Combination therapy for IBD carries higher infection risk than monotherapy

For patients with inflammatory bowel disease (IBD), combination therapy including a tumor necrosis factor (TNF) antagonist is associated with a higher risk of serious infection than monotherapy with an immunosuppressive agent, a recent review found.

The systematic review and meta-analysis included 15 observational studies (>500 person-years) of patients with IBD treated with TNF antagonists, non-TNF targeted biologics, tofacitinib, and/or immunosuppressive agents (thiopurines, methotrexate). All of the studies were published before March 18, 2018, and included serious infections as an outcome. Results were published by Clinical Gastroenterology and Hepatology on March 12.

Compared to anti-TNF monotherapy, risk of serious infection was higher in patients taking a combination of anti-TNF and an immunosuppressive agent (six study cohorts; relative risk [RR], 1.19; 95% CI, 1.03 to 1.37), an anti-TNF and a corticosteroid (four cohorts; RR, 1.64; 95% CI, 1.33 to 2.03), or all three classes together (two cohorts; RR, 1.35; 95% CI, 1.04 to 1.77). Monotherapy with an immunosuppressive agent was associated with a lower risk of infection than anti-TNF monotherapy (seven cohorts; RR, 0.61; 95% CI 0.44 to 0.84) or the combination of an anti-TNF and an immunosuppressive agent (two cohorts; RR, 0.56; 95% CI, 0.39 to 0.81). In patients with ulcerative colitis, infliximab-based therapy was associated with lower risk of serious infections than adalimumab-based therapy (four cohorts; RR, 0.57; 95% CI, 0.33 to 0.97), but this was not true in Crohn's disease (four cohorts; RR, 0.91; 95% CI, 0.49 to 1.70). The authors noted that there was minimal heterogeneity among studies, but limited data were available on the comparative safety of biologic agents that do not inhibit TNF and tofacitinib.

“Taken together, this data suggests that risk of serious infections may be lower with immunosuppressive agents, followed by TNFi [TNF inhibitor] monotherapy and chronic corticosteroids, and the risk is only modestly higher with combination therapy of TNFi [and an immunosuppressive agent],” the authors said. They noted that combination therapy is the most effective therapy and that this benefit could theoretically offset the increased risk of infection.

Among other factors, the analysis was limited by its inclusion of only observational studies; the authors chose to exclude clinical trials because they found the restrictive inclusion criteria not representative of real-world clinical practice. They called for well-designed, comparative, real-world studies of these medications.

“While awaiting such studies, patients at high risk of disease-related complications ought to be treated aggressively as appropriate with combination therapy, rather than conservatively due to fear of serious infections. In contrast, patients at high risk of treatment-related complications such as serious infections and low risk of disease-related complications should be treated cautiously weighing risk and benefit of therapy,” the authors advised.