Mepolizumab reduced steroid burden for patients with eosinophilic granulomatosis with polyangiitis with and without a vasculitic phenotype

SESSION TITLE: Asthma Biologic Update SESSION TYPE: Rapid Fire Original Inv PRESENTED ON: 10/10/2023 12:00 pm - 12:45 pm PURPOSE: The symptoms and manifestations of eosinophilic granulomatosis with polyangiitis (EGPA) vary and some patients display more pronounced evidence of vasculitis. EGPA treatment relies heavily on both chronic and high-dose oral corticosteroid (OCS) use. The Phase III MIRRA study demonstrated mepolizumab (MEPO), an anti-interleukin-5 monoclonal antibody, reduced relapse rate, increased time in remission, and had an OCS-sparing effect for patients with EGPA. However, the impact of MEPO on EGPA for patients with predominantly vasculitic manifestations is poorly understood. Here, we assessed the OCS-sparing effects of MEPO in patients with and without a vasculitic EGPA phenotype. METHODS: MIRRA was a multicenter, randomized, double-blind, placebo (PBO)-controlled trial in adults with relapsing/refractory EGPA. Patients had ≥4 weeks stable OCS treatment at baseline and received standard of care plus MEPO 300 mg subcutaneous or PBO every 4 weeks for 52 weeks. In this post hoc analysis vasculitic phenotype was defined on 3 markers: antineutrophil cytoplasmic antibody (ANCA) positive test history, baseline Birmingham Vasculitis Activity Score (BVAS) >0, or Vasculitis Damage Index (VDI) score ≥5. The mean (standard deviation [SD]) daily OCS dose and cumulative total OCS exposure (Weeks 0–52) was assessed in the following subgroups: positive ANCA test (no history/history at baseline); baseline BVAS (=0/>0); baseline VDI score (<5/≥5). RESULTS: In total, 68 patients received MEPO and 68 received PBO. In MEPO and PBO arms at baseline, 19% of patients (each arm) had an ANCA-positive history, 54% and 71% had BVAS >0 and 44% and 47% had VDI score ≥5, respectively. Mean (SD) daily OCS dose (mg/day) was lower with MEPO versus PBO in all subgroups: no ANCA-positive history: 9.58 (6.07) versus 13.86 (7.16); ANCA-positive history: 7.72 (6.90) versus 12.16 (9.28); BVAS =0: 7.28 (4.01) versus 14.08 (6.90); BVAS >0: 10.86 (7.27) versus 13.30 (7.87); VDI score <5: 8.69 (5.35) versus 12.78 (6.57); VDI score ≥5: 9.91 (7.23) versus 14.38 (8.57). Reductions in mean cumulative total OCS exposure (mg) over 52 weeks of treatment with MEPO versus PBO were observed in all subgroups: no ANCA-positive history (1552) and ANCA-positive history (878); BVAS =0 (2591) and BVAS >0 (669); VDI score <5 (1677) and VDI score ≥5 (1096). CONCLUSIONS: In patients with relapsing/refractory EGPA, MEPO reduced OCS exposure regardless of vasculitic phenotype. Total reductions in OCS dose were numerically greater in subgroups indicative of less severe vasculitis. CLINICAL IMPLICATIONS: Mepolizumab offers OCS-sparing benefits for patients with EGPA, irrespective of an ANCA-positive test history or the presence of vasculitic features at baseline. Results provide valuable information for clinicians treating patients with EGPA and vasculitis activity or damage. Funding: GSK (115921; NCT02020889) DISCLOSURES: Consultant relationship with Sanofi Please note: 2021-present by Praveen Akuthota, value=consulting fee to university Research funding; advisory boards relationship with GlaxoSmithKline Please note: 2017-present by Praveen Akuthota, value=Grant/Research Support Consulting; Advisory Boards; Research Funding relationship with AstraZeneca Please note: 2017 - present by Praveen Akuthota, value=Grant/Research Support Faculty for sponsored course relationship with AstraZeneca Please note: 2018 - 2020 by Praveen Akuthota, value=Honoraria Consultant relationship with GlaxoSmithKline Please note: 2017-present by Praveen Akuthota, value=Consulting fee Consultant relationship with AstraZeneca Please note: 2017 - present by Praveen Akuthota, value=consulting fee to university Site PI for trials in EGPA and Hypereosinophilic Syndrome relationship with AstraZeneca Please note: 2020-2022 by Praveen Akuthota, value=Grant/Research Support Site PI for