Safety Profile of Biologic Drugs in the Treatment of Inflammatory Bowel Diseases: A Systematic Review and Network Meta-analysis of Randomized Controlled Trials.
OBJECTIVE
Biologic drugs are used in innovative therapies for the management of inflammatory bowel diseases (IBDs). The aim of this study was to compare the safety profile of biologic drugs in patients with IBD.


METHODS
A systematic literature search was performed using PubMed, Embase, and CENTRAL databases, up to 22 August 2016. We included randomized, placebo-controlled, or head-to-head clinical trials that compared the safety of different biologics in patients with IBDs. Two reviewers independently conducted the search and selection of studies and rated each trial's risk of bias. The network meta-analysis (NMA) was conducted for a mid-term (20-30 weeks) and long-term (≥52 weeks) follow-up with a Bayesian hierarchical random effects model using the ADDIS®software. The PROSPERO registration number was CRD42015029884.


RESULTS
Sixteen randomized controlled trials were included in the systematic review with NMA. In the case of the mid-term follow-up, it was possible to conduct the NMA for assessing the relative safety profile of certolizumab pegol and infliximab, and in the case of the long-term follow-up, of infliximab, adalimumab, golimumab, and vedolizumab. There were no significant differences in the rate of adverse events in patients treated with all analyzed biologic drugs for IBD. The analysis of probability for being the safest treatment showed that infliximab was the best option in most analyzed endpoints both in mid-term and in long-term follow-ups.


CONCLUSIONS
We showed no significant differences in the relative safety profile of the analyzed biologic drugs. Further studies are needed to confirm our findings, including head-to-head comparisons between these drugs.
Drug Management Department, Faculty of Health Sciences, Institute of Public Health, Jagiellonian University, ul. Grzegórzecka 20, 31-531, Kraków, Poland.
Paweł
P
Moćko
Drug Management Department, Faculty of Health Sciences, Institute of Public Health, Jagiellonian University, ul. Grzegórzecka 20, 31-531, Kraków, Poland. pawel.kawalec@uj.edu.pl.
Paweł
P
Kawalec
Drug Management Department, Faculty of Health Sciences, Institute of Public Health, Jagiellonian University, ul. Grzegórzecka 20, 31-531, Kraków, Poland.|Department of Neurobiology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland.
Andrzej
A
Pilc
D006801:Humans; D000068879:Adalimumab / Q000009:adverse effects; D000911:Antibodies, Monoclonal / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects; D001499:Bayes Theorem; D001688:Biological Products / Q000009:adverse effects; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy; D000069285:Infliximab / Q000009:adverse effects; D016032:Randomized Controlled Trials as Topic
D000068879:Adalimumab; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D001688:Biological Products; C529000:golimumab; D000069285:Infliximab; C543529:vedolizumab