gms | German Medical Science

Introduction: The MIRRA study demonstrated that patients with eosinophilic granulomatosis with polyangiitis (EGPA) spent longer in remission and had reduced oral corticosteroid (OCS) use with mepolizumab versus placebo [1]. Here we assess the efficacy of mepolizumab in patients with a vasculitic EGPA phenotype enrolled in MIRRA.

Methods: MIRRA was a Phase III, multicentre, double-blind, parallel-group trial in adults with relapsing/refractory EGPA and ≥4 weeks stable OCS treatment. Patients were randomised to receive 4-weekly mepolizumab 300 mg subcutaneously or placebo plus standard of care for 52 weeks. Co-primary endpoints assessed: accrued duration of remission (Birmingham Vasculitis Activity Score [BVAS]=0 and OCS dose ≤4 mg/day) categorised as 0, >0–<12, 12–<24, 24–<36 and ≥36 weeks; proportion of patients in remission at Weeks 36 and 48. This post hoc analysis assessed the endpoints stratified by patient’s history of a positive antineutrophil cytoplasmic antibody (ANCA) test (history/no history), baseline BVAS (=0/>0) and Vasculitis Damage Index (VDI) score (<5/≥5). Total accrued duration of BVAS=0 over 52 weeks, proportion of patients who achieved BVAS=0 at Weeks 36 and 48 and patient characteristics (based on historical EGPA diagnosis ) by remission status were also described.

Results: Overall, 136 patients were included in the analysis. At baseline, most patients (110[81%]) had no history of an ANCA positive test and had a BVAS>0 (85[63%]); over half had a VDI score <5 (74[54%]). Patients treated with mepolizumab had greater accrued duration of remission versus placebo, irrespective of ANCA positive status, baseline BVAS or VDI score. Across all subgroups, a larger proportion of patients achieved remission at Weeks 36 and 48 with mepolizumab versus placebo (Figure 1 [Fig. 1]). Patients treated with mepolizumab had greater accrued duration of BVAS=0 versus placebo (OR[95% CI]:3.71[1.82,7.60]). At Weeks 36 and 48, a greater proportion of patients treated with mepolizumab achieved BVAS=0 versus placebo (34[50%] vs 23[34%]; OR[95%CI]: 1.94 [0.90,4.19]). Historical vasculitic-associated organ manifestations including neuropathy, glomerulonephritis, alveolar haemorrhage, palpable purpura and ANCA positivity were similar among patients who achieved/did not achieve remission during the study.

Conclusion: Mepolizumab is associated with clinical benefits in patients with EGPA, including those with and without a vasculitic phenotype.

Disclosures: The parent study [GSK ID: MEA115921/NCT02020889] and this post hoc analysis were funded by GSK. Benjamin Terrier: has received consulting fees from Roche, Chugai, GSK, AstraZeneca, Bristol Myers Squibb, Terumo BCT, Sanofi, LFB and Grifols. David RW Jayne: has received research grants and consultancy fees from AstraZeneca, Aurinia, BMS, Boehringer Ingelheim, ChemoCentryx, GSK, Janssen, Novartis, Roche/Genentech, Takeda and Vifor. Bernhard Hellmich: has been an investigator in clinical trials for Ab2Bio, AbbVie, AstraZeneca, Bristol Myers Squibb, ChemoCentryx, GSK, InflaRx, Kiniksa, Nippon Kayaku, Novartis, Roche and Sanofi. He has acted as a consultant, advisory board member and/or lecturer for AbbVie, BMS, Boehringer Ingelheim, Chugai, GSK, InflaRx, Novartis, Pfizer, Roche and Vifor Pharma. Jane H Bentley: employee of GSK and owns stocks/shares in GSK. Jonathan Steinfeld: was an employee of GSK at the time of the study and owns stocks/shares in GSK. Steven W Yancey: employee of GSK and owns stocks/shares in GSK. Namhee Kwon: employee of GSK and owns stocks/shares in GSK. Natalie Zimmermann: employee of GSK and owns stocks/shares in GSK. Praveen Akuthota: declares advisory board membership and research funding from GSK, consultancy, advisory board membership and research funding from AstraZeneca and Regeneron, and declares consultancy fees paid to PA’s institution from AstraZeneca and Sanofi. PA is also an Assembly Program Committee Volunteer for the American Thoracic Society. Paneez Khoury: declares no conflicts of interest. Lee Baylis: employee of GSK and owns stocks/shares in GSK. Michael E Wechsler: has research grants with the National Institute of Allergy and Infectious Diseases and the National Heart, Lung, and Blood Institute and is a consultant with GSK, Genentech, Sanofi, Regeneron, AstraZeneca, Teva, Novartis, Boehringer Ingelheim, Sentien and Equillium.