60). At week 12, significantly more bimekizumab-treated patients achieved ASAS40 vs placebo (NRI: 29.5%-46.7% vs 13.3%; p<0.05 all comparisons; OR vs placebo 2.6-5.5 (95% CI 1.0 to 12.9)). A significant dose-response was observed (p<0.001). The primary end point was supported by all secondary efficacy outcomes. At week 48, 58.6% and 62.3% of patients receiving bimekizumab 160 and 320 mg throughout the study achieved ASAS40, respectively (NRI); similar ASAS40 response rates were observed in re-randomised patients. During the double-blind period, treatment-emergent adverse events occurred in 26/60 (43.3%) patients receiving placebo and 92/243 (37.9%) receiving bimekizumab., Conclusions: Bimekizumab provided rapid and sustained improvements in key outcome measures in patients with active AS, with no unexpected safety findings versus previous studies., Trial Registration Number: NCT02963506., Competing Interests: Competing interests: DvdH reports personal fees from AbbVie, Amgen, Astellas, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Cyxone, Daiichi, Eisai, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda and UCB Pharma, and is Director of Imaging Rheumatology BV. LSG reports grants and personal fees from AbbVie, Amgen, Novartis, Pfizer and UCB Pharma, and personal fees from Galapagos, Janssen and Eli Lilly. AD reports personal fees from Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Galapagos and Janssen, and grants and personal fees from AbbVie, Eli Lilly, GlaxoSmithKline, Novartis, Pfizer and UCB. DP reports personal fees from UCB Pharma, BMS, Roche and Celgene, and grants and personal fees from AbbVie, Eli Lilly, MSD, Novartis and Pfizer. XB reports personal fees from AbbVie, Bristol-Myers Squibb, Celgene, Chugai, Janssen, MSD, Novartis, Pfizer and UCB Pharma, and grant/research support from Abbvie, MSD and Novartis. AK reports research support from Altoona Centernical Research, PC, during the conduct of the study; Advisory Committee or Review Panel for AbbVie, Janssen, UCB Pharma and Boehringer Ingelheim; speaking and teaching for Celgene, Horizon, Merck and Novartis; Advisory Committee or Review Panel, speaking and training for Genzyme; Advisory Committee or Review Panel, speaking/training; consultant, and stocks for Pfizer and Sanofi; Advisory Committee or Review Panel, speaking/training and consultant for Regeneron; consultant for SUN Pharma Advanced Research; Speaker and Steering Committee for Flexion; Stocks from Amgen, Gilead and GSK and Speaker for AbbVie. MO, DB and NG are employees of UCB Pharma and own stocks and stock options. JC is an employee of UCB Pharma. MKF was an employee of UCB Pharma at the time the study was conducted (current employee of Kezar Life Sciences). MD reports grants and personal fees from UCB, Eli Lilly, Novartis, Pfizer, AbbVie and Merck., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Dual neutralisation of interleukin 17A (IL17A) and interleukin 17F (IL17F) is a potential novel therapeutic approach in psoriatic arthritis. We assessed bimekizumab, a monoclonal antibody that selectively neutralises IL17A and IL17F, in patients with active psoriatic arthritis., Methods: BE ACTIVE was a randomised, double-blind, placebo-controlled, dose-ranging phase 2b study done at 41 sites in the Czech Republic, Germany, Hungary, Poland, Russia, and the USA. Eligible patients aged 18 years or older with active adult-onset psoriatic arthritis and symptoms for at least 6 months were randomly assigned (1:1:1:1:1) to placebo, 16 mg bimekizumab, 160 mg bimekizumab, 160 mg bimekizumab with a one-off 320 mg loading dose, or 320 mg bimekizumab, which were administered as subcutaneous injections every 4 weeks for 12 weeks. After 12 weeks, patients assigned to the placebo