Immune checkpoint inhibitor-induced inflammatory arthritis: identification and management

ABSTRACT

Introduction

Immune checkpoint inhibitors (ICIs) have proved to be groundbreaking in the field of oncology. However, immune system overactivation from ICIs has introduced a novel medical entity known as immune-related adverse events (irAEs), that can affect any organ or tissue. ICI-induced inflammatory arthritis (ICI-IIA) is the most common musculoskeletal irAE and can lead to significant morbidity and limitation in anti-cancer therapy.

Areas covered

In this review, the authors focus on ICI-IIA. Relevant articles were identified through PubMed searches, spanning 2010 to the present. The authors detail the current understanding of its pathogenesis, diagnostic evaluation, and management strategies.

Expert opinion

ICI-IIA is a complex irAE that we are just beginning to understand mechanistically and pathologically. It often presents later in the disease course than other irAEs and, due to various reasons, is under-recognized. In some patients, ICI-IIA may become a chronic disease, which distinguishes it from most irAEs that resolve after ICI discontinuation. Multiple important questions still demand further research including which patients may develop ICI-IIA? What are possible diagnostic and prognostic markers? Do anti-arthritis therapies interfere with the anti-tumor response? and when should steroid-sparing agents be initiated? Close collaboration and shared decision-making between oncologists, rheumatologists, and the patient are essential when managing this particular irAE.

KEYWORDS:

• Immune checkpoint inhibitors (ICI)
• immune-related adverse events (irAEs)
• immune checkpoint inhibitor-induced inflammatory arthritis (ICI-IIA)
• magnetic resonance imaging (MRI)

Article highlights

• Immune checkpoint inhibitors (ICIs), which have transformed the treatment paradigm of cancer, have been associated with a growing list of immune-related adverse events (irAEs) that may affect almost any organ.

• ICI-induced inflammatory arthritis (ICI-IIA) is the most common musculoskeletal irAE.

• A diagnosis of ICI-IIA is based on clinical signs and symptoms, laboratory work up, and may require advanced imaging or joint fluid aspiration.

• The management of ICI-IIA requires a multidisciplinary approach that takes into account both quality of life and the tension between arthritis elimination and tumor eradication.

• Rheumatologists and oncologists need to work together towards the goal of maximizing anti-tumor effects of the immune system while minimizing irAEs.

Acknowledgments

This research was supported by the Intramural Research Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was funded by the Intramural Research Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health.