Systematic review with meta‐analysis: effectiveness of anti‐inflammatory therapy in immune checkpoint inhibitor‐induced enterocolitis

Summary Background Immune checkpoint inhibitors have revolutionised cancer treatment, but at the cost of off‐target immune‐mediated organ damage. This includes checkpoint inhibitor‐induced enterocolitis which frequently requires hospitalisation and may be life‐threatening. Empiric treatment typically includes corticosteroids and infliximab, although no large‐scale studies have confirmed their effectiveness. Aim To investigate the effectiveness of anti‐inflammatory therapy in checkpoint inhibitor‐induced enterocolitis Methods We performed a systematic review and meta‐analysis of studies reporting clinical outcomes of checkpoint inhibitor‐induced enterocolitis in adult cancer patients treated with anti‐inflammatory agents. We searched Medline, EMBASE, and the Cochrane library through April and extracted the proportion of patients responding to anti‐inflammatory therapy. Variation in effect size was studied using a random‐effects meta‐regression analysis, with checkpoint inhibitor agent and tumour type as the variables. Results Data were pooled from 1210 treated patients across 39 studies. Corticosteroids were effective in 59% (95% CI 54‐ 65) of patients, with response significantly more favourable in patients treated with anti‐PD‐1/L1 monotherapy, compared with anti‐CTLA‐4 containing regimens (78%, 95% CI 69‐85 vs 56 %, 95% CI 49‐63, P = 0.003), and more favourable in lung cancer patients compared with melanoma patients (88%, 95% CI 62‐97 vs 55%, 95% CI 47‐63, P = 0.04). Infliximab was effective in 81% (95% CI 73‐87) of patients, and vedolizumab in 85% (95% CI 60‐96). Conclusion Corticosteroids, infliximab and vedolizumab, are effective in the treatment of checkpoint inhibitor‐induced enterocolitis. Checkpoint inhibitor regimen and cancer type were significant moderators in response to corticosteroid therapy.