and 16 mg bimekizumab groups were randomly reassigned (1:1) to either 160 mg or 320 mg bimekizumab, and all other patients remained on their originally assigned initial dose up to 48 weeks. Both participants and researchers were blinded to treatment allocation in the first 12 weeks, and blinded to the dose of bimekizumab thereafter. The primary endpoint was the proportion of patients with at least 50% improvement in the American College of Rheumatology response criteria at week 12, which was assessed in all patients who received at least one dose of study treatment and had a valid measurement of the primary efficacy endpoint at baseline. The trial, including all follow-up, has been completed. This trial is registered with ClinicalTrials.gov, NCT02969525., Findings: Between Oct 27, 2016, and July 16, 2018, 308 patients were screened, and 206 were randomly assigned: 42 to the placebo group, and 41 each to the four bimekizumab groups. At 12 weeks, compared with the placebo group, significantly more patients in the 16 mg bimekizumab (odds ratio [OR] 4·2 [95% CI 1·1-15·2]; p=0·032), 160 mg bimekizumab (8·1 [2·3-28·7]; p=0·0012), and 160 mg (loading dose) bimekizumab (9·7 [2·7-34·3]; p=0·0004) groups achieved an ACR50 response. At 12 weeks, 24 (57%) of 42 patients in the placebo group and 68 (41%) of the 164 patients in the bimekizumab groups reported treatment-emergent adverse events. Most of these adverse events were mild or moderate. Serious treatment-emergent adverse events occurred in nine patients, eight of whom were receiving bimekizumab. No deaths or cases of inflammatory bowel disease were reported., Interpretation: Bimekizumab doses of 16 mg and 160 mg (with or without a 320 mg loading dose) were associated with significant improvements in ACR50 compared with placebo, with an acceptable safety profile. Our results support phase 3 investigation of bimekizumab as a treatment for psoriatic arthritis., Funding: UCB Pharma., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Certolizumab pegol is an effective biologic for patients with Crohn's disease (CD). Individual differences in certolizumab pegol apparent clearance (CL/F) affect exposure and possibly efficacy. A previously developed population pharmacokinetic (PK) model did not account for dynamic changes in clinical parameters during therapy., Objective: The aim of this study was to refine the existing PK model to capture the time-varying influence of covariates., Methods: Data collected from 2157 Crohn's disease patients in nine studies were analyzed using nonlinear mixed-effects modeling software (NONMEM). Certolizumab pegol concentration-time data were described by a one-compartment PK model with first-order absorption, and one-compartment disposition with linear, time-dependent elimination using antidrug antibody (ADAb) concentration as a continuous variable., Results: The final dataset consisted of 12,926 analyzable records. Parameter estimates were absorption rate constant 1.83/day, CL/F 0.527 L/day, and apparent volume of distribution (V/F) 8.33 L. ADAb concentration (2.5-214 units/mL) increased the median CL/F by 142-174%. For a typical patient, body weight (46.8-100.5 kg) increased the median CL/F and V/F from 82 to 120%. Albumin (32-48 g/L) decreased and C-reactive protein (0.5-54.0 mg/L) increased the median CL/F from 123 to 85% and from 83 to 113%, respectively. Between-patient variability of CL/F was 19.6%., Conclusions: By incorporating time-varying covariates, this population PK model reduces between-patient variability on CL/F estimates, and the relative influence of ADAb can now be assessed. As Crohn's disease patient covariates are often time-dependent, this model is more reflective of patient drug exposure with sustained treatment.

