AB0216 IMMUNE-RELATED ARTHRITIS: IMPACT OF DMARDs

Background: Immunocheckpoint inhibitors (ICIs) revolutionized cancer therapy due to their efficacy on long-term survival. The most employed drugs are directed against CTLA-4 and PD1/PDL-1, whose main role is to stimulate immune system and enhance antitumour response, regulating T-cellular response1. However, this uncontrolled and non-selective immune response may lead to different immune-related adverse events (irAEs) 2. Rheumatic toxicity has an overall incidence of about 10%. The most frequent manifestation is the joint involvement (5-7%), including inflammatory arthralgia, arthritis, polymyalgia rheumatica (PMR)-like syndrome (ir-arthritis phenotype). Glucocorticoids (GCs) represent the first line therapy; conventional and biologic disease modifying anti-rheumatic drugs (cs- and bDMARDs) are employed in most severe cases to reduce GCs but the impact on oncological outcome is debated 3,4. Objectives: to describe a monocentric cohort of oncologic patients (pts) with ir-arthritis phenotype toxicity and to analyse the role of an early use of cs- and bDMARDs on oncological outcome. Methods: retrospective analysis of oncologic pts with ir-arthritis phenotype followed from January 2019 to November 2023. Pts with a pre-existing rheumatic disease (pRD) were included. The severity of irAEs was established according to the Common Terminology Criteria for Adverse Events (CTCAE). The chi-square/Fisher's test and the t-test were applied to evaluate association between different variables (age, cancer type, first line ICI, pRD, therapies) and oncological outcome in terms of progression or not. The Charlson index (CCI) was used to assess the influence of comorbidities on the overall outcome. Results: 31 pts (21 males) with a mean age of 69.5y were included. The most frequent neoplasms were non-small cell lung cancer (35%) and melanoma (19%). The most employed drugs were anti-PD1. Five pts had a pRD (3 PMR, 1 rheumatoid arthritis and 1 psoriatic arthritis) and were treated with methotrexate (MTX) or hydroxychloroquine (HCQ) at the beginning of ICI. The mean (±standard deviation, SD) time to irAEs onset was 17 weeks (±23) with severity grade G2/G3 in the large majority (90%) and with a median follow-up of 15 months (IQR: 5-23). Twelve pts developed PMR-like syndrome, 12 arthritis, 7 inflammatory arthralgia. All pts with pRD relapsed. All pts started GCs (mean initial dose PN-eq 30 mg and mean cumulative dose PN-eq 1.3 g), in 20 pts ICI was transiently interrupted. Due to recurrence of irAEs during two-month GC tapering, a csDMARD or an IL6 inhibitor was started in 15 and 5 pts, respectively (Table 1). During the follow-up, 14 pts had an oncological progression and/or died, while 17 had a stable disease or a partial/complete response. An association between csDMARD use and no cancer progression was noted (p= 0.045) (Table 2). At last follow-up, all pts were recovered from irAEs. Conclusion: In our cohort, an early introduction of DMARDs showed to be effective in counteracting irAEs, sparing GC, without negatively affecting the oncological outcome. REFERENCES: 1 Weinmann, S. C. & Pisetsky, D. S. Mechanisms of immune-related adverse events during the treatment of cancer with immune checkpoint inhibitors. Rheumatol. Oxf. Engl.58, vii59–vii67 (2019). 2 Shen, P. et al. Rheumatic Manifestations and Diseases From Immune Checkpoint Inhibitors in Cancer Immunotherapy. Front. Med.8, 762247 (2021). 3 Reid, P. & Cappelli, L. C. Treatment of rheumatic adverse events of cancer immunotherapy. Best Pract. Res. Clin. Rheumatol.36, 101805 (2022). 4 Kostine, M. et al. EULAR points to consider for the diagnosis and management of rheumatic immune-related adverse events due to cancer immunotherapy with checkpoint inhibitors. Ann. Rheum. Dis.80, 36–48 (2021). Acknowledgements: NIL. Disclosure of Interests: None declared.