Long-term Safety and Efficacy of the Anti-MAdCAM-1 Monoclonal Antibody Ontamalimab [SHP647] for the Treatment of Ulcerative Colitis: The Open-label Study TURANDOT II
Open Access
- 18 February 2021
- journal article
- research article
- Published by Oxford University Press (OUP) in Journal of Crohn's and Colitis
- Vol. 15 (6), 938-949
- https://doi.org/10.1093/ecco-jcc/jjab023
Abstract
Ontamalimab, a fully-human monoclonal antibody targeting MAdCAM-1, induced remission in patients with moderate-to-severe ulcerative colitis [UC] in the TURANDOT study. We aimed to assess long-term safety, tolerability, and efficacy of ontamalimab in TURANDOT II. TURANDOT II was a phase 2, multicentre, open-label [OL] study in patients with moderate-to-severe UC who completed TURANDOT on placebo or ontamalimab (NCT01771809). Patients were randomised to 75 mg or 225 mg ontamalimab every 4 weeks for 72 weeks [OL1]. The dosage could be increased to 225 mg from Week 8 at the investigator’s discretion. All patients then received 75 mg every 4 weeks for 72 weeks [OL2], followed by 6-month safety follow-up. The primary objective was safety, measured by adverse events [AEs], serious AEs [SAEs], and AEs leading to withdrawal. Mucosal healing [MH; centrally read endoscopy] was assessed. Of 330 patients, 180 completed OL1; 94 escalated to 225 mg; 127 completed OL2. Overall, 36.1% experienced drug-related AEs. The most common SAE [10.0%] was worsening/ongoing UC; 5.5% of patients had serious infections, the most common being gastroenteritis [0.9%]. One death and four cancers [all unrelated to ontamalimab] occurred. No PML [progressive multifocal leukoencephalopathy]/lymphoproliferative disorders occurred. Geometric mean high-sensitivity C-reactive protein [hsCRP] and faecal calprotectin decreased across OL1 in both dose groups. The proportion of patients assigned to placebo in TURANDOT achieving MH increased from 8.8% [6/68] at baseline to 35.3% at Week 16 [24/68; non-responder imputation]. The corresponding increase in the ontamalimab group was from 23.3% [61/262] to 26.7% [70/262]. Ontamalimab was well tolerated up to 144 weeks in patients with moderate-to-severe UC, with good safety and efficacy.Keywords
Funding Information
- Takeda group of companies (NCT01771809)
- Pfizer
This publication has 32 references indexed in Scilit:
- Systematic review with network meta‐analysis: the impact of medical interventions for moderate‐to‐severe ulcerative colitis on health‐related quality of lifeAlimentary Pharmacology & Therapeutics, 2018
- Anti-MAdCAM antibody (PF-00547659) for ulcerative colitis (TURANDOT): a phase 2, randomised, double-blind, placebo-controlled trialThe Lancet, 2017
- Reassessing the risk of natalizumab-associated PMLJournal of NeuroVirology, 2016
- Correlation Between Concentrations of Fecal Calprotectin and Outcomes of Patients With Ulcerative Colitis in a Phase 2 TrialGastroenterology, 2016
- Optimizing anti-TNF treatments in inflammatory bowel diseaseAutoimmunity Reviews, 2014
- Fast and sharp decrease in calprotectin predicts remission by infliximab in anti-TNF naïve patients with ulcerative colitisJournal of Crohn's and Colitis, 2012
- The mucosal addressin cell adhesion molecule antibody PF-00547,659 in ulcerative colitis: a randomised studyGut, 2011
- Pharmacological characterization of PF‐00547659, an anti‐human MAdCAM monoclonal antibodyBritish Journal of Pharmacology, 2009
- C-reactive protein: a predictive factor and marker of inflammation in inflammatory bowel disease. Results from a prospective population-based studyGut, 2008
- A tissue-specific endothelial cell molecule involved in lymphocyte homingNature, 1988