Silvio Danese, MD, PhD; Gionata Fiorino, MD, PhD; Laurent Peyrin-Biroulet, MD, PhD; Ersilia Lucenteforte, ScD, PhD; Gianni Virgili, MD; Lorenzo Moja, MD, MSc, DrPH; Stefanos Bonovas, MD, MSc, PhD
Grant Support: By the Centro Ricerca e Cura delle Malattie Infiammatorie Croniche Intestinali, IRCCS Istituto Clinico Humanitas.
Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M13-2403.
Requests for Single Reprints: Silvio Danese, MD, PhD, Inflammatory Bowel Disease Center, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano, Milan, Italy; e-mail, firstname.lastname@example.org.
Current Author Addresses: Drs. Danese and Fiorino: Inflammatory Bowel Disease Center, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano, Milan, Italy.
Dr. Peyrin-Biroulet: Inserm U954 and Department of Hepato-Gastroenterology, University Hospital of Nancy, Université de Lorraine, Vandoeuvre-lès-Nancy, France.
Dr. Lucenteforte: Department of Neurosciences, Psychology, Drug Research and Child Health, University of Florence, Viale Pieraccini 6, 50139 Florence, Italy.
Dr. Virgili: Department of Specialised Surgical Sciences, University of Florence, Via le Morgagni 85, 50134 Florence, Italy.
Dr. Moja: Clinical Epidemiology Unit, IRCCS Orthopedic Institute Galeazzi, Via R. Galeazzi 4, 20161 Milan, Italy.
Dr. Bonovas: Department of Pharmacology, School of Medicine, University of Athens, 75 Mikras Asias Street, 11527 Athens, Greece.
Author Contributions: Conception and design: S. Danese, G. Fiorino, L. Peyrin-Biroulet, L. Moja, S. Bonovas.
Analysis and interpretation of the data: S. Danese, E. Lucenteforte, G. Virgili, L. Moja, S. Bonovas.
Drafting of the article: S. Danese, L. Peyrin-Biroulet, L. Moja, S. Bonovas.
Critical revision of the article for important intellectual content: S. Danese, G. Fiorino, L. Peyrin-Biroulet, E. Lucenteforte, G. Virgili, L. Moja, S. Bonovas.
Final approval of the article: S. Danese, G. Fiorino, L. Peyrin-Biroulet, E. Lucenteforte, G. Virgili, L. Moja, S. Bonovas.
Provision of study materials or patients: G. Fiorino.
Statistical expertise: E. Lucenteforte, G. Virgili, S. Bonovas.
Administrative, technical, or logistic support: S. Danese.
Collection and assembly of data: S. Danese, G. Fiorino, S. Bonovas.
Biological agents are emerging treatment options for the management of ulcerative colitis (UC).
To assess the comparative efficacy and harm of biological agents in adult patients with moderately to severely active UC who are naive to biological agents.
MEDLINE, EMBASE, and Cochrane Library from inception through December 2013, without language restrictions, and ClinicalTrials.gov, European Medicines Agency, and U.S. Food and Drug Administration Web sites.
Randomized, placebo-controlled or head-to-head trials assessing biological agents as induction or maintenance therapy for moderately to severely active UC.
Two reviewers independently abstracted study data and outcomes and rated each trial's risk of bias.
There were no head-to-head trials. There were 7 double-blind, placebo-controlled trials that were rated as low risk of bias and showed that all biological agents (adalimumab, golimumab, infliximab, and vedolizumab) resulted in more clinical responses, clinical remissions, and mucosal healings than placebo for induction therapy. The results of network meta-analysis suggested that infliximab is more effective to induce clinical response (odds ratio, 2.36 [95% credible interval, 1.22 to 4.63]) and mucosal healing (odds ratio, 2.02 [95% credible interval, 1.13 to 3.59]) than adalimumab. No other indirect comparison reached statistical significance. For maintenance, 6 double-blind, placebo-controlled trials that were rated high risk of bias showed that all biological agents have greater clinical efficacy than placebo. The occurrence of adverse events was not different between biological agents and placebo.
Few trials, no head-to-head comparisons, and inadequate follow-up in maintenance trials.
Biological agents are effective treatments for UC, but head-to-head trials are warranted to establish the best therapeutic option.
Centro Ricerca e Cura delle Malattie Infiammatorie Croniche Intestinali, IRCCS Istituto Clinico Humanitas. (PROSPERO registration number: CRD42013005459)
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Danese S, Fiorino G, Peyrin-Biroulet L, Lucenteforte E, Virgili G, Moja L, et al. Biological Agents for Moderately to Severely Active Ulcerative Colitis: A Systematic Review and Network Meta-analysis. Ann Intern Med. 2014;160:704–711. doi: 10.7326/M13-2403
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Published: Ann Intern Med. 2014;160(10):704-711.
Gastroenterology/Hepatology, Inflammatory Bowel Disease.
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