Immune Checkpoint Inhibitor Associated Rheumatic Adverse Events: a Review of Their Presentations and Treatments

Abstract

Immune checkpoint inhibitors (ICI) are now the cornerstone of treatment for metastatic melanoma and are increasingly used in many other advanced stage malignancies. Immune checkpoint inhibitors enhance the endogenous anti-tumor response by inhibiting key regulatory pathways, facilitating robust anti-tumor responses, but often inducing a host of autoimmune toxicities which span multiple organ systems and are referred to as immune-related adverse events (irAEs). Here, we answer common questions rheumatologists may encounter in the management of these patients, including those with pre-existing autoimmune and rheumatic disease. Rheumatic irAEs including inflammatory arthritis, myositis, vasculitis, and sarcoidosis represent unique challenges for oncologists and rheumatologists in both the recognition and management of these entities. There are increasing numbers of case series and retrospective cohort studies describing the clinical and serological presentations and outcomes of patients who have developed rheumatic irAE. While in many ways similar to well established rheumatic diseases, the rheumatic irAE also appear to be different clinically, serologically, and in their response to treatment. There is also a growing body of literature on the use of ICI in patients with pre-existing autoimmune disease. While previously excluded from ICI clinical trials, the current literature would suggest that having a pre-existing autoimmune disease should not be an absolute contraindication to ICI therapy. Prompt diagnosis and treatment initiation is essential to improve patient outcomes and optimize cancer therapy. Guidelines have been developed to guide treating rheumatologists and oncologists; however, important questions remain unanswered with the majority of guidelines based on expert consensus.