Exploratory Clinical Study to Evaluate the Efficacy and Safety of Sulfasalazine for Immune Checkpoint Inhibitor (ICI)-Induced Colitis.

Background: The first-choice treatment for immune checkpoint inhibitor (ICI)-induced colitis is steroids; however, side effects may occur and survival may be reduced. Sulfasalazine (SSZ) is primarily used for inflammatory bowel disease but studies on ICI-induced colitis are scarce. This study examined the efficacy and safety of SSZ for ICI-induced colitis while testing SSZ as a steroid-sparing agent. Methods: This study (iRECSA) was a single-arm, multicenter exploratory study from November 2021 to December 2024 that evaluated the efficacy and safety of SSZ for mild-to-moderate ICI-induced colitis. SSZ was given at 4 g/day orally for 2 weeks. The primary outcome was clinical response (a ≥ 1-point reduction from baseline partial Mayo score or partial Mayo score < 1). Secondary endpoints included clinical responses in the Simple Clinical Colitis Activity Index (SCCAI), Lichtiger Index, and Common Terminology Criteria for Adverse Events (CTCAE) grade, plus SSZ-related adverse event incidence. Results: Ten patients were enrolled. The median partial Mayo score decreased from 4 (range 3-5) to 2 (range 0-4), with 80% of patients achieving a clinical response. Similar response rates were observed with the Lichtiger Index and CTCAE grade. Defecation urgency was present in 70% of patients at baseline but resolved in all after treatment. Nine adverse events occurred in six patients; three patients discontinued SSZ because of hypersensitivity-related adverse events. Three patients required systemic steroids after the study treatment. Conclusions: This exploratory study suggests that SSZ may be a useful option for mild-to-moderate ICI-induced colitis, but caution is warranted against SSZ-related hypersensitivity.