Flare incidences of pre-existing rheumatologic diseases in patients with solid tumors receiving immune checkpoint inhibitors: A systematic review and meta-analysis.

OBJECTIVES Immune checkpoint inhibitors (ICIs) are increasingly used in oncology, but concerns persist regarding flare risks of pre-existing rheumatologic diseases in patients receiving ICIs. This meta-analysis study aims to evaluate the incidence and severity of rheumatologic disease flares in patients with solid tumors treated with ICIs.

METHODS We searched PubMed and Embase through May 2024 to identify studies reporting the incidences of pre-existing rheumatologic disease flare due to ICIs for their cancer. A random-effects proportional meta-analysis was conducted to pool the incidence of grade 1-5 and grade 3-5 flares, stratified by rheumatologic disease types and ICI subtypes.

RESULTS In total, 31 studies comprising more than 700 patients were identified for meta-analyses. The pooled incidence of grade 1-5 flare was 33.8% (95% confidence interval [CI]: 25.8-42.2%), with a median onset of 38.5 days (IQR: 30.0-52.6) after ICI initiation. Grade 3-5 flare incidence rate was 4.2% (95% CI: 0.6-9.6). Flare incidences varied among rheumatologic diseases: 40.9% in rheumatoid arthritis, 46.4% in psoriatic arthritis, 11.3% in systemic sclerosis, and 3.8% in systemic lupus erythematosus, respectively. For disease flares, 83% (n = 134/161) received systemic corticosteroids, and 81% (n = 30/37) of such cases had clinical improvement. ICIs were permanently discontinued in 17% of flare cases.

CONCLUSIONS Incidences of rheumatologic disease flare from ICIs vary depending on the underlying rheumatologic condition. This underscores the need for close communication between rheumatologists and oncologists to assess risk of flares prior to ICI initiation and manage both rheumatologic disease and cancer after the incidences of disease flares.