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
| العنوان: | 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 |
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| المؤلفون: | Tomáš Vaňásek, Miles P. Sparrow, Maria Kłopocka, Paul Hellstern, Kenneth J. Gorelick, Martina Goetsch, Xavier Hébuterne, Fabio Cataldi, Caleb Bliss, Dino Tarabar, Charu Gupta, William J. Sandborn, Miloš Greguš, Michael Hoy, Severine Vermeire, Silvio Danese, Joo Sung Kim, Walter Reinisch |
| المصدر: | Journal of Crohn's & Colitis |
| بيانات النشر: | Oxford University Press (OUP), 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Adult, Male, medicine.medical_specialty, medicine.drug_class, Dose-Response Relationship, Immunologic, Lymphoproliferative disorders, Antibodies, Monoclonal, Humanized, Placebo, Monoclonal antibody, Gastroenterology, Endoscopy, Gastrointestinal, Eccojc/1040, Mucoproteins, Gastrointestinal Agents, Internal medicine, medicine, Humans, MAdCAM-1, Adverse effect, AcademicSubjects/MED00260, business.industry, Progressive multifocal leukoencephalopathy, Original Articles, General Medicine, medicine.disease, Faecal calprotectin, Ulcerative colitis, C-Reactive Protein, Treatment Outcome, Tolerability, phase 2, Colitis, Ulcerative, Female, Drug Monitoring, business, Cell Adhesion Molecules, Leukocyte L1 Antigen Complex |
| الوصف: | Background and Aims 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. Methods 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. Results 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]. Conclusions Ontamalimab was well tolerated up to 144 weeks in patients with moderate-to-severe UC, with good safety and efficacy. |
| وصف الملف: | |
| تدمد: | 1876-4479 1873-9946 0177-1809 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::bba1d3a76d8538b8cc21296a42160dd7 https://doi.org/10.1093/ecco-jcc/jjab023 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....bba1d3a76d8538b8cc21296a42160dd7 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 18764479 18739946 01771809 |
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