Background: Anti-drug antibodies (ADAbs) may decrease the efficacy of biologics and increase the risk of adverse events. A single positive test may not preclude further treatment because of variations in assays used, test timing, and patient variables. We evaluated the longitudinal patterns of immunogenicity during 7 years of antitumor necrosis factor-alpha drug certolizumab pegol (CZP) treatment for moderate-to-severe Crohn's disease., Methods: PRECiSE 3 patients (n = 595) received open-label CZP 400 mg every 4 weeks up to 7 years. CZP-ADAb expression, plasma CZP concentration, Harvey-Bradshaw Index, C-reactive protein, and fecal calprotectin concentrations were measured multiple times. Longitudinal data, examined for CZP-ADAb positivity and categorized as transient (with temporary/no effect on CZP concentration), persistent, or negative, were correlated with clinical and biological variables., Results: Of the CZP-ADAb-positive patients, 40 (22.6%) had transient CZP-ADAbs and 94 (77.4%) had persistent CZP-ADAbs. Demographic characteristics were similar between groups. Median C-reactive protein and fecal calprotectin were higher (P < 0.05 at some visits) and plasma CZP concentrations were significantly lower (P < 0.0001 at all visits) in the persistent CZP-ADAb-positive group relative to the CZP-ADAb-negative group. Transient CZP-ADAb-positive and CZP-ADAb-negative patients had similar plasma CZP, C-reactive protein, and fecal calprotectin concentrations. Median Harvey-Bradshaw Index scores and rates of adverse events were similar among groups., Conclusions: This analysis demonstrates that persistent CZP-ADAb has negative effects on drug levels and efficacy, whereas transient expression may not. Serial measurements may be needed to characterize ADAb positivity. www.clinicaltrials.gov, Number NCT00160524.

Background & Aims: Treatments for Crohn's disease (CD) have been linked to serious infections, malignancies, and dermatologic complications. We pooled and analyzed clinical trials of certolizumab pegol, a pegylated humanized Fab' fragment against tumor necrosis factor, to quantify safety events in patients with CD., Methods: We collected data from 5 placebo-controlled trials, 9 open-label studies, and 1 dose-regimen study, conducted globally through April 2014. A total of 2570 patients with moderate to severe CD were treated with certolizumab pegol, with 4378.1 patient-years of exposure. Data were analyzed in 2 groups: patients from placebo-controlled (PC) trials treated with placebo (n = 875) or certolizumab pegol (n = 919) for 6 to 38 weeks (the PC group) or all patients exposed to certolizumab pegol (n = 2570), for durations of 6 to 362 weeks (the all-studies group). Incidence rates (IRs; incidence/100 patient-years) of adverse events (AEs) were calculated from first dose through 70 days (approximately 5 half-lives) after the last dose., Results: In the PC group, IRs for serious AEs were similar among patients given certolizumab pegol (31.35/100 patient-years) vs placebo (24.33/100 patient-years). IRs of serious infections or malignancies were low among patients receiving short-term treatment with certolizumab pegol (8.49/100 patient-years and 1.01/100 patient-years, respectively, in the PC group) and did not increase with long-term treatment (6.47/100 patient-years and 0.80/100 patient-years, respectively, in the all-studies group). IRs of psoriasis or psoriasiform dermatitis were low in the PC group (1.01/100 patient-years and 0/100 patient-years, respectively); in the placebo group, these IRs were 0.38 per 100 patient-years and 0 per 100 patient-years, respectively. IRs of psoriasis or psoriasiform dermatitis did not increase with long-term treatment (0.93/100 patient-years and 0.09/100 patient-years, respectively, in the all-studies group)., Conclusions: Based on an analysis of data pooled from 15 trials of patients with CD, the safety profile for long-term therapy with certolizumab pegol therapy is similar to that reported from short-term studies. Overall rates of AEs, serious infections, malignancies, and psoriasis did not increase with long-term treatment, suggesting a favorable risk-benefit ratio with long-term certolizumab pegol therapy in CD. Clinicaltrials.gov identifiers: NCT00291668, NCT00152490, NCT00152425, NCT00308581, NCT00349752, NCT00552058, NCT00329550, NCT00329420, NCT00160524, NCT00160706, NCT00297648, NCT00333788, NCT00307931, NCT00356408, and NCT00552344 (https://www.clinicaltrials.gov/ct2/search)., (Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: In Crohn's disease (CD), rapid response to anti-tumor necrosis factor therapy improves short- and medium-term outcomes, but the relationship between early remission (ER) and long-term remission is unclear., Aims: This exploratory analysis of PRECiSE 3 (NCT00160524) assessed whether ER after initiation of certolizumab pegol predicted long-term remission., Methods: Patients enrolled in PRECiSE 3 had completed PRECiSE 1 or 2, two randomized placebo-controlled studies for moderate to severe CD, and received open-label certolizumab pegol 400 mg every 4 weeks for a total treatment duration of ≤7.5 years. Time to loss of remission between patients with and without ER (Harvey-Bradshaw Index ≤4 at or before Week 6 of PRECiSE 1 or 2) was compared by log-rank test of Kaplan-Meier estimates., Results: At baseline, patients with (n = 242) and without (n = 148) ER had mean (standard deviation [SD]) durations of CD of 6.8 (6.6) and 7.4 (7.8) years, mean (SD) CD Activity Index scores of 280.3 (53.4) and 311.1 (55.5), with 45.5% and 41.9% of patients having ileocolonic CD, and median C-reactive protein concentrations of 8.0 and 5.0 mg/L, respectively. Median certolizumab pegol plasma concentrations during the first 6 weeks of therapy were similar in both groups. Mean time to loss of remission was significantly longer in patients with versus without ER (2.77 vs. 1.14 years, p < 0.0001)., Conclusions: In certolizumab pegol-treated patients with CD, ER appears to be an important predictor of long-term clinical remission. Prospective trials are needed to determine whether ER improves other long-term outcomes.

