POS1101 IL5 MODULATION AND THROMBOTIC RISK IN PATIENTS WITH EOSINOPHILIC GRANULOMATOSIS WITH POLYANGIITIS: A PROOF-OF-CONCEPT MONOCENTRIC STUDY
Authors: G. A. Ramirez, A. Cariddi, M. Lanzillotta, G. Benanti, V. Batani, L. Moroni, M. Matucci-Cerinic, L. Dagna
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Eosinophilic granulomatosis with polyangiitis (EGPA) is a systemic autoimmune disease characterised by eosinophilia and small-vessel inflammation. Thromboembolism is a relatively common complication of small-vessel vasculitides, including EGPA. Eosinophils are endowed with a significant thrombogenic potential, possibly due to their ability to cause endothelial damage and activate the coagulation cascade by expressing tissue factor. Modulation of interleukin 5 (IL5) is effective in controlling systemic eosinophilic inflammation. Little is known about the potential impact of anti-IL5 agents on thromboembolism. <h3>Objectives:</h3> To assess whether treatment with mepolizumab (MPZ, an anti-IL5 monoclonal antibody) affects thromboembolism rates in patients with EGPA. <h3>Methods:</h3> We retrospectively reviewed the clinical and treatment history of 81 consecutive patients with EGPA. We investigated whether patients had experienced one or more thrombotic events, and gathered details about the timing and type of the first event. We also recorded whether patients did or did not receive MPZ and the timeframe of exposure to the drug. Patients exposed to MPZ were analysed before and during MPZ treatment. Disease activity and chronic damage were assessed with the Birmingham vasculitis activity score (BVAS) version 3 and the Vasculitis Damage Index (VDI), respectively. Data are expressed as median (interquartile range) unless otherwise specified. <h3>Results:</h3> Of 81 patients with EGPA, 57 were and 24 were not exposed to MPZ. Exposure to MPZ started after 61 (29-150) months from disease onset and was observed for 45 (14-48) months. Eighteen patients experienced 21 thrombotic events. The most frequent were deep vein thrombosis (n=7), followed by myocardial infarction (n=4), endocardial thrombosis (n=4), retinal thrombosis (n=3) and stroke (n=3). Six events (33%) occurred at disease onset, while the remainder occurred after 46 (12-133) months. Thrombotic event incidence rates were 1.1/100 person-years (95%CI=0.1-4.0) in-MPZ and 2.6/100 person-years (95%CI=1.5-4.3) off-MPZ. By excluding pre-exposure observations, patients never exposed to MPZ had a higher rate of thrombotic events (n=9/24) compared to patients receiving MPZ (n=2/57; HR=6.7, 95%CI=1.4-33.3, p=0.018). When pre-exposure records were combined with non-exposures, a similar trend was still observed (HR=4.2, 95%CI= 0.9-20; p=0.062). Compared to patients without thrombosis, patients with thrombosis had higher BVAS scores at EGPA onset [12 (10-14) vs 8 (6-13); p=0.042] and a higher frequency of heart involvement (63% vs 12%; p&lt;0.001). No other associations were found with distinct organ involvement or damage accrual. <h3>Conclusion:</h3> Treatment with MPZ was associated with a low frequency of thrombotic events, consistent with clinical trials and real-life studies [1-3]. Dampening eosinophilic inflammation through MPZ might contribute to reduce the risk of thrombotic events in patients with EGPA [4], especially at later disease stages. Further studies are needed to validate these findings and obtain insights on potential mechanistic implications of IL5 modulation towards haemostasis. <h3>REFERENCES:</h3> [1] Wechsler ME, et al., N Engl J Med. 2017. [2] Bettiol A, et al., Arthritis Rheumatol. 2022. [3] Ishii T, et al., Mod Rheumatol. 2023. [4] Bettiol A, et al., Eur Respir J. 2021. <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>