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Background: The aim of this retrospective study was to evaluate the dual efficacy of tocilizumab (TCZ) in the treatment of immune checkpoint inhibitor (ICI)-associated arthritis (ICI-AR) and the prevention of relapses after rechallenge., Patients and Methods: We identified 26 patients with ICI-AR. The primary objectives were to evaluate TCZ efficacy in ICI-AR treatment and as secondary prophylaxis during ICI rechallenge in 11 of them. Patients received prednisone (CS) at 0.3 mg/kg tapered at 0.05 mg/kg weekly for six weeks. TCZ was administered at a dose of 8 mg/kg every 2 weeks. In the subgroup receiving secondary prophylaxis (rechallenge n = 11), TCZ was reintroduced with the same regimen concurrently with ICI rechallenge, and without the addition of CS. A control group of patients (rechallenge n = 5) was rechallenged without TCZ. Secondary endpoints included post-rechallenge evaluation of ICI duration, reintroduction of CS >0.1 mg/kg/day, ICI-AR flares, and disease control rate., Results: The median age of the patients was 70 years. The median follow-up from ICI initiation was 864 days. Among the 20 patients treated with TCZ for ICI-AR, all (100%) achieved an ACR70 response rate, defined as greater than 70% improvement, at 10 weeks. Some 81% of these patients achieved steroid-free remission after 24 weeks on TCZ. The median follow-up period was 552 days in rechallenged patients. The results demonstrated a reduction in ICI-AR relapses upon ICI rechallenge in patients receiving TCZ prophylaxis compared with patients who did not receive prophylaxis (17% versus 40%). The requirement for CS was completely abolished with prophylaxis (0% versus 20%), and the mean duration of ICI treatment was notably extended from 113 to 206 days. The 12-month post-rechallenge outcomes showed a disease control rate of 77%. During TCZ prophylaxis, CXCL9 remained elevated, showing no decline from their concentrations at the onset of ICI-AR., Conclusions: In addition to treating ICI-AR, TCZ demonstrated efficacy as a secondary prophylactic agent, preventing the recurrence of symptoms and lengthening ICI treatment duration after ICI rechallenge., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)