345. Longitudinal impact (≥ 24months) of Anti-IL5 therapy in Eosinophilic Granulomatosis with Polyangiitis (EGPA)

Background/ Purpose: In the randomized, placebo-controlled MIRRA trial for relapsing and refractory eosinophilic granulomatosis with polyangiitis (EGPA), adjuvant therapy with 300mg anti-IL5 mAB Mepolizumab [MEPO] for 12 months (M), accrued longer times in remission, reduced steroid exposure and reduced relapse rates2. The aim of this study is to analyze the longer term outcomes of 100mg MEPO monthly s/c for a minimum of 24M. Changes to adjuvant immunosuppression and indications for anti-IL5 class switch from MEPO 100mg s/c to Benralizumab (BRZ) or Reslizumab (Res) were assessed. Methods: In this retrospective descriptive study, 20 EGPA patients received 100mg s/c MEPO every 4 weeks for a minimum of 24M (range 24-43M). Anti-IL5 therapy switched between agents for poor response or intolerance. Time points of assessment included MEPO commencement, 6, 12, 18 and 24 months. Results: Overall, there was a 50% reduction in steroid usage by 12 months. This continued to reduce to 24M, by which time 2 had withawn steroids and 10 were on weaning dose ≤ 5mg.The number on adjuvant conventional immunosuppressants (ACIS), reduced over time from 10 at M0 to 4 at M24. Clinical benefits included ANCA serology normalized in all four positive patients by 12 months. Mean eosinophil count reduced from 0.42mg ±0.33 X109/L at M0 to 0.04±0.03 X109/L at 12 and 24M. BVAS reduced from median 5 [3-7], to 0 [0-1] by 24M. The change in mean FEV1 over 12 months was from (M0) 2.11±0.66 to (M12) 2.39±0.62 and FVC (M0) 3.42±0.87 to (M12) 3.67±0.93/105.60±20.47 respectively. All 20 EGPA patients receiving anti -IL5 therapy, ranging from 24-43 months remain on therapy. 50% have remained on 100mg s/c MEPO. 10 (50%) have switched to an altenative anti-IL5 agent - 9 switched to benralizumab, 1 initially on benralizumab to reslizumab. 9/10 had achieved partial response prior to switch (reduction in steroids / relapse rate), 1/10 had no response. During the study, 3 patients had a break of therapy, but all resumed anti-IL5 treatment with good response. Hence, all 20 remain on anti-IL5 beyond 24M (range 24 – 43 M). Conclusion: The relapsing nature of EGPA places a dependency of therapy on steroids. In this study, there was a 50% reduction in steroid dosage by 12 months and steroid requirements continue to decrease to 24 M. By 24 months 2 are steroid free and a further 10 on weaning dose ≤ 5mg. Furthermore, the number on adjuvant conventional immunosuppression reduced over the 24M (n=4 at 24M). This study demonstrates that anti-IL5 therapy serves as a favorable model for steroid and conventional immunosuppressant minimization in EGPA. Clinical benefits of reduction in BVAS, improved pulmonary function tests and reduced serum eosinophilia were recorded. Disclosures: David Jayne’s disclosures of commercial conflicts for companies with marketed products for 2021 are: Astra-Zeneca, Aurinia, BMS, Boehringer-Ingelheim, GSK, Janssen, Novartis, Roche/Genentech,Takeda & Vifor