Systematic review with meta-analysis: safety and tolerability of immune checkpoint inhibitors in patients with pre-existing inflammatory bowel diseases

Abstract

Background: Immune checkpoint inhibitors may variably impact patients with pre-existing autoimmune diseases.

Aims: To evaluate the risks and outcomes of adverse events in patients with pre-existing inflammatory bowel diseases treated with immune checkpoint inhibitors.

Methods: Through a systematic literature review up until July 31, 2020, we identified 12 studies reporting the impact of immune checkpoint inhibitors in 193 patients with inflammatory bowel disease. Outcomes of interest were relapse of inflammatory bowel disease, need for corticosteroids and/or biologics to manage inflammatory bowel disease relapse, and discontinuation of immune checkpoint inhibitors. We calculated pooled rates (with 95% confidence intervals [CI]) using random effects meta-analysis, and examined risk factors associated with adverse outcomes through qualitative synthesis of individual studies.

Results: On meta-analysis, 40% patients (95% CI, 26%-55%) experienced relapse of inflammatory bowel disease with immune checkpoint inhibitors. Among patients who experienced relapse, 76% (95% CI, 65%-85%) required corticosteroids, and 37% (95% CI, 22%-53%) required biologic therapy. Overall, 35% patients (95% CI, 17%-57%) with inflammatory bowel disease discontinued immune checkpoint inhibitors. Gastrointestinal perforation and abdominal surgery due to immune checkpoint inhibitor complications occurred in <5% patients. In a large study, inhibitors of cytotoxic T-lymphocyte antigen-4 (CTLA-4) were associated with a higher risk of relapse than programmed cell death 1 (PD-1) and programmed death ligand 1 (PD-L1) inhibitors.

Conclusions: Approximately 40% of patients with pre-existing inflammatory bowel diseases experience relapse with immune checkpoint inhibitors, with most relapsing patients requiring corticosteroids and one-third requiring biologics. CTLA-4 inhibitors may be associated with higher risk of relapse.

Figure 1.

Study selection flowchart

Figure 2.

Pooled rate (and 95% confidence interval) of relapse of IBD after initiation of treatment with immune checkpoint inhibitor, using double arcsine transformation, based on 12 studies with 193 patients

Figure 3:

Pooled rate (and 95% confidence interval) of need for corticosteroids in patients with IBD experiencing relapse after initiation of treatment with immune checkpoint inhibitor, using double arcsine transformation, based on 6 studies with 68 patients

Figure 4:

Pooled rate (and 95% confidence interval) of need for biologics in patients with IBD experiencing relapse after initiation of treatment with immune checkpoint inhibitor, using double arcsine transformation based on 6 studies with 67 patients

Figure 5:

Pooled rate (and 95% confidence interval) of need to discontinue immune checkpoint inhibitor in patients with pre-existing IBD, using double arcsine transformation, based on 8 studies with 173 patients