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.