Treating inflammatory bowel disease with biologic therapies increases the risk of opportunistic infections but not the risk of serious infections, based on a systematic review and meta-analysis reported in the October issue of Clinical Gastroenterology and Hepatology.
Contrary to common belief, infection risk seemed similar with the integrin and anti–tumor necrosis factor classes, said Stefanos Bonovas, MD, MSc, PhD, of Humanitas Clinical and Research Center, Milan, with his associates. Clinicians and patients can use these findings to better weigh the risks and benefits of biologic therapies for IBD, although “studies in real-world settings, national and international registries, and clinical audits may serve as complementary data sources to further assess biologic treatments’ comparative and long-term safety profiles,” the researchers added.
Biologics can effectively manage IBD but raise concerns about infection and malignancy. To examine these risks in adults with IBD, the researchers systematically searched PubMed, Embase, Scopus, the Cochrane IBD Group Specialized Trials Register, the World Health Organization International Clinical Trials Registry Platform, and clinicaltrials.gov through March 2016 for randomized, placebo-controlled or head-to-head trials of approved IBD therapies, including adalimumab, certolizumab, golimumab, infliximab, natalizumab, and vedolizumab. After excluding systematic reviews, uncontrolled trials, and secondary analyses, 49 trials of 14,590 patients remained for meta-analysis, the investigators said (Clin Gastroenterol Hepatol. 2016 May 4. doi: 10.1016/j.cgh.2016.04.039).
Biologic therapy conferred a “moderate increase” in the likelihood of any infection, with an odds ratio of 1.19 when compared with patients who did not receive biologics (95% confidence interval, 1.10-1.29), the researchers said. The risk of opportunistic infections was somewhat higher (OR, 1.90; 95% CI, 1.21-3.01). However, biologic therapy did not significantly heighten the risk of serious infections, which most studies defined as infections leading to hospitalization, intravenous antibiotic treatment, or death (OR, 0.89; 95% CI, 0.71-1.12). “On the contrary, biologics appeared to significantly reduce risk of serious infections in studies with low risk of bias (OR, 0.56; 95% CI, 0.35-0.90),” the investigators wrote. They did not find an increased risk of malignancy with biologic therapy (OR, 0.90; 95% CI, 0.54-1.50), “but [these] data were insufficient in terms of exposure and follow-up times,” they added.
Comparisons of individual agents and classes also did not reveal any significant associations with the risk of infection, the investigators noted. They did acknowledge several limitations. None of the trials were head-to-head comparisons between biologics, and many were industry funded. Estimates of comparative harm were based on indirect comparisons, and therefore merited cautious interpretation. Because the trials were carried out for regulatory purposes, they enrolled highly selected and homogeneous cohorts of IBD patients, leading to underrepresentation of high-risk and elderly individuals, the researchers noted. “Finally, the exposure and follow-up times were up to 24 months, a time period that is considered sufficient when analyzing infectious adverse effects but wholly insufficient for cancer outcomes. With this in mind, we must look to large register-based cohort studies to enhance our understanding of the biologics-cancer association, despite the biases inherent in observational study designs.”
Dr. Bonovas had no disclosures, while three coauthors reported relationships with a number of pharmaceutical companies.
