Safety profile of biologic drugs in the therapy of Crohn disease: A systematic review and network meta-analysis.
BACKGROUND
Crohn disease (CD) is an inflammatory bowel disease which occurs especially in developed countries of Western Europe and North America. The aim of the study was to compare the safety profile of biologic drugs in patients with CD.


METHODS
A systematic literature search was performed using PubMed, Embase, and CENTRAL databases, until April 27, 2016. We included randomized controlled trials (RCTs) that compared the safety of biologic drugs (infliximab, adalimumab, vedolizumab, certolizumab pegol, and ustekinumab) with one another or with placebo in patients with CD. The network meta-analysis (NMA) was conducted for an induction phase (6-10 weeks) and maintenance phase (52-56 weeks) with a Bayesian hierarchical random effects model in the ADDIS®software. The PROSPERO registration number was CRD42016032606.


RESULTS
Ten RCTs were included in the systematic review with NMA. In the case of the induction phase, the NMA could be conducted for the assessment of the relative safety profile of adalimumab, vedolizumab, certolizumab pegol, and ustekinumab, and in the case of the maintenance phase-of infliximab, adalimumab, and vedolizumab. There were no significant differences in the rate of adverse events in patients treated with biologics. Statistical analysis revealed that vedolizumab had the greatest probability of being the safest treatment in most endpoints in the induction phase and adalimumab-in the maintenance phase.


CONCLUSIONS
No significant differences between the biologics in the relative safety profile analysis were observed. Further studies are needed to confirm our findings, including head-to-head comparisons between the analyzed biologics.
Drug Management Department, Institute of Public Health, Faculty of Health Sciences, Jagiellonian University Medical College, Kraków, Poland.
Paweł
P
Moćko
Drug Management Department, Institute of Public Health, Faculty of Health Sciences, Jagiellonian University Medical College, Kraków, Poland. Electronic address: pawel.kawalec@uj.edu.pl.
Paweł
P
Kawalec
Institute of Pharmacology, Polish Academy of Sciences, Department of Neurobiology, 31-343 Kraków, Smętna street 12, Poland.
Andrzej
A
Pilc
D000068879:Adalimumab / Q000009:adverse effects / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000627:therapeutic use; D001688:Biological Products / Q000009:adverse effects / Q000627:therapeutic use*; D003424:Crohn Disease / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology; D006801:Humans; D000069285:Infliximab / Q000009:adverse effects / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic / Q000379:methods*
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D001688:Biological Products; C543529:vedolizumab; D000069285:Infliximab; D000068879:Adalimumab
Biologic drugs; Crohn disease; Network meta-analysis; Safety profile; Systematic review