Baseline predictors of disease severity in immune checkpoint inhibitor-induced inflammatory arthritis

Abstract

Objectives: The objective of this study was to determine baseline risk factors for requiring immunosuppression and having persistent arthritis in patients with immune checkpoint inhibitor-induced inflammatory arthritis (ICI-inflammatory arthritis).

Methods: Participants were adults with rheumatologist diagnosed ICI-inflammatory arthritis. The primary outcome was requirement of conventional synthetic (cs) or biologic (b) DMARDs; other outcomes were persistence of inflammatory arthritis >6 months after ICI cessation and requirement of CSs. Logistic regression models evaluated associations between clinical features and primary and secondary outcomes, with adjustment for potential confounders, as appropriate.

Results: One hundred and twenty-six patients with ICI-inflammatory arthritis were included; 53 patients (42%) required a csDMARD/bDMARD. In the univariate logistic regression analysis, higher clinical disease activity index (CDAI), tenosynovitis, longer symptom duration before first rheumatology visit and longer ICI duration were significantly associated with a higher likelihood of requiring DMARDs; in addition, there was a trend towards those treated with prior chemotherapy being less likely to need DMARDs. After adjustment, tenosynovitis, longer symptom duration and higher CDAI remained associated with requiring DMARDs, while those with prior chemotherapy were significantly less likely to require DMARDs. Combination anti-CTLA-4 (cytotoxic T-lymphocyte-associated protein-4)/PD-1 (Programmed cell death protein-1) therapy and CS use at baseline were associated with a higher risk of persistent inflammatory arthritis.

Conclusion: Higher levels of disease activity, tenosynovitis and longer symptom duration prior to rheumatology referral were associated with requiring DMARDs for ICI-inflammatory arthritis, while those treated previously with chemotherapy were less likely to require additional immunosuppression. The presence of risk factors for severe disease at baseline may indicate a role for higher initial CS dose, earlier rheumatology referral, and adoption of immunosuppression beyond CSs to improve outcomes.

Keywords: cancer; immune checkpoint inhibitor; immunotherapy; inflammatory arthritis.