COLAR: open-label clinical study of IL-6 blockade with tocilizumab for the treatment of immune checkpoint inhibitor-induced colitis and arthritis

• DOI: 10.1136/jitc-2022-005111
• Publication Date: 2022-09-12T15:37:04Z
• Authors: Rikke Boedker Hol...; Ole Haagen Nielsen; Søren Jacobsen; Lene Buhl Riis; Susann Theile; Jacob Tveiten Bje...; Peter Vilmann; Julia Sidenius Jo...; Mogens Karsbøl Bo...; Rikke Helene Løve...; Inge Marie Svane; Dorte Lisbet Nielsen; Inna Markovna Chen
• Keywords: Tocilizumab; Clinical endpoint

Background Immune-related adverse events due to immune checkpoint inhibitors (ICIs) are not always effectively treated using glucocorticoids and it may negatively affect the antitumor efficacy of ICIs. Interventional studies alternatives lacking. We examined whether interleukin-6 blockade by tocilizumab reduced ICI-induced colitis arthritis. Patients methods with solid cancer experiencing Common Terminology Criteria for Adverse Events (CTCAE v5.0) grade >1 colitis/diarrhea (n=9), arthritis or both (n=2) were recruited (8 mg/kg) every 4 weeks until worsening unacceptable toxicity. allowed receive systemic other immunosuppressive drugs within 14-day screening period. The primary endpoint was clinical improvement arthritis, defined as ≥1 CTCAE reduction 8 weeks. Secondary endpoints improvements glucocorticoid-free remission at week 24; safety; radiologic, endoscopic, histological changes; changes in plasma concentrations C reactive protein, cytokines (IL-6, IL-8, IL-17), YKL-40. Results Nineteen patients available analysis; one patient excluded pancreatic insufficiency-induced diarrhea. received treatment pembrolizumab (n=10) nivolumab (n=4) monotherapy ipilimumab (n=5) combined. Seven had been initially glucocorticoids, two them also infliximab. Ten continued ICI therapy during treatment. achieved 15 19 (79%) patients. Additional 10, another stabilized symptoms. At 24, ongoing without (n=12), including complete (n=10), noted. Five grades 3–4 treatment-related events, which manageable reversible. Conclusions Tocilizumab showed promising a safety profile Our findings support feasibility randomized trials immune-related events. Trial registration number NCT03601611 .