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

Abstract

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.

Clinical outcomes of patients with corticosteroid refractory immune checkpoint inhibitor-induced enterocolitis treated with infliximab

“…In corticosteroid refractory disease, which occurs in over a third of patients, infliximab (IFX), an anti-tumor necrosis factor (TNF) monoclonal antibody, is recommended. 15 These guidelines are predominantly based on expert opinion, and to date, there is a paucity of data informing the appropriate institution of secondline therapies such as IFX. In a recent meta-analysis evaluating anti-inflammatory therapies in CPI-induced enterocolitis, data pooled from 17 studies across 333 patients 15 found that IFX was effective in 81% (95% CI 73% to 87%).…”

“…15 These guidelines are predominantly based on expert opinion, and to date, there is a paucity of data informing the appropriate institution of secondline therapies such as IFX. In a recent meta-analysis evaluating anti-inflammatory therapies in CPI-induced enterocolitis, data pooled from 17 studies across 333 patients 15 found that IFX was effective in 81% (95% CI 73% to 87%). There was evidence that timely initiation of IFX within 10 days of onset of symptoms led to significantly fewer hospitalizations, fewer corticosteroid taper failures, shorter courses of corticosteroid treatment and shorter duration of symptoms.…”

Immune checkpoint inhibitor-induced colitis is mediated by CXCR6+ polyfunctional lymphocytes and is dependent on the IL23/IFNγ axis

“…Two independent studies in different tumour settings, identi ed impaired survival in steroid exposed patients 15,16 . Treatment outcomes with biological therapies, such as anti-TNFα drugs are also heterogeneous 17 , especially if robust outcome measures are used. Not only do many patients fail to achieve steroid-free remission, but side effects also including severe infections were common 18 .…”

The Entire Intestinal Tract Surveillance Using Capsule Endoscopy after Immune Checkpoint Inhibitor Administration: A Prospective Observational Study

“…However, patients with severe symptoms should receive systemic corticosteroids or infliximab, an anti-TNFα antibody. Although there is limited data available from prospective studies with a large sample size, Ibraheim et al reported in the meta-analysis of 39 studies that corticosteroid efficacy was 59% [20]. Additionally, the response to infliximab in patients who are refractory or intolerant to corticosteroids was reported to be 81%, with 1-3 infliximab doses in most cases.…”