Clinical presentation of immune checkpoint inhibitor-induced inflammatory arthritis differs by immunotherapy regimen

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Abstract

Introduction: Immune checkpoint inhibitors (ICIs) are a class of cancer immunotherapy, increasingly utilized to treat malignancies. Inflammatory arthritis (IA) is a potential consequence of ICI use, but there is limited information to guide evaluation and management of this immune-related adverse event (irAE). This study aimed to characterize clinical phenotypes, IA treatment and response in the largest cohort of patients with ICI-induced IA reported to date. Methods: Patients with rheumatologist-confirmed IA occurring during or after ICI treatment with no prior history of autoimmune disease were included. Data were analyzed by ICI treatment regimen; treatments included combination CTLA-4/PD-1 inhibition, anti-PD-1 or anti-PD-L1 monotherapy. Relationship to the development of other irAEs, management of IA, and outcomes of IA management were evaluated. Results: Of 30 patients identified, those treated with combination ICI therapy were more likely to present with knee arthritis, to have higher levels of C-reactive protein, to have already had another irAE, and to have a reactive arthritis-like phenotype. In contrast, patients treated with ICI monotherapy were more likely to have initial small joint involvement and to have IA as their only irAE. Ten patients required additional immunosuppression beyond corticosteroids, with TNF-inhibitors and/or methotrexate. Tumor progression while on non-corticosteroid immunosuppression was not seen in those with initial tumor response to ICIs. Conclusion: These data suggest that distinct IA phenotypes may emerge with exposure to different ICI regimens. The majority of patients referred to rheumatology required systemic immunosuppression to manage their IA symptoms. Tumor progression was not seen in patients requiring TNF-inhibitors.

Original languageEnglish (US)
JournalSeminars in Arthritis and Rheumatism
DOIs
StateAccepted/In press - Jan 1 2018

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Immunotherapy
Arthritis
Immunosuppression
Neoplasms
Phenotype
Therapeutics
Reactive Arthritis
Rheumatology
Methotrexate
C-Reactive Protein
Autoimmune Diseases
Knee
Adrenal Cortex Hormones
Joints

Keywords

  • Cancer
  • Immune checkpoint inhibitor
  • Immunotherapy
  • Inflammatory arthritis

ASJC Scopus subject areas

  • Rheumatology
  • Anesthesiology and Pain Medicine

Cite this

@article{87cf9856c1494366b46b460dfca9036d,
title = "Clinical presentation of immune checkpoint inhibitor-induced inflammatory arthritis differs by immunotherapy regimen",
abstract = "Introduction: Immune checkpoint inhibitors (ICIs) are a class of cancer immunotherapy, increasingly utilized to treat malignancies. Inflammatory arthritis (IA) is a potential consequence of ICI use, but there is limited information to guide evaluation and management of this immune-related adverse event (irAE). This study aimed to characterize clinical phenotypes, IA treatment and response in the largest cohort of patients with ICI-induced IA reported to date. Methods: Patients with rheumatologist-confirmed IA occurring during or after ICI treatment with no prior history of autoimmune disease were included. Data were analyzed by ICI treatment regimen; treatments included combination CTLA-4/PD-1 inhibition, anti-PD-1 or anti-PD-L1 monotherapy. Relationship to the development of other irAEs, management of IA, and outcomes of IA management were evaluated. Results: Of 30 patients identified, those treated with combination ICI therapy were more likely to present with knee arthritis, to have higher levels of C-reactive protein, to have already had another irAE, and to have a reactive arthritis-like phenotype. In contrast, patients treated with ICI monotherapy were more likely to have initial small joint involvement and to have IA as their only irAE. Ten patients required additional immunosuppression beyond corticosteroids, with TNF-inhibitors and/or methotrexate. Tumor progression while on non-corticosteroid immunosuppression was not seen in those with initial tumor response to ICIs. Conclusion: These data suggest that distinct IA phenotypes may emerge with exposure to different ICI regimens. The majority of patients referred to rheumatology required systemic immunosuppression to manage their IA symptoms. Tumor progression was not seen in patients requiring TNF-inhibitors.",
keywords = "Cancer, Immune checkpoint inhibitor, Immunotherapy, Inflammatory arthritis",
author = "Laura Cappelli and Julie Brahmer and Patrick Forde and Dung Le and Evan Lipson and Jarushka Naidoo and Lei Zheng and Clifton Bingham and Ami Shah",
year = "2018",
month = "1",
day = "1",
doi = "10.1016/j.semarthrit.2018.02.011",
language = "English (US)",
journal = "Seminars in Arthritis and Rheumatism",
issn = "0049-0172",
publisher = "W.B. Saunders Ltd",