Background: Patients with Crohn's disease in whom tumor necrosis factor antagonist therapy fails have limited treatment options, and the benefit of reintroducing the same therapy remains unclear. Here, we report results from PRECiSE 4 (NCT00160706), an open-label extension study of certolizumab pegol in patients who withdrew from the placebo-controlled studies PRECiSE 1 or 2., Methods: Patients eligible for PRECiSE 4 had Crohn's disease exacerbation on placebo or primary or secondary failure to certolizumab pegol in PRECiSE 1 or 2, and received 400 mg certolizumab pegol subcutaneously at weeks 0, 2, and 4 and every 4 weeks thereafter up to 360 weeks. We assessed safety (adverse events) and efficacy (clinical remission) of extended certolizumab pegol therapy., Results: Patients enrolled in PRECiSE 4 (N = 310; mean age, 37 yr; 58% female; 95% white) had a mean Crohn's disease duration of 8.5 years before entering the qualifying studies. At weeks 52, 104, and 156, remission rates were 28.5%, 17.5%, and 12.6% by nonremitter imputation, and 63.8%, 60.0%, and 63.5% by observed cases, with 47.4%, 31.9%, and 23.2% of patients, respectively, remaining on therapy. By study end (7.5 yr), 92.3% of patients discontinued therapy, 49% on account of adverse events. No new safety signals emerged. Incidence rate (new cases)/100 patient-years was 6.11 for serious infections and 1.29 for malignancies., Conclusions: Certolizumab pegol was effective in many patients who previously discontinued certolizumab pegol for lack or loss of response. Thus, discontinuation of therapy may not always be necessary. Safety was consistent with previous findings.

The spontaneous reporting of adverse drug reactions (ADRs) at the St. John's Hospital and Memorial Medical Center was well below that reported in the literature. After review of procedures for reporting of ADRs at these institutions, the authors developed a system that was approved by their joint P & T Committee. The ADR reporting program developed uses concurrent monitoring of most hospital inpatients and a retrospective review of all emergency room patients. In the year after program implementation, 162 ADR reports were documented. From this program, a group of serious ADRs to one agent was identified and reported, both to the Food and Drug Administration and to the manufacturer. A well-developed ADR monitoring program may lead to heightened physician and nurse awareness and early problem identification, possibly decreasing morbidity for hospitalized patients.

The development and use of price and value indexes that differentiate between the effects of price and volume changes on a hospital's cost of drug products and related supplies are discussed. To construct a price index it is necessary to (1) compile a general list of drug products representative of a major portion of the institution's annual drug expenditure, (2) assign appropriate weights (quantity determinants) to these listed products, (3) select a base period that reflects normal hospital operations, and (4) select a suitable equation, the authors' choice being a fixed-weight aggregates method. The value index, which measures the combined effects of acquisition cost changes and volume changes, can be calculated when the acquisition cost change for the period is known. Information derived from the indexes can be used in (1) cost analysis and operational forecasts, (2) measurement and assessment of purchasing and inventory control, and (3) simplification of procurement and inventory processes.