Tofacitinib for immune-related adverse events ≥ grade 3 induced by immune checkpoint inhibitors: A single-arm, open-label, two-stage study.

81

Background: This study evaluates the efficacy and safety of tofacitinib, a JAK inhibitor, in treating irAEs and explores its feasibility as a bridging strategy to facilitate ICI resumption. Methods: We conducted a single-arm, open-label, two-stage prospective study (Simon design) (registration number: MR-35-26-014338) . Patients who developed grade ≥3 irAEs after ICI treatment at Fujian Cancer Hospital between July 2024 and February 2026, and who were refractory to glucocorticoids, glucocorticoid-dependent, or declined glucocorticoid therapy, were enrolled. Treatment regimen: Tofacitinib 5 mg orally twice daily. Outcomes assessed: irAE response rate, time to response, tumor status, and ICI rechallenge status, among others. Results: Twenty-three patients were enrolled: 13 (56.52%) in Stage 1 and 10 (43.48%) in Stage 2. Median age was 65 years. Baseline characteristics included glucocorticoid resistance (n=15, 65.22%), dependence (n=5, 21.74%), and patient refusal (n=3, 13.04%). Regarding ICI regimens, 11 (47.83%) developed irAEs from monotherapy and 12 (52.17%) from combination immunotherapy. IrAE manifestations included rash (n=16, 69.57%), arthritis (n=3, 13.04%), troponin elevation (n=2, 8.70%), esophagitis (n=1, 4.35%), and gingivitis (n=1, 4.35%). Efficacy assessment showed a 91.30% (21/23) response rate (≥one-grade improvement) for irAEs, with a median time to response of 3 days. Response rates were 87.50% for rash and 100% for all other irAEs. In terms of oncological assessment, except for 1 terminally ill patient and 2 patients with insufficient follow-up who could not be evaluated, the remaining 20 patients achieved a 100% disease stability rate within 8 weeks of tofacitinib treatment. As of the data cutoff, 14 patients had been followed up for more than 20 weeks, with a disease stability rate of 85.71%. Regarding ICI resumption, 10 patients restarted immunotherapy; 6 (60%) received concurrent tofacitinib maintenance. No irAE recurrence was observed (median follow-up 6.0 months, range 2.6–16.0 months). Patients rechallenged with ICI plus tofacitinib maintenance showed 100% disease stability at 8 weeks; among 4 with >20 weeks follow-up, stability was 75%. No tofacitinib-related adverse events, infections, or thromboembolic events occurred in either stage. Conclusions: Tofacitinib demonstrates high response rates and rapid onset for grade ≥3 irAEs that are refractory to, dependent on, or declined by patients in favor of glucocorticoids, while effectively enabling safe ICI resumption with a favorable safety profile. These findings establish tofacitinib as a promising second-line therapeutic option for immune-related adverse events. Clinical trial information: MR-35-26-014338 .