Rheumatic immune-related adverse events associated with cancer immunotherapy: A nationwide multi-center cohort

Objective: Although immune checkpoint inhibitors (ICI) have revolutionized cancer therapy, their use is associated with immune toxicities referred to as immune-related adverse events (irAE). Here we describe the clinical presentation and management of rheumatic immune-related adverse events (Rh-irAE) in a national multicenter cohort. Methods: All patients presenting with Rh-irAE at 9 academic sites across Canada between January 2013 and January 2019 were identified and included in this retrospective cohort study. Standardized data were extracted by chart review. Results: 117 patients who developed 136 Rh-irAE were identified. The most frequent Rh-irAE was symmetric polyarthritis (n = 45). Other Rh-irAE included non-inflammatory musculoskeletal symptoms (n = 18), polymyalgia rheumatica (n = 17) and myositis (n = 9). Prednisone was the most commonly used treatment (n = 76) with a mean maximum dose of 60 +/- 74 mg/d and duration of treatment of 8.4 +/- 11 months. Forty-two patients required conventional synthetic disease-modifying anti-rheumatic drugs (DMARD) and two required biologic DMARD to control the Rh-irAE. ICI was discontinued due to the Rh-irAE in 22 patients. There were no deaths related to Rh-irAE. Treatment of the Rh-irAE did not appear to negatively impact the tumor response to immunotherapy with 23 patients experiencing tumor progression prior to treatment of the Rh-irAE and 13 following treatment. Conclusion: In this largest multi-center cohort of Rh-irAE described to date, symmetric polyarthritis was the most common Rh-irAE. There was considerable heterogeneity of treatment, although this did not appear to negatively impact the anti-tumor response. This study can inform the development of evidence-based recommendations to optimize Rh-irAE and cancer outcomes in patients treated with ICI.