Secukinumab, a human anti-IL-17A monoclonal antibody, for moderate to severe Crohn's disease: unexpected results of a randomised, double-blind placebo-controlled trial
| Autor: | Steve Lewitzky, Wolfgang Hueber, Marc Vandemeulebroecke, Gervais Tougas, Bjoern Mellgard, Arthur P. Bertolino, Jacek Karczewski, Stephan Bek, Jan Wehkamp, Nicole Pezous, Brian G. Feagan, Gerard Bruin, Marco Londei, Simon Travis, Michael D Yao, Bruce E. Sands, Walter Reinisch, Peter D.R. Higgins, Claudia Berger, Marek Karczewski |
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| Rok vydání: | 2012 |
| Předmět: |
Adult
Genetic Markers Male medicine.medical_specialty Adolescent Anti-Inflammatory Agents Placebo-controlled study Antibodies Monoclonal Humanized Placebo Polymorphism Single Nucleotide Severity of Illness Index Gastroenterology Drug Administration Schedule Young Adult Crohn Disease Double-Blind Method Internal medicine medicine Clinical endpoint Humans Treatment Failure Infusions Intravenous Aged business.industry Interleukin-17 Therapeutic effect Area under the curve Antibodies Monoclonal Bayes Theorem Middle Aged Faecal calprotectin Surgery Female Secukinumab Calprotectin business Leukocyte L1 Antigen Complex Biomarkers |
| Zdroj: | Gut. 61:1693-1700 |
| ISSN: | 1468-3288 0017-5749 0100-9281 |
| Popis: | OBJECTIVE: The authors tested whether the anti-interleukin (IL)-17A monoclonal antibody secukinumab was safe and effective for the treatment of active Crohn's disease. DESIGN: In a double-blind, randomised, placebo-controlled proof-of-concept study, 59 patients with moderate to severe Crohn's disease (Crohn's Disease Activity Index (CDAI) ≥220 to ≤450) were assigned in a 2:1 ratio to 2×10 mg/kg intravenous secukinumab or placebo. The primary end point, addressed by bayesian statistics augmented with historical placebo information, was the probability that secukinumab reduces the CDAI by ≥50 points more than placebo at week 6. Ancillary analyses explored associations of 35 candidate genetic polymorphisms and faecal calprotectin response. RESULTS: 59 patients (39 secukinumab, 20 placebo, mean baseline CDAI 307 and 301, respectively) were recruited. 18/59 (31%) patients discontinued prematurely (12/39 (31%) secukinumab, 6/20 (30%) placebo), 10/59 (17%) due to insufficient therapeutic effect (8/39 (21%) secukinumab, 2/20 (10%) placebo). Fourteen serious adverse events occurred in 10 patients (seven secukinumab, three placebo); 20 infections, including four local fungal infections, were seen on secukinumab versus none on placebo. Primary end point analysis estimated |
| Databáze: | OpenAIRE |
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