Abstract Background Tulisokibart, a humanized tumor necrosis factor-like cytokine 1A (TL1A) monoclonal antibody, maintained clinical remission and endoscopic response through 50 weeks in participants with moderately to severely active ulcerative colititis (UC) in the phase 2, double-blind, placebo-controlled ARTEMIS-UC study (NCT04996797). We assessed symptomatic relief through changes in stool frequency (SF) and rectal bleeding (RB) subscores, as well as disease clearance, defined as the combination of symptomatic relief and mucosal healing, through 50 weeks. Methods In ARTEMIS-UC, participants were randomized to receive intravenous (IV) tulisokibart 1000 mg on day 1 and 500 mg at weeks 2, 6, and 10 or placebo. Responders (reduction of ≥ 2 points and ≥30% in modified Mayo score from baseline, and a reduction ≥1 in RB subscore or absolute RB subscore ≤1 at week 12) were randomized to receive open-label IV tulisokibart 100 mg or 250 mg every 4 weeks through week 170. SF normalisation (score of 0 or 1 and no greater than baseline), resolution of RB (score of 0), symptomatic remission (achievement of both SF normalisation and RB resolution), and disease clearance (symptomatic remission and mucosal healing Geboes score ≤2B.1 and endoscopy subscore ≤1) are reported via descriptive statistics in the full analysis set through week 12 and in induction responders through week 50. Participants with missing data were imputed as nonresponders. Results At week 12, a higher proportion of participants treated with tulisokibart compared with placebo achieved SF normalisation (57.4% vs 17.9%, respectively), RB resolution (61.8% vs 34.3%), and symptomatic remission (47.1% vs 13.4%), with improvements observed as early as week 2 (Figure 1). Among week 12 responders randomised to tulisokibart 100 mg or 250 mg, efficacy was sustained or continued to increase through week 50 in SF normalisation (63.6% and 76.0%, respectively), RB resolution (63.6% and 72.0%), and symptomatic remission (54.5% and 68.0%). The proportion of participants who achieved disease clearance was also greater with tulisokibart (25.0%) vs placebo (1.5%) at week 12 and continued to increase among week 12 responders through week 50 in the tulisokibart 100-mg group (31.8%) and 250-mg group (44.0%) (Figure 2). Conclusion Participants treated with tulisokibart achieved higher rates of SF normalisation, resolution of RB, symptomatic remission, and disease clearance compared with placebo at week 12. Among week 12 responders treated with tulisokibart 250 mg, symptomatic remission and disease clearance were achieved in 68% and 44% of participants, respectively, by 1 year. A phase 3 trial to confirm these findings is ongoing. Conflict of interest: Ma, Christopher: Consulting fees: AbbVie, Alimentiv, Amgen, Anaptys Bio, AVIR Pharma Inc, Bristol Myers Squibb, Celltrion, Domain Therapeutics, Eupraxia, Eli Lilly, Ferring, Forte Biosciences, Fresenius Kabi, Gilead, Janssen, McKesson, Merck, Mirador Therapeutics, Pendopharm, Pfizer, Roche, Sanofi, Takeda, Tillotts Pharma Speaker’s fees: AbbVie, Amgen, AVIR Pharma Inc, Alimentiv, Bristol Myers Squibb, Eli Lilly, Ferring, Fresenius Kabi, Janssen, Merck, Organon, Pendopharm, Pfizer, Sanofi, Takeda, Tillotts Pharma Royalties: Springer Publishing Research Support: AbbVie, Eli Lilly, Ferring, Pfizer Boland, Brigid: Consultant: AbbVie, Celltrion, Merck, and Sanofi. Research support: Merck, Prometheus Biosciences, Mirador, Gilead, and SRT Therapeutics Leszczyszyn, Jaroslaw: Vasa Therapeutics LLC Xu, Zhi Jin: Employees: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. Shao, Jeremy: Employees: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. Feagan, Brian Gordon: Consulting Fees: AbbVie, Abivax, Adaxion, Adiso, AgomAB Therapeutics, Akros, Alira Health, Ally Bridge Group, Apini Therapeutics, Argenx, Attovia Tx, Avoro Capital Advisors, Belmore Law, Biora Therapeutics, Blackbird Laboratories, Boehringer-Ingelheim, BMS, Boxer Capital, Celgene/BMS, Clarivate, Connect Biopharm, EcoR1, Eli Lilly, Ensho Therapeutics, Equillium, Evida, Enveda, Evommune Inc. Faes Farma, First Wave, Forbion, Galapagos, Genentech/Roche, General Atlantic, Genesis Therapeutics, Gerson Lehrman Group, Gilead, Guidepoint, Imhotex, ImiDomics, Immunic Therapeutics, Janssen, Japan Tobacco Inc., LifeMine Therapeutics, Mage Biologics, Merck, Mirador Therapeutics, Mobius Care, Monte Rosa Tx, Morphic Therapeutics, Nimbus Therapeutics, Novartis, Nxera, OncoC3, Palisade Bio, Pendopharm, Pfizer,Q32 Bio, REDX, Roche, Sanofi, Sobi, Sorriso, Spyre Therapeutics, Sun Pharma, Surrozen Inc., Synedgen, Takeda, Tegus Inc., Teva, Tillotts, Trex Bio, TR1X Inc. TVM Lifesciences, Ventyx Biosciences, Versant Ventures, Vida Ventures, Ysios Capital, Zagbio Stock Shareholder: Connect Biopharm, EnGene, Evida, SRT, Imidomics, Enveda
Ma et al. (Thu,) studied this question.