Immune Checkpoint Inhibitor-Induced Inflammatory Arthritis Persists With Immunotherapy Cessation

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Researchers evaluated the outcomes of patients with immune checkpoint inhibitor-induced inflammatory arthritis and assessed the risk factors for long-term disease requiring immunomodulatory treatment.

Among patients who develop immune checkpoint inhibitor (ICI)-induced inflammatory arthritis (IA), there is a significant risk for long-term disease that requires immunomodulatory treatment, according to study results published in the Annals of the Rheumatic Diseases.

The study included patients (n=60) referred for IA-associated ICIs from June 2015 to December 2018. Researchers collected patient data at baseline with follow-up occurring at various intervals for up to ≤24 months after ICI cessation. They also developed Kaplan-Meier curves to characterize IA persistence and Cox proportional hazards models to assess the influence of different factors on IA persistence. Researchers used logistic regression to determine the effect of IA treatment on tumor response.

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After ICI cessation, the median follow-up was 9 months. At their most recent follow-up, 53.3% of patients had active IA. Results of the univariate analysis indicated that patients were less likely to have IA improvement if they had longer duration of ICI use (hazard ratio [HR], 0.93; 95% CI, 0.87-0.99; P =.02), received combination ICI therapy (HR, 0.29; 95% CI, 0.12-0.72; P =.008), or had a history of other immune-related adverse events (HR, 0.61; 95% CI, 0.39-0.95; P =.03). In the multivariate analysis, the duration of ICI treatment and combination ICI therapy were significant (HRs, 0.82 and 0.06; 95% CI, 0.73-0.92 and 0.01-0.50; P =.001 and P =.009, respectively).

Study results also indicated that immunosuppression may not have affected tumor response; although persistent IA had a correlation with a positive complete or partial antitumor response, it was not statistically significant.

Study limitations included a possible selection bias for patients who were more symptomatic, excluded from the analysis if they were part of a blinded clinical trial or were receiving an investigational immunotherapy agent. Researchers also noted that the conclusions about the association between tumor response and persistent arthritis was limited because not all patients had response evaluation criteria in solid tumors (RECIST) scoring.

“Continued clinical and translational investigation on larger longitudinal cohorts will allow for increased understanding of pathophysiology and determination of the best clinical care for patients with ICI-induced IA,” the researchers wrote.

Disclosure: This clinical trial was supported by Bristol-Myers Squibb Company and AbbVie Inc. Please see the original reference for a full list of authors’ disclosures.


Braaten TJ, Brahmer JR, Forde PM, et al. Immune checkpoint inhibitor-induced inflammatory arthritis persists after immunotherapy cessation [published online September 19, 2019]. Ann Rheum Dis. doi:10.1136/annrheumdis-2019-216109