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Observational Study
. 2020 Mar;79(3):332-338.
doi: 10.1136/annrheumdis-2019-216109. Epub 2019 Sep 20.

Immune checkpoint inhibitor-induced inflammatory arthritis persists after immunotherapy cessation

Tawnie J Braaten  1 , Julie R Brahmer  2 , Patrick M Forde  2 , Dung Le  2 , Evan J Lipson  2 , Jarushka Naidoo  2 , Megan Schollenberger  2 , Lei Zheng  2 , Clifton O Bingham  1 , Ami A Shah #  1 , Laura C Cappelli #  3
Affiliations
Observational Study

Immune checkpoint inhibitor-induced inflammatory arthritis persists after immunotherapy cessation

Tawnie J Braaten et al. Ann Rheum Dis. 2020 Mar.

Abstract

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.

Keywords: Arthritis; Autoimmune Diseases; Inflammation; Synovitis.

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Conflict of interest statement

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.

Figures

Figure 1
Figure 1
Kaplan-Meier curves for persistent arthritis based on immunotherapy regimen, irAEs, and tumour response. (A) demonstrates increased arthritis persistence in those treated with combination ICI therapy. (B) shows more persistent arthritis in those with >2 additional irAEs. (C) shows that patients with a tumour response of complete response or partial response (CR/PR) had more persistent arthritis compared with those with stable disease or progressive disease (SD/PD) at follow-up. IA, inflammatory arthritis; ICI, immune checkpoint inhibitor; irAEs, immune-related adverse events.
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