Comparative Risk of Serious Infections With Biologic and/or Immunosuppressive Therapy in Patients With Inflammatory Bowel Diseases: A Systematic Review and Meta-Analysis

Abstract

This article has an accompanying continuing medical education activity, also eligible for MOC credit, on page e7. Learning Objective-Upon completion of this activity, successful learners will be able to list the relative risk of serious infection with various treatment strategies in patients with inflammatory bowel disease; and in addition to biologic and immunomodulator therapies, list risk factors for serious infections in patients with inflammatory bowel diseases. BACKGROUND & AIMS: We performed a systematic review and meta-analysis to evaluate the comparative risk of serious infections with tumor necrosis factor (TNF) antagonists, non-TNF targeted biologics, tofacitinib, and immunosuppressive agents in patients with inflammatory bowel diseases (IBDs). METHODS: In a systematic search of publications, through March 18, 2018, we identified 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) that reported risk of serious infections. Only studies with active comparators were included, to allow appropriate comparative synthesis. We performed random-effects meta-analysis and estimated relative risk (RR) and 95% CIs. RESULTS: Compared with anti-TNF monotherapy, risk of serious infection increased with the combination of anti-TNF and an immunosuppressive agent (in 6 cohorts: RR, 1.19; 95% CI, 1.03-1.37), with anti-TNF and a corticosteroid (in 4 cohorts: RR, 1.64; 95% CI, 1.33-2.03), or with all 3 drugs (in 2 cohorts: RR, 1.35; 95% CI, 1.04-1.77); there was minimal heterogeneity among studies. In contrast, monotherapy with an immunosuppressive agent was associated with a lower risk of serious infections than monotherapy with a TNF antagonist (7 cohorts: RR, 0.61; 95% CI 0.44-0.84) or a TNF antagonist with an immunosuppressive agent (2 cohorts: RR, 0.56; 95% CI, 0.39-0.81). Infliximab-based therapy was associated with a lower risk of serious infections compared with adalimumab-based therapy in patients with ulcerative colitis (4 cohorts: RR, 0.57; 95% CI, 0.33-0.97), but not Crohn's disease (4 cohorts: RR, 0.91; 95% CI, 0.49-1.70). Few data were available on the comparative safety of biologic agents that do not inhibit TNF and tofacitinib. CONCLUSIONS: Combination therapies for IBD that include TNF antagonists, especially with corticosteroids, are associated with a higher risk of serious infection, whereas monotherapy with an immunosuppressive agent is associated with a lower risk, compared with monotherapy with a TNF antagonist. Studies are needed to evaluate the comparative safety of non-TNF targeted biologics and small molecules for treatment of IBD.

COVID-19 with rheumatic diseases: a report of 5 cases

“…One of the RA patients was treated with Methotrexate during the entire period of hospitalization, and her condition remained stable. According to a study, coadministration of Methotrexate and Hydroxychloroquine did not result in an increased risk of hospitalization due to infection [7]. In the present report, a 79-year-old male patient with SSc progressed to critical COVID-19, and this may be explained by The texture of both lungs is disordered, the transparency is increased, some of them have reticular changes, multiple patchy ground glass density shadow and fuzzy edge are seen in both lungs.…”

COVID-19 and immunomodulation in IBD

“…Several immunotherapies in patients with IBD have been associated with an increased risk of infections as they may inhibit intracellular signalling cascades needed for the host to fight pathogens. [55][56][57] Corticosteroids, for instance, are potentially associated with an increased risk for infections and have been widely used in studies from China for treatment of ARDS and hyperinflammation in covid-19. Although these studies were not designed to evaluate the effects of steroids, one study even suggested that treatment with methylprednisolone decreases the risk of death in covid-19.…”

Review article: prevention, diagnosis and management of COVID‐19 in the IBD patient

“…Anti‐TNF agents have been shown to increase the risk of upper and lower respiratory tract infections, as well as serious and opportunistic pulmonary infections 62,75,76 . Compared with anti‐TNF monotherapy, risk of serious infections increases with combination of anti‐TNF and an immunosuppressive agent or most significantly in combination with corticosteroids 77 . In a study that did not separate mono—or combination—anti‐TNF therapies, the risk of pneumonia was only slightly increased in patients receiving a TNF antagonist (OR: 1.28, 95% CI [1.08‐1.52]) 62 …”