Objective We sought to investigate the long-term outcomes of patients who develop immune checkpoint inhibitor (ICI)-induced inflammatory arthritis (IA), to define factors associated with IA persistence after ICI cessation, the need for immunosuppressants and the impact of these medications on underlying malignancies.
Methods We conducted a prospective observational study of patients referred for IA associated with ICIs. Patients were recruited from June 2015 to December 2018. Information was obtained at the baseline visit, and follow-up visits occurred at varying intervals for up to 24 months from ICI cessation. Kaplan-Meier curves were developed to characterise IA persistence. Cox proportional hazards models were used to assess the influence of various factors on IA persistence. Logistic regression was used to evaluate the impact of IA treatment on tumour response.
Results Sixty patients were monitored with a median follow-up after ICI cessation of 9 months. A majority (53.3%) had active IA at their most recent follow-up. IA was less likely to improve in those with longer duration of ICI use, in those receiving combination ICI therapy, and in patients with multiple other immune-related adverse events. Tumour response did not appear to be impacted by immunosuppression. Although not statistically significant, persistent IA was correlated with a better tumour response (complete or partial response).
Conclusion ICI-induced IA can become a long-term disease necessitating management by rheumatology for immunomodulatory treatment. Importantly, the use of immunomodulatory treatment has not been shown to impact cancer outcomes in this study.
- Autoimmune Diseases
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Handling editor Josef S Smolen
AAS and LCC contributed equally.
Contributors LCC, TJB, AAS and COB III designed the study, acquired and analysed data. All authors were involved in interpretation of data. All authors drafted and edited the manuscript.
Funding The database supporting this study was funded in part through a grant from Bristol-Myers Squibb. Additional support was received from an arthritis fellowship award from AbbVie. Additional support was received from the Camille Julia Morgan Arthritis Research and Education fund, the Jerome L. Greene Foundation, and Core B of P30-AR070354 from the National Institutes of Health (NIH).
Disclaimer These sponsors had no role in study design, data analysis or the decision to publish.
Competing interests Individual sources of potential conflict are as follows: JRB: Consultant/Advisory Boards: Bristol-Myers Squibb, Celgene, Lily Merck, Genentech, Amgen, Janssen, Syndax. Grant/Research Funding: Bristol-Myers Squibb, Merck, MedImmune/AstraZeneca. PMF: Consultant/Advisory Board: Abbvie AstraZeneca, Boehringer, Bristol-Myers Squibb, Celgene, Eli Lilly, Novartis. Grant/Research Funding: AstraZeneca, BMS, Corvus, Kyowa, Novartis. DL: Consultant/Advisory Board: Bristol-Myers Squibb, Merck. Grant/Research Funding: Bristol-Myers Squibb, Merck, Aduro Biotech. Honoraria: Merck. EJL: Consultant/Advisory Board: Bristol-Myers Squibb, Novartis, EMD Serono, Array BioPharma, Macrogenics, Merck, Millennium. Grant/Research Funding: Bristol-Myers Squibb, Merck, Sysmex. Patent/Royalty/Intellectual Property: Method of prevent organ transplant rejection using agonist to the PD-1 checkpoint pathway. JN: Consulting/Advisory Board: AstraZeneca, Roche/Genentech, Bristol-Myers Squibb. Grant/Research Funding: Merck, AstraZeneca. Honoraria: Bristol-Myers Squibb, AstraZeneca. LZ: Consultant/Advisory Boards: Biosynergics, Alphamab, Mingrui, Foundation Medicine, NovaRock Biological, Datareve. Grant/Research Funding: Halozyme, iTeos, Bristol-Myers Squibb, Merck, Amgen, NovaRock. Licensing Agreement: Aduro Biotech (given up personal royalty). COB III: Consultant/Advisory Board: Bristol-Myers Squibb, Genentech/Roche, Regeneron/Sanofi. Grant/Research Funding: Bristol-Myers Squibb. AAS: Consultant/Advisory Board: Bristol-Myers Squibb. LCC: Consultant/Advisory Board: Regeneron/Sanofi. Grant/Research Funding: Bristol-Myers Squibb.
Patient consent for publication Not required.
Ethics approval This study was approved by the Johns Hopkins Institutional Review Board IRB00123172.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement Data are available on reasonable request.
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