Rheumatic immune-related adverse events induced by immune checkpoint inhibitors

Abstract

Immune checkpoint inhibitors (ICIs) block the major inhibitory pathways in T cells, resulting in an augmented antitumor response. Immune-related adverse events (irAEs) are a new class of side effects caused by ICIs and tend to be more prevalent in patients with preexisting autoantibodies and autoimmune diseases. The rheumatic subset of irAEs mainly includes arthralgia, arthritis, myalgia, myositis, vasculitis, sicca syndrome, scleroderma and systemic lupus erythematosus. The most common classification system for AEs, the Common Terminology Criteria for Adverse Events, is of limited use for irAEs, especially rheumatic irAEs. Therapy with glucocorticoid and temporary or permanent discontinuation of ICIs are the cornerstones of irAE treatment, and can be complemented with immunosuppressants (e.g., methotrexate), biologic agents (e.g., tumor necrosis factor inhibitors and interleukin-6 receptor antagonists), intravenous immunoglobin and plasma exchange. Thus, the evaluation and treatment of rheumatic irAEs require multidisciplinary cooperation among physicians. Here, we review the most prevalent ICI-associated rheumatic irAEs.

Keywords: CTLA-4 inhibitors; PD-1 inhibitors; PD-L1 inhibitors; immune checkpoint inhibitors; rheumatic immune-related adverse events.