Hypereosinophilic Syndrome trial relationship with GlazoSmithKline Please note: 2018-2020 by Praveen Akuthota, value=Grant/Research Support CME speaker relationship with AKH, Inc Please note: 2019-present by Praveen Akuthota, value=Honoraria CME speaker relationship with Projects In Knowledge Please note: 2019-present by Praveen Akuthota, value=Honoraria CME speaker relationship with PRIME Healthcare Please note: 2019-2021 by Praveen Akuthota, value=Honoraria Clinical Trial Site PI relationship with Regeneron Please note: February 2021- by Praveen Akuthota, value=Grant/Research Support Scientific Medical Advisor relationship with Sanofi Please note: 1/1/2022-present by Praveen Akuthota, value=funds to university Site PI relationship with Regeneron Please note: 2021-present by Praveen Akuthota, value=Grant/Research Support Site PI; Scientific Advisor relationship with AstraZeneca Please note: 2018-present by Praveen Akuthota, value=Grant/Research Support Scientific Medical Advisor relationship with GlaxoSmithKline Please note: 2020-present by Praveen Akuthota, value=Consulting fee Employee relationship with GSK Please note: 2016-2023 Added 03/31/2023 by Lee Baylis, source=Web Response, value=Salary Speaker relationship with GSK Please note: 2020-2023 Added 04/01/2023 by BERNHARD HELLMICH, source=Web Response, value=Honoraria No relevant relationships by David Jayne No relevant relationships by Paneez Khoury Employee relationship with GlaxoSmithKline Please note: Sep-2012 to present Added 04/03/2023 by Robert Price, source=Web Response, value=Salary Employee relationship with GlaxoSmithKline Please note: Sep-2012 to present Added 04/03/2023 by Robert Price, source=Web Response, value=Stocks/shares Employee relationship with GSK (GlaxoSmithKline) Please note: $20001 - $100000 by Jared Silver, value=Investments-Stock Employee relationship with GSK (GlaxoSmithKline) Please note: >$100000 by Jared Silver, value=Salary My spouse/partner as a Employee relationship with Change Healthcare Please note: >$100000 by Jared Silver, value=Salary My spouse/partner as a Employee relationship with Change Healthcare Please note: $5001 - $20000 by Jared Silver, value=Investments-Stock No relevant relationships by Benjamin Terrier Consultant relationship with Equillium Please note: N/A Added 03/31/2023 by Michael Wechsler, source=Web Response, value=Consulting fee Consultant relationship with Sentien Please note: N/A Added 03/31/2023 by Michael Wechsler, source=Web Response, value=Consulting fee Consultant relationship with Cohero Health Please note: years by Michael Wechsler, value=Consulting fee Personal fees relationship with Equillium Please note: years by Michael Wechsler, value=Honoraria Personal fees relationship with Genzyme Please note: years by Michael Wechsler, value=Honoraria Personal fees relationship with Boehringer Ingelheim Please note: years by Michael Wechsler, value=Honoraria Personal fees relationship with Regeneron Please note: years by Michael Wechsler, value=Honoraria Personal fees relationship with Sanofi Please note: years by Michael Wechsler, value=Honoraria Personal fees relationship with Novartis Please note: years by Michael Wechsler, value=Honoraria Personal fees relationship with AstraZeneca Please note: years by Michael Wechsler, value=Honoraria Personal fees relationship with GSK Please note: years by Michael Wechsler, value=Honoraria Personal fees relationship with Teva Please note: years by Michael Wechsler, value=Honoraria Board Member relationship with Cytoreason Please note: 2+ years by Michael Wechsler, value=Consulting fee Advisory Committee Member relationship with incyte Please note: 2+ years by Michael Wechsler, value=Consulting fee Consultant relationship with Boehringer INgelheim Please note: 2+ years by Michael Wechsler, value=Consulting fee Board Member relationship with Sentien Please note: 2+ years by Michael Wechsler, value=Consulting fee Consultant relationship with Regeneron Please note: 2+years by Michael Wechsler, value=Consulting fee Consultant relationship with GlaxoSmithKline Please note: 2+ years by Michael