Long-Term Safety and Efficacy of the Anti-Mucosal Addressin Cell Adhesion Molecule-1 Monoclonal Antibody Ontamalimab (SHP647) for the Treatment of Crohn’s Disease: The OPERA II Study
| العنوان: | Long-Term Safety and Efficacy of the Anti-Mucosal Addressin Cell Adhesion Molecule-1 Monoclonal Antibody Ontamalimab (SHP647) for the Treatment of Crohn’s Disease: The OPERA II Study |
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| المؤلفون: | Anindita Banerjee, Edouard Louis, Satyaprakash Nayak, Jochen Klaus, Kenneth J. Gorelick, Stefan Schreiber, Steven W. Martin, William J. Sandborn, Maria Kłopocka, Geert R. D'Haens, Xavier Hébuterne, Scott D. Lee, Fabio Cataldi, Peter Nagy, Walter Reinisch, Dino Tarabar, Dong Il Park |
| المساهمون: | Gastroenterology and Hepatology, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism |
| المصدر: | Inflammatory bowel diseases, 28(7), 1034-1044. John Wiley and Sons Inc. |
| بيانات النشر: | Oxford University Press (OUP), 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | medicine.medical_specialty, Antibodies, Monoclonal, Humanized, Placebo, Gastroenterology, Crohn Disease, Pharmacokinetics, Internal medicine, medicine, Addressin, Humans, Immunology and Allergy, ontamalimab, Adverse effect, Crohn's disease, biology, business.industry, Cell Adhesion Molecule-1, Antibodies, Monoclonal, clinical trial, medicine.disease, Discontinuation, Treatment Outcome, Tolerability, biology.protein, mucosal addressin cell adhesion molecule-1, Biomarker (medicine), business |
| الوصف: | Background Patients with Crohn’s disease (CD) experience intestinal inflammation. Ontamalimab (SHP647), a fully human immunoglobulin G2 monoclonal antibody against mucosal addressin cell adhesion molecule-1, is a potential novel CD treatment. OPERA II, a multicenter, open-label, phase 2 extension study, assessed the long-term safety and efficacy of ontamalimab in patients with moderate-to-severe CD. Methods Patients had completed 12 weeks of blinded treatment (placebo or ontamalimab at 22.5, 75, or 225 mg subcutaneously) in OPERA (NCT01276509) or had a clinical response to ontamalimab 225 mg in TOSCA (NCT01387594). Participants received ontamalimab at 75 mg every 4 weeks (weeks 0–72), then were followed up every 4 weeks for 24 weeks. One-time dose reduction to 22.5 mg or escalation to 225 mg was permitted at the investigator’s discretion. The primary end points were safety and tolerability outcomes. Secondary end points included changes in serum drug and biomarker concentrations. Efficacy end points were exploratory, and used non-responder imputation methods. Results Overall, 149/268 patients completed the study. The most common adverse event leading to study discontinuation was CD flare (19.8%). Two patients died; neither death was considered to be drug related. No dose reductions occurred; 157 patients had their dose escalated. Inflammatory biomarker concentrations decreased. Serum ontamalimab levels were consistent with known pharmacokinetics. Remission rates (Harvey-Bradshaw Index [HBI] ≤ 5; baseline, 48.1%; week 72, 37.3%) and response rates (baseline [decrease in Crohn’s Disease Activity Index ≥ 70 points], 63.1%; week 72 [decrease in HBI ≥ 3], 42.5%) decreased gradually. Conclusions Ontamalimab was well tolerated; treatment responses appeared to be sustained over 72 weeks. ClinicalTrials.gov ID: NCT01298492. |
| تدمد: | 1536-4844 1078-0998 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::42c598bd58d2a3ecd2978a58a504cb71 https://doi.org/10.1093/ibd/izab215 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....42c598bd58d2a3ecd2978a58a504cb71 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15364844 10780998 |
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