EFFICACY OF MEPOLIZUMAB IN PATIENTS WITH EOSINOPHILIC GRANULOMATOSIS WITH POLYANGIITIS AND A VASCULITIC PHENOTYPE
Authors: Terrier B. et al.
Patients with eosinophilic granulomatosis with polyangiitis (EGPA) can present with vasculitic or with eosinophilic phenotypes. The Phase III MIRRA study demonstrated that patients with EGPA spent more time in remission and had reduced oral corticosteroid (OCS) use with mepolizumab versus placebo. Mepolizumab neutralizes IL-5 which is the key growth factor of eosinophils. Whether blockade of IL-5 is sufficient to control vasculitis or merely eliminates eosinophils has not been sufficiently addressed.
Patients received standard of care plus mepolizumab (300mg subcutaneously every 4 weeks) or placebo for 52 weeks. Primary endpoints were: accrued weeks of remission (defined as Birmingham Vasculitis Activity Score [BVAS] of 0 and OCS dose ≤4mg/day prednisolone or equivalent) and Vasculitis Damage Index (VDI) score (0], asthma and sinonasal disease. EGPA disease characteristics focusing on vasculitic components were assessed in patients who did and did not achieve remission at any point during the study.
Of the 136 patients in the study, 26 (19%) had a history of a positive ANCA test at study baseline and 110 (81%) did not. In addition, 51 (38%) had a BVAS =0 at baseline; 74 (54%) had a VDI <5 at baseline. Accrued remission duration was greater with mepolizumab versus placebo, irrespective of ANCA positive status, baseline BVAS or baseline VDI score. Across all the subgroups, a larger proportion of patients achieved remission at both weeks 36 and 48 with mepolizumab versus placebo. Among patients receiving mepolizumab, the numbers (proportion) of patients achieving remission at both weeks 36 and 48 were: 7 (54%) for patients with a history of an ANCA-positive test and 15 (27%) for patients without a history of an ANCA-positive test; 14 (45%) in the BVAS =0 and 8 (22%) in the BVAS >0 groups; 11 (29%) in the VDI score <5 and 11 (37%) in the VDI score ≥5 groups.
Mepolizumab reduced all types of disease relapse assessed during the treatment period, including vasculitis, asthma and sinonasal relapses, compared with placebo. Vasculitic characteristics including neuropathy, glomerulonephritis, alveolar haemorrhage, palpable purpura and ANCA positivity were generally similar among patients who did and did not achieve remission during the study.
In summary, this additional analysis of the MIRRA study shows that Mepolizumab is associated with clinical benefits in patients with and without a vasculitic phenotype. Still, the numbers are small and uncertainties remain. Only 20% of patients were ANCA positive and only 7 ANCA positive patients achieved a sustained remission. Also, it will be of interest to learn which %-age of patients remains in long-term, drug-free remission.