Introduction: Immune checkpoint inhibitors (CPI) have changed the landscape in cancer treatment and are becoming the standard of care for many cancer types. CPIs block the inhibitory pathway of T-Cell activation, leading to immune response directed against tumours and potential for disease regression. However, a well-known inadvertent effect is the development of autoreactivity, with subsequent immune related adverse events (irAEs). IrAEs have been reported in almost all organ systems. Whereas gastrointestinal and endocrinological irAEs have been widely studied, inflammatory arthritis (ir-IA) has gained less attention, although it can be debilitating for patients. This retrospective observational study aims to examine prevalence of ir-IA, clinical course, including treatment and long-term outcomes of ir-IA.
Method: We retrospectively assessed for clinical characteristics of de novo immune checkpoint inhibitor induced inflammatory arthritis within a cohort of 871 patients who received checkpoint inhibitors at a tertiary hospital in Australia, from January 2015 to December 2019.
Results: We found 20 patients (2.2%) who fit the criteria. Mean time to develop ir-IA was 18.8 weeks. 11 out of 20 patients had autoantibodies collected - 8 were seronegative, 3 were seropositive (1 ACPA positive, 2 dual RF and ACPA positive). 7 patients had complete resolution of ir-IA while 13 patients had persistent ir-IA requiring long term therapy. 18 out of the 20 patients received high dose corticosteroids for initial management. 11 patients were referred for management by rheumatologist and 9 patients were managed by oncologist. The mean dose of systemic prednisolone commenced in the group of patients who were referred to rheumatology was 14.1mg and 53.3mg in the group of patients who were managed by oncology, respectively (95% CI:12.92 – 65.57, p = 0.0058). csDMARDs were commenced in 10 out of 11 patients managed by rheumatologist and all experienced positive response to therapy.
Conclusion: This retrospective study supports that a subset of patients exposed to a CPI may develop inflammatory arthritis. ir-IA appears to be of slower onset than other irAEs and most patients were seronegative. The ir-IA typically persists after cessation of the CPI and most patients required long-term maintenance therapy. Early referral of these patients to a rheumatology service is essential as it avoided long term exposure of high dose corticosteroids exposure with commencement of DMARD therapy to control disease. Further studies are needed to evaluate superiority of different DMARDs in the treatment of ir-IA given this is becoming an increasingly common phenomenon.