EFFICACY OF MEPOLIZUMAB IN PATIENTS WITH EOSINOPHILIC GRANULOMATOSIS WITH POLYANGIITIS AND A VASCULITIC PHENOTYPE
Authors: Lee Baylis et al.
Patients with eosinophilic granulomatosis with polyangiitis (EGPA) can have vasculitic or eosinophilic phenotypes. The MIRRA study demonstrated that patients with EGPA spent more time in remission and had reduced oral corticosteroid (OCS) use with mepolizumab vs placebo (PBO). This analysis evaluated mepolizumab in patients with a vasculitic phenotype enrolled in MIRRA.
MIRRA was a phase III RCT comparing mepolizumab (300 mg SC Q4W) with PBO for 52 weeks in adults with relapsing / refractory EGPA. The primary endpoints were accrued weeks of remission and OCS dose ≤4 mg/day prednisolone over 52 weeks. This post hoc analysis evaluated the endpoints according to antineutrophil cytoplasmic antibody (MPO-/PR3-ANCA) at study baseline, baseline Birmingham Vasculitis Activity Score (BVAS) and Vasculitis Damage Index (VDI) score. Types of disease relapse (vasculitis [BVAS >0], asthma and sinonasal disease reported during the treatment period were described. EGPA disease characteristics focusing on vasculitic components were assessed.
Of 136 patients, 26 (19%) had a history of a positive ANCA test at study baseline. 85 (63%) had BVAS >0 and 62 (46%) had VDI ≥5. Accrued remission duration was greater with mepolizumab vs PBO, irrespective of ANCA positivity, baseline BVAS or baseline VDI. Across all subgroups, a larger proportion achieved remission at weeks 36 and 48 with mepolizumab vs PBO. Mepolizumab reduced all types of disease relapse assessed during the treatment period, including vasculitis, asthma and sinonasal relapses, vs PBO. Vasculitic characteristics including neuropathy, glomerulonephritis, alveolar haemorrhage, palpable purpura and ANCA positivity were generally similar among those who did and did not achieve remission during the study.
This posthoc analysis shows a positive effect of Mepolizumab on the vasculitic type of eGPA. The numbers are small and the data do not suggest replacing immune-suppressive treatment by Mepolizumab. But they confirm a powerful effect of this anti-IL-5 agent on eosinophilia and related clinical manifestations.