Rheumatic Manifestations in Patients Treated with Immune Checkpoint Inhibitors

Abstract

Immune checkpoint inhibitors (ICIs) are monoclonal antibodies that activate the immune system, aiming at enhancing antitumor immunity. Their clinical efficacy is well-documented, but the side effects associated with their use are still under investigation. These drugs cause several immune-related adverse events (ir-AEs), some of which stand within the field of rheumatology. Herein, we present a literature review performed in an effort to evaluate all publicly available clinical data regarding rheumatic manifestations associated with ICIs. The most common musculoskeletal ir-AEs are inflammatory arthritis, polymyalgia rheumatica and myositis. Non-musculoskeletal rheumatic manifestations are less frequent, with the most prominent being sicca, vasculitides and sarcoidosis. Cases of systemic lupus erythematosus or scleroderma are extremely rare. The majority of musculoskeletal ir-AEs are of mild/moderate severity and can be managed with steroids with no need for ICI discontinuation. In severe cases, more intense immunosuppressive therapy and permanent ICI discontinuation may be employed. Oncologists should periodically screen patients receiving ICIs for new-onset inflammatory musculoskeletal complaints and seek a rheumatology consultation in cases of persisting symptoms.

Immune Checkpoint Inhibitor-Associated Scleroderma-Like Syndrome: A Report of a Pembrolizumab-Induced “Eosinophilic Fasciitis-Like” Case and a Review of the Literature

“…Rheumatologic irAEs are common and well described in the current literature. While arthralgia, myalgia, arthritis and myositis are some of the most common musculoskeletal rheumatic manifestations, scleroderma and scleroderma-like cases related to CPIs are only rarely described among the non-musculoskeletal rheumatic irAEs [2][3][4][5][6][7][8].…”

Activation of T cell checkpoint pathways during β-cell antigen presentation by engineered dendritic cells promotes protection of non-obese diabetic mice from type 1 diabetes

“…However, while largely effective in cancers, these therapies also produced autoimmune etiology in patients [34][35][36][37] further substantiating their role in maintaining peripheral self-antigen tolerance.…”

Organ-specific Adverse Events of Immune Checkpoint Inhibitor Therapy, with Special Reference to Endocrinopathies

“…Various rheumatological manifestations are encountered in up to 7% of patients treated with ICIs, ranging from arthralgias, myalgias, inflammatory arthritis and polymyalgia rheumatica, to polymyositis and sicca manifestations. 36,37 These features usually indicate better therapeutic response to ICIs. For grade ≥2 adverse events, including inflammatory arthritis, a referral to a rheumatologist and therapy with a tapering course of corticosteroids are necessary.…”