No abstract

Checkpoint inhibitors are a first-line therapy for advanced melanoma, though their use is limited by diarrhea and colitis. The aim of our study was to determine the risk of these toxicities associated with immunotherapy in advanced melanoma. Electronic databases were searched through June 2017 for prospective studies reporting the risk of diarrhea and colitis in advanced melanoma treated with anti-programmed death-1 (PD-1) or anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4) inhibitors. Standardized definitions assessed the grade of diarrhea and colitis. Pooled incidence and weighted relative risk estimates with 95% confidence intervals (CI) were estimated using random effects model. Eighteen studies were included: 6 studies (1537 patients) with PD-1 inhibitors and 15 studies (3116 patients) with CTLA-4 inhibitors. The incidence of all-grade diarrhea was 13.7% (95% CI, 10.1%-17.2%) for anti-PD-1 and 35.4% (95% CI, 30.4%-40.5%) for anti-CTLA-4. The incidence of all-grade colitis was 1.6% (95% CI, 0.7%-2.4%) for anti-PD-1, and 8.8% (95% CI, 6.1%-11.5%) for anti-CTLA-4. When PD-1 inhibitors were compared directly with CTLA-4 inhibitors, the relative risk of all-grade diarrhea was 0.58 (95% CI, 0.43-0.77), and the relative risk of all-grade colitis was 0.16 (95% CI, 0.05-0.51). The rate of therapy discontinuation was numerically higher for anti-CTLA-4 therapy compared with anti-PD-1 therapy. Finally, 2 studies compared combination immunotherapy with anti-CTLA-4 therapy alone. The relative risk of developing all-grade diarrhea and colitis with combination therapy was 1.31 (95% CI, 1.09-1.57) and 1.21 (95% CI, 0.73-1.99), respectively. Diarrhea and colitis are frequent toxicities associated with checkpoint inhibitors, and seem to be most common with CTLA-4 inhibitors.

BackgroundInflammatory bowel diseases (IBD) and asthma share genetic and environmental risk factors. Consequently, several observational studies have explored an association between IBD and asthma. We systematically reviewed and summarized the literature on the co-occurrence of asthma and IBD.MethodsMEDLINE and EMBASE (to April 2017) were searched to identify observational studies on the association between asthma and IBD. Relative risks (RR) were pooled using random effects models. Heterogeneity was assessed using the I2 and Cochran Q statistics. Meta-regression based on study design, source of patients (population-based vs. tertiary-care center) and study location was conducted to explain between-study heterogeneity.ResultsEighteen studies were identified (15 Crohn’s disease, 15 ulcerative colitis (UC)). Asthma was associated with both Crohn’s disease (pooled RR 1.30, 95% confidence interval (CI) 1.16–1.47, I2 = 88%) and UC (RR 1.34, 95% CI 1.24–1.44, I2 = 93%). The study design and source of patients and study location explained between-study heterogeneity in Crohn’s disease, but not UC.ConclusionAsthma is associated with both Crohn’s disease and UC. Additional research is needed to determine if one disease influences the risk of developing the other or if the frequent co-occurrence of these diseases result from shared genetic, environmental, and microbial risk factors.