Immune checkpoint inhibitor–induced inflammatory arthritis as a model of autoimmune arthritis

Abstract

The development of inflammatory arthritis in patients receiving immune checkpoint inhibitor therapy is increasingly recognized due to the growing use of these drugs for the treatment of cancer. This represents an important opportunity not only to define the mechanisms responsible for the development of this immune‐related adverse event and to ultimately predict or prevent its development, but also to provide a unique window into early events in the development of inflammatory arthritis. Knowledge gained through the study of this patient population, for which the inciting event is known, could shed light into the pathogenesis of autoimmune arthritis. This review will highlight the clinical and immunologic features of these entities to define common elements for future study.

Systemic administration of cytotoxic T lymphocyte‐associated antigen 4 (CTLA‐4)‐Ig abrogates alveolar bone resorption in induced periodontitis through inhibition of osteoclast differentiation and activation: An experimental investigation

“…Alternatively, CTLA‐4‐Ig could have exerted a direct effect on osteoclast precursors, via binding to the CD80/CD86 on the surface of monocytes/macrophages 3 , 34–36 . In order to further investigate the mechanisms that may account for the effect of CTLA‐4‐Ig on bone, a series of in vitro experiments were conducted.…”

A20: a master regulator of arthritis

“…It is likely that high levels of TNF-α, secreted by macrophages, induce Th1-mediated inflammation [ 109 ]. This is a key cascade in the development of rheumatoid arthritis, causing classic features such as consequent synovial inflammation and joint destruction [ 110 ].…”

Clonally expanded CD38hi cytotoxic CD8 T cells define the T cell infiltrate in checkpoint inhibitor-associated arthritis

“…Blocking immune checkpoint pathways such as PD-1/PD-L1 releases T cells from negative regulation and can induce potent anti-tumor responses (1) . However, ICI therapy can also activate immune reactions against healthy tissues, leading to immune related adverse events (irAEs) in >80% of patients (1)(2)(3)(4)(5)(6)(7)(8) . These irAEs permit the study of human autoimmune responses from the unprecedented perspective of a defined inciting event-administration of ICI therapy.…”

“…Here we focus on the inflammatory arthritis that develops following anti-PD-1/PD-L1 and anti-CTLA-4 therapies. This ICI-associated arthritis (ICI-arthritis) occurs in ~5% of treated patients and often clinically resembles classic inflammatory arthritides, such as rheumatoid arthritis (RA) and psoriatic arthritis (PsA), causing pain, swelling, and inflammatory joint effusions in both small and large joints (1,(3)(4)(5)(6)(7) . ICI-arthritis can present within weeks-to-months after adminstering ICI therapy, but unlike most irAEs, can last years after therapy discontinuation.…”