POS0615 CLINICAL AND GENETIC FACTORS ASSOCIATED WITH RHEUMATOLOGIC IMMUNE-RELATED ADVERSE EVENTS IN PATIENTS RECEIVING IMMUNE CHECKPOINT INHIBITORS: A BICENTRIC CASE-CONTROL STUDY

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Background: Due to their mechanisms of action, immune checkpoint inhibitors (ICI) can cause immune-related adverse events (irAE), including a range of rheumatologic manifestations. The risk factors for developing rheumatologic irAEs are not clearly established possibly reflecting the diversity of irAEs, underlying cancers, and mechanisms of action of ICIs. Objectives: The objective of this study was to identify clinical, biological, and genetic factors associated with the occurrence of rheumatologic irAEs. Methods: This case-control study was conducted in two university hospitals in Île-de-France. A total of 77 patients were included. The 31 cases were identified between February 2016 and April 2024 in dermatology, pulmonology, and oncology departments and then validated by a rheumatologist (CB, EE). The 46 controls were consecutively included and matched to the cases based on cancer type and follow-up department. Controls had received at least one year of treatment with ICIs without developing rheumatologic irAEs. Clinical and biological characteristics were compared between cases and controls (χ² test, Fisher's exact test, or Mann-Whitney test, as appropriate). Associations between patient variables and the occurrence of irAEs were tested using logistic regression. Time to rheumatologic irAEs was compared between male and female patients with log-rank test. Results: Among the 31 cases (16 women, 15 men), the following rheumatologic irAEs were identified: 15 polymyalgia rheumatica-like, 4 rheumatoid arthritis-like, 4 spondyloarthritis-like, 5 myositis-like, and 3 unclassified arthritides. IrAEs occurred at a median of 8 weeks after starting ICIs. During treatment, an irAE was more frequently observed in women vs men (p = 0.008) (Figure 1). Logistic regression revealed an independent association between the occurrence of irAEs and female gender (OR = 3.55, IC95%: 1.65-7.6, p=0.001) and anti-PD-L1 treatment (OR = 7.23, IC95%: 2.30-22.7, p < 0.001). Combined anti-PD-1 and anti-CTLA-4 checkpoint blockade, ICI + chemotherapy, and age were not significantly associated with irAEs (Figure 2). Subgroup analyses in women showed an independent association of irAEs with anti-PD-L1 treatment (OR = 17.82, IC95%: 2.18-145, p=0.007) and age > 65 years (OR = 4.29, IC95%:1.13-16, p=0.033). All cases for which HLA typing (class I and/or class II) was available (n = 12) had haplotypes associated with predisposition to the specific rheumatologic condition observed. Conclusion: Female gender, anti-PD-L1 treatment and age > 65 years in women are independently associated with the occurrence of rheumatologic irAEs. Additionally, cases had HLA genetic backgrounds predisposing to the type of rheumatologic manifestation observed during ICI treatment. Figure 1Time to a rheumatologic immune-related adverse event in female vs male patients (log-rank test). Figure 2Factors associated with the development of rheumatologic irAEs (logistic regression). ICI: immune-checkpoint inhibitor. REFERENCES: NIL . Acknowledgements: NIL . Disclosure of Interests: None declared . © The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.

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