Background/Purpose: Immune checkpoint inhibitors (ICIs) have emerged as an important treatment for advanced malignancies. ICIs are a form of immunotherapy which block negative co-stimulation of T-cells, thereby causing generalized immune activation. De novo inflammatory arthritis (IA) is a potential consequence of ICI use, but there is limited information to guide management of this often severe immune-related adverse event.

Methods: We evaluated clinical data from our longitudinal cohort of patients with ICI-induced IA. Patients with rheumatologist-confirmed IA occurring during or after ICI treatment with no prior history of IA or other systemic autoimmune disease were included. Patients were excluded if they were missing initial joint counts/description of clinical phenotype, or their ICI agent was unknown (e.g. blinded clinical trial). Data was analyzed by ICI treatment regimen to evaluate for differences in presentation and treatment response.

Results: Of the 31 patients included, 18 received anti-PD-1 or anti-PD-L1 monotherapy, 13 received anti-CTLA-4/anti-PD-1 combination therapy and none received anti-CTLA-4 monotherapy (table 1). Median age was 59, and 41.9% were female. Melanoma and non-small cell lung cancer were the most common tumors. Eighty-four percent (26/31) required systemic immunosuppression (corticosteroids, DMARDs). The other 5 patients received NSAIDs and intra-articular steroids. Initial joint involvement and CRP differed significantly by treatment regimen; those treated with combination therapy had higher CRP levels and were less likely to have initial small joint involvement. All cases of reactive arthritis (arthritis plus urethritis/conjunctivitis) were in the combination therapy group. Six patients received therapy with TNF-inhibitors (TNF-i), 4 received methotrexate, and 1 received leflunomide. Of those treated with TNFi, 4 had a persistent anti-tumor response to ICIs, and none lost the response while on TNF-inhibition. Duration of treatment with TNFi ranged from 2-21 months. 3-month follow up data was available on 20 patients after cessation of ICIs (7 still on therapy, 4 died/lost to follow up). Of these 18 had continued IA symptoms requiring treatment.

Conclusion: Baseline clinical features of ICI-induced IA differ by ICI regimen, specifically CRP levels, initial joints affected, and presence of the reactive arthritis triad. The majority of patients referred to rheumatology required systemic immunosuppression to manage their IA symptoms. Tumor progression was not seen in patients requiring TNFi.