POS0836 EFFICACY OF MEPOLIZUMAB IN PATIENTS WITH EOSINOPHILIC GRANULOMATOSIS WITH POLYANGIITIS AND A VASCULITIC PHENOTYPE

Abstract

BackgroundPatients with eosinophilic granulomatosis with polyangiitis (EGPA) can present with vasculitic or eosinophilic phenotypes.1 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.2ObjectivesTo evaluate the efficacy of mepolizumab in patients with a vasculitic EGPA phenotype enrolled in the MIRRA study.MethodsMIRRA was a Phase III, multicentre, double-blind, parallel-group trial in adult patients with relapsing/refractory EGPA and ≥4 weeks stable OCS treatment. Patients were randomised to receive standard of care plus mepolizumab (300 mg 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 ≤4 mg/day prednisolone or equivalent) over the 52-week study period categorised in weeks (0, >0 to <12, 12 to <24, 24 to <36 and ≥36 weeks), and the proportion of patients in remission at both Weeks 36 and 48. This post hoc analysis used data from the MIRRA study to evaluate these endpoints according to patients’ antineutrophil cytoplasmic antibody (ANCA) history (current or previous positive test for myeloperoxidase[MPO]/proteinase 3[PR3]-ANCA at study baseline versus no history of a positive MPO/PR3-ANCA test at baseline), baseline BVAS (=0 vs >0) and Vasculitis Damage Index (VDI) score (<5 vs ≥5). Types of disease relapse (vasculitis [BVAS >0], asthma [active asthma symptoms and/or signs with a worsening in Asthma Control Questionnaire-6 score] and sinonasal [active nasal and/or sinus disease with a worsening in ≥1 sinonasal symptom questions]) reported during the treatment period were also described. EGPA disease characteristics focusing on vasculitic components were assessed in patients who did and did not achieve remission at any point during the study.ResultsOf 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 while 85 (63%) had a BVAS >0; 74 (54%) had a VDI <5 at baseline and 62 (46%) had a VDI ≥5. Accrued remission duration was greater with mepolizumab versus placebo, irrespective of ANCA positive status, baseline BVAS or baseline VDI score (Figure 1). Across all the subgroups, a larger proportion of patients achieved remission at both Weeks 36 and 48 with mepolizumab versus placebo (Figure 1). 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.Figure 1.Mepolizumab efficacy by patient baseline characteristicsANCA, antineutrophil cytoplasmic antibody; BVAS, Birmingham Vasculitis Activity Score; CI, confidence interval; NA, data not available – estimate could not be calculated owing to a lack of patients in the placebo group achieving remission at Weeks 36 and 48; VDI, Vasculitis Damage Index.ConclusionMepolizumab is associated with clinical benefits in patients with EGPA, including those with and without a vasculitic phenotype.