Wechsler, value=Grant/Research Support Consultant relationship with Sanofi Please note: 2+ years by Michael Wechsler, value=Consulting fee Consultant relationship with Amgen Please note: 2+ years by Michael Wechsler, value=Consulting fee Consultant relationship with AStrazeneca Please note: 2+ years by Michael Wechsler, value=Consulting fee Consultant relationship with Rapt Therapeutics Regeneron Restorbio Roche/Genentech Sanofi Please note: 2021-2023 Added 03/15/2023 by Michael Wechsler, source=Web Response, value=Consulting fee Consultant relationship with Upstream Bio Please note: 2022 Added 12/01/2022 by Michael Wechsler, source=Web Response, value=stock options Consultant relationship with tetherex Please note: 2022 Added 12/01/2022 by Michael Wechsler, source=Web Response, value=Consulting fee Consultant relationship with Sound Biologics Please note: 2022 Added 12 /01 /2022 by Michael Wechsler, source=Web Response, value=Consulting Consultant relationship with Kinaset Please note: 2022 Added 12/01/2022 by Michael Wechsler, source=Web Response, value=Consulting fee Consultant relationship with Rapt therapeutics Please note: 2022 Added 12/01/2022 by Michael Wechsler, source=Web Response, value=Consulting fee Consultant relationship with Avalo Please note: 2022 Added 12/01/2022 by Michael Wechsler, source=Web Response, value=Consulting fee Consultant relationship with Om pharma Please note: 2022 Added 12/01/2022 by Michael Wechsler, source=Web Response, value=Consulting fee Consultant relationship with Phylaxis Please note: 2022 Added 12/01/2022 by Michael Wechsler, source=Web Response, value=Consulting fee Consultant relationship with Amgen AstraZeneca Avalo Therapeutics Boehringer Ingelheim Please note: 2021-2023 Added 03/15/2023 by Michael Wechsler, source=Web Response, value=Consulting fee Consultant relationship with Cerecor Cohero Health Cytoreason Eli Lilly Equillium Please note: 2021-2023 Added 03/15/2023 by Michael Wechsler, source=Web Response, value=Consulting fee Consultant relationship with Glaxosmithkline Incyte Kinaset Merck Novartis Om Pharma Please note: 2021-2023 Added 03/15/2023 by Michael Wechsler, source=Web Response, value=Consulting fee Consultant relationship with Overtone Therapeutics/Foresite Labs Phylaxis pulmatrix Please note: 2021-2023 Added 03/15/2023 by Michael Wechsler, source=Web Response, value=Consulting fee Consultant relationship with Amgen Please note: 2020- by Michael Wechsler, value=Honoraria Consultant relationship with Sentien Sound Bio Tetherex Pharmaceuticals Teva upstream Please note: 2021-2023 Added 03/15/2023 by Michael Wechsler, source=Web Response, value=Consulting fee Research grants relationship with National Institute of Allergy and Infectious Diseases Please note: N/A Added 03/31/2023 by Michael Wechsler, source=Web Response, value=Grant/Research Support Research grants relationship with The National Heart, Lung, and Blood Institute Please note: N/A Added 03/31/2023 by Michael Wechsler, source=Web Response, value=Grant/Research Support Consultant relationship with GSK Please note: N/A Added 03/31/2023 by Michael Wechsler, source=Web Response, value=Consulting fee Consultant relationship with Genentech Please note: N/A Added 03/31/2023 by Michael Wechsler, source=Web Response, value=Consulting fee Consultant relationship with Sanofi Please note: N/A Added 03/31/2023 by Michael Wechsler, source=Web Response, value=Consulting fee Consultant relationship with Regeneron Please note: N/A Added 03/31/2023 by Michael Wechsler, source=Web Response, value=Consulting fee Consultant relationship with AstraZeneca Please note: N/A Added 03/31/2023 by Michael Wechsler, source=Web Response, value=Consulting fee Consultant relationship with Teva Please note: N/A Added 03/31/2023 by Michael Wechsler, source=Web Response, value=Consulting fee Consultant relationship with Novartis Please note: N/A Added 03/31/2023 by Michael Wechsler, source=Web Response, value=Consulting fee Consultant relationship with Boehringer Ingelheim Please note: N/A Added 03/31/2023 by Michael Wechsler, source=Web Response, value=Consulting fee