}

TY - JOUR

T1 - Clinical presentation of immune checkpoint inhibitor-induced inflammatory arthritis differs by immunotherapy regimen

AU - Cappelli, Laura

AU - Brahmer, Julie

AU - Forde, Patrick

AU - Le, Dung

AU - Lipson, Evan

AU - Naidoo, Jarushka

AU - Zheng, Lei

AU - Bingham, Clifton

AU - Shah, Ami

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Introduction: Immune checkpoint inhibitors (ICIs) are a class of cancer immunotherapy, increasingly utilized to treat malignancies. Inflammatory arthritis (IA) is a potential consequence of ICI use, but there is limited information to guide evaluation and management of this immune-related adverse event (irAE). This study aimed to characterize clinical phenotypes, IA treatment and response in the largest cohort of patients with ICI-induced IA reported to date. Methods: Patients with rheumatologist-confirmed IA occurring during or after ICI treatment with no prior history of autoimmune disease were included. Data were analyzed by ICI treatment regimen; treatments included combination CTLA-4/PD-1 inhibition, anti-PD-1 or anti-PD-L1 monotherapy. Relationship to the development of other irAEs, management of IA, and outcomes of IA management were evaluated. Results: Of 30 patients identified, those treated with combination ICI therapy were more likely to present with knee arthritis, to have higher levels of C-reactive protein, to have already had another irAE, and to have a reactive arthritis-like phenotype. In contrast, patients treated with ICI monotherapy were more likely to have initial small joint involvement and to have IA as their only irAE. Ten patients required additional immunosuppression beyond corticosteroids, with TNF-inhibitors and/or methotrexate. Tumor progression while on non-corticosteroid immunosuppression was not seen in those with initial tumor response to ICIs. Conclusion: These data suggest that distinct IA phenotypes may emerge with exposure to different ICI regimens. The majority of patients referred to rheumatology required systemic immunosuppression to manage their IA symptoms. Tumor progression was not seen in patients requiring TNF-inhibitors.

AB - Introduction: Immune checkpoint inhibitors (ICIs) are a class of cancer immunotherapy, increasingly utilized to treat malignancies. Inflammatory arthritis (IA) is a potential consequence of ICI use, but there is limited information to guide evaluation and management of this immune-related adverse event (irAE). This study aimed to characterize clinical phenotypes, IA treatment and response in the largest cohort of patients with ICI-induced IA reported to date. Methods: Patients with rheumatologist-confirmed IA occurring during or after ICI treatment with no prior history of autoimmune disease were included. Data were analyzed by ICI treatment regimen; treatments included combination CTLA-4/PD-1 inhibition, anti-PD-1 or anti-PD-L1 monotherapy. Relationship to the development of other irAEs, management of IA, and outcomes of IA management were evaluated. Results: Of 30 patients identified, those treated with combination ICI therapy were more likely to present with knee arthritis, to have higher levels of C-reactive protein, to have already had another irAE, and to have a reactive arthritis-like phenotype. In contrast, patients treated with ICI monotherapy were more likely to have initial small joint involvement and to have IA as their only irAE. Ten patients required additional immunosuppression beyond corticosteroids, with TNF-inhibitors and/or methotrexate. Tumor progression while on non-corticosteroid immunosuppression was not seen in those with initial tumor response to ICIs. Conclusion: These data suggest that distinct IA phenotypes may emerge with exposure to different ICI regimens. The majority of patients referred to rheumatology required systemic immunosuppression to manage their IA symptoms. Tumor progression was not seen in patients requiring TNF-inhibitors.

KW - Cancer

KW - Immune checkpoint inhibitor

KW - Immunotherapy

KW - Inflammatory arthritis

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U2 - 10.1016/j.semarthrit.2018.02.011

DO - 10.1016/j.semarthrit.2018.02.011

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JO - Seminars in Arthritis and Rheumatism

JF - Seminars in Arthritis and Rheumatism

SN - 0049-0172

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