Risk of Toxicity After Initiating Immune Checkpoint Inhibitor Treatment in Patients With Rheumatoid Arthritis

Abstract

Introduction: Immune checkpoint inhibitors (ICIs) are increasingly used to treat advanced cancer. Rheumatoid arthritis (RA) is associated with an increased risk of malignancies; however, patients with RA have been excluded from ICI trials. In this study, we evaluated risk of toxicity after initiation of ICI treatment in RA patients. Methods:We conducted a single-institution, medical records review analysis to assess the incidence of immune-related adverse events (irAEs) and autoimmune disease (AID) flares among patients with AIDs treated with ICIs from 2011 to 2018. A subgroup analysis for RA patients was performed with frequencies of irAEs and AID flares reported.Results: Twenty-two patients with RA who were treated with ICI for malignancy were identified. At the time of ICI initiation, 86% had inactive RA disease activity. Immune-related adverse events occurred in 7 (32%) of patients, with 2 (9%) developing grade 3 (i.e., severe) irAEs. Immune checkpoint inhibitors were temporarily discontinued because of irAEs in 5 patients (23%), and permanently in 1 patient. Rheumatoid arthritis flares occurred in 12 patients (55%). Of those, 10 (83%) received oral corticosteroids with an adequate treatment response.Conclusions: Our analysis suggests that irAEs following ICI treatment are not increased among RA patients compared with other cancer patients. Heightened RA disease activity during ICI treatment is common, but most adverse events are manageable with oral corticosteroids, and few require permanent ICI discontinuation. A close collaboration between the oncologist and rheumatologist is advisable when considering ICIs in patients with RA.

Factors Influencing the Adjuvant Therapy Decision: Results of a Real-World Multicenter Data Analysis of 904 Melanoma Patients

“…A close interdisciplinary collaboration for managing ICI toxicity is recommended [ 59 ]. Patients need to be informed that even quiescent rheumatoid arthritis can flare during ICI treatment [ 60 ], and that symptoms may persist after treatment discontinuation. Increasing experience of ICI use in patients with autoimmune disorders will help to better delineate which patients can safely receive ICI.…”

The Efficacy and Safety of Immune Checkpoint Inhibitors in Patients With Cancer and Preexisting Autoimmune Disease

“…The meta-analysis of Xie et al ( 52 ) reported that the pooled incidence of AID flare and newly developed irAEs were 35% and 33%, respectively, and there was no statistical difference between patients with and without immunosuppressive therapy regarding AID flare. Besides, almost all AID flares occurred at the beginning of ICI therapy—2 weeks to 1 year after initiation, but mostly around 1–2 months ( 15 , 27 , 29 , 31 , 33 , 41 ). Most AID flares had similar manifestations and affected the same anatomic sites as prior AID symptoms ( 27 , 31 , 36 ).…”

Immunotherapy to treat malignancy in patients with pre-existing autoimmunity

“…The authors found that while most patients were clinically quiescent prior to initiating immunotherapy for malignant conditions, at least 50% of patients flared, which seems to support data from other series. 64 Overall, these findings suggest that ICIs lead to similar rates of irAEs in patients with pre-existing AIDs compared with those without existing AID and are summarized in table 1.…”