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 outcome of 100mg MEPO monthly s/c for a minimum of 36 months. 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 observational study, 20 EGPA patients received anti-IL5 therapy for a minimum of 36M (range 49-68M). All commenced on 100mg s/c MEPO every four weeks. Anti-IL5 therapy switched to BRZ or Res due to partial response or intolerance. Assessment time points included MEPO commencement, 6, 12, 18, 24 and 36 months.

Results: Overall, there was a 50% reduction in steroid usage by 12 months. This continued to reduce to 24M, by which time 2 were off steroids and further 10 on weaning dose ≤ 5mg. Mean steroid dosage continued to decreased to 36 months. The number on adjuvant conventional immunosuppressants (ACIS), reduced over time from 10 at M0 to 4 by 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 49-68M remain on therapy. At 36M, 9 have remained on 100mg s/c MEPO. 10 (50%) have switched to an altenative anti-IL5 agent – 10 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 duration of 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. After 36M, one patient required cyclophosphamide along with anti-IL5 therapy for myocarditis. A further patient had Rituximab for EGPA/ Rheumatoid arthritis overlap between anti-IL5 agents.

Conclusion: In this study, there was a 50% reduction in steroid dosage by 12 months and steroid requirements continue to decrease to 36M. 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. The relapsing nature of EGPA places a dependency of therapy on steroids and this study demonstrated sustained and ongoing improvement annually with continued anti-IL5 therapy. Some participants required a switch in anti-IL5 agent.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/investigating-the-impact-of-anti-il5-therapy-in-the-management-of-relapsing-and-refractory-eosinophilic-granulomatosis-with-polyangiitis-egpa-a-three-year-longitudinal-perspective-and-beyond/