Rheumatic immune-related adverse events of checkpoint therapy for cancer: case series of a new nosological entity

Abstract

Immunotherapy of cancer with checkpoint inhibitors has been associated with a spectrum of autoimmune and systemic inflammatory reactions known as immune-related adverse events (irAEs). Rheumatic irAEs are infrequently reported and extensively described. Here, we report our experience over an 18-month period with 15 patients evaluated in the rheumatology department for rheumatic irAEs. We identified 13 patients without pre-existing autoimmune disease (AID) who subsequently developed rheumatic irAEs, and two with established AID referred pre-emptively. irAEs encountered included: inflammatory arthritis, sicca syndrome, polymyalgia rheumatica-like symptoms and myositis. All cases required glucocorticoids, and three required a biological agent. Rheumatic irAEs led to temporary or permanent cessation of immunotherapy in all but five patients. One patient with pre-existing AID experienced a flare after starting immunotherapy. Our findings underscore that rheumatic irAEs are complex, at times require additional immunosuppressive therapy, and may influence ongoing immunotherapy regimens for the primary disease. Similar irAEs will be increasingly seen as checkpoint inhibitors adopted as standard of care in the community.

Rheumatic Syndromes Associated With Immune Checkpoint Inhibitors: A Single‐Center Cohort of Sixty‐One Patients

“…Methotrexate and hydroxychloroquine were the most commonly utilized DMARDs in our cohort, with tumor necrosis factor inhibitors (TNFi) commonly used in several other reported studies . While immunosuppression may be necessary in some patients, there is concern with regard to dampening the host antitumor response.…”

Do current approaches to assessing therapy related adverse events align with the needs of long-term cancer patients and survivors?

“…Thus, the version of CTCAE (or other ontology) can have a significant impact on the nature, naming, and overall reported incidence of AEs used in cost evaluation studies. Several clinical specialty areas that address common antineoplastic treatment-related AEs (e.g., rheumatology) have developed their own AE ontologies and grades to reflect the more nuanced perspective of a specialist [130]. Experts have noted that the recording of AEs by non-specialists can result in non-specific calls such as 'cardiac-general' with no detail about the nature of the cardiotoxicity [127].…”

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

“…ICI‐IA is clinically heterogeneous with some features similar to RA and others reminiscent of SpA . Understanding how clinical features and response to treatment of ICI‐IA compare to those of known autoimmune diseases can potentially inform our models of pathogenesis for all the disease entities.…”

“…Thus far, most reports are from small case series or single‐center cohort studies and the assays used to detect seropositivity are not uniform between studies. Despite these limitations, aggregation of the data from multiple studies reveals a low rate of seropositivity among patients developing IA following treatment with ICI therapy with 5.5% (12/217; range 0%‐36%) positive for RF and 5% (11/217; range 0%‐11%) positive for ACPAs . In a study comparing ICI‐IA patients to ethnically matched counterparts with RA, 7.7% of ICI‐IA patients were positive for RF or ACPAs, whereas 64.6% of RA patients were positive for ACPAs and 56.7% positive for RF, with 49.3% being positive for both .…”