Immune checkpoint inhibitor-induced inflammatory arthritis persists after immunotherapy cessation

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
JournalAnnals of the rheumatic diseases
DOIs
StateAccepted/In press - Jan 1 2019

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Immunotherapy
Arthritis
Tumors
Immunosuppressive Agents
Logistics
Hazards
Neoplasms
Rheumatology
Therapeutics
Disease Management
Proportional Hazards Models
Immunosuppression
Observational Studies
Logistic Models
Outcome Assessment (Health Care)
Prospective Studies

Keywords

  • Arthritis
  • Autoimmune Diseases
  • Inflammation
  • Synovitis

ASJC Scopus subject areas

  • Rheumatology
  • Immunology and Allergy
  • Immunology
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

@article{0025d8b374df495c9bfdddf29324f16a,
title = "Immune checkpoint inhibitor-induced inflammatory arthritis persists after immunotherapy cessation",
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",
author = "Braaten, {Tawnie J.} and Julie Brahmer and Patrick Forde and Dung Le and Evan Lipson and Jarushka Naidoo and Megan Schollenberger and Lei Zheng and Clifton Bingham and Ami Shah and Laura Cappelli",
year = "2019",
month = "1",
day = "1",
doi = "10.1136/annrheumdis-2019-216109",
language = "English (US)",
journal = "Annals of the Rheumatic Diseases",
issn = "0003-4967",
publisher = "BMJ Publishing Group",

}

TY - JOUR

T1 - Immune checkpoint inhibitor-induced inflammatory arthritis persists after immunotherapy cessation

AU - Braaten, Tawnie J.

AU - Brahmer, Julie

AU - Forde, Patrick

AU - Le, Dung

AU - Lipson, Evan

AU - Naidoo, Jarushka

AU - Schollenberger, Megan

AU - Zheng, Lei

AU - Bingham, Clifton

AU - Shah, Ami

AU - Cappelli, Laura

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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.

AB - 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.

KW - Arthritis

KW - Autoimmune Diseases

KW - Inflammation

KW - Synovitis

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U2 - 10.1136/annrheumdis-2019-216109

DO - 10.1136/annrheumdis-2019-216109

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JO - Annals of the Rheumatic Diseases

JF - Annals of the Rheumatic Diseases

SN - 0003-4967

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