Rheumatic complications of checkpoint inhibitors: Lessons from autoimmunity

Abstract

Immune checkpoint inhibitors are now an established treatment in the management of a range of cancers. Their success means that their use is likely to increase in future in terms of the numbers of patients treated, the indications and the range of immune checkpoints targeted. They function by counteracting immune evasion by the tumor but, as a consequence, can breach self-tolerance at other sites leading to a range of immune-related adverse events. Included among these complications are a range of rheumatologic complications, including inflammatory arthritis and keratoconjunctivitis sicca. These superficially resemble immune-mediated rheumatic diseases (IMRDs) such as rheumatoid arthritis and Sjogren's disease but preliminary studies suggest they are clinically and immunologically distinct entities. However, there appear to be common processes that predispose to the development of both that may inform preventative interventions and predictive tools. Both groups of conditions highlight the centrality of immune checkpoints in controlling tolerance and how it can be restored. Here we will discuss some of these commonalities and differences between rheumatic irAEs and IMRDs.

Keywords: CTLA4; PD1; arthritis; autoimmunity; checkpoint inhibitors; immunotherapy; rheumatology.

FIGURE 1

Common mechanisms underlying rheumatic irAEs and IMRDs. Multiple factors that are known to contribute to the development of common IMRDs have been shown to predispose to the development of rheumatic irAEs, including genetic and environmental factors. Similarly there are shared alterations in peripheral immunity that herald the development of both.