Mepolizumab Initiation by Day 30 and Glucocorticoid Exposure in Newly Diagnosed EGPA: a Single-Center 30-Day Landmark Cohort Study.

Evidence on mepolizumab soon after glucocorticoid initiation in newly diagnosed eosinophilic granulomatosis with polyangiitis (EGPA) is limited. We compared nonrandomized initial treatment strategies defined by mepolizumab initiation within 30 days after glucocorticoid initiation with respect to post-landmark oral glucocorticoid exposure. We performed a single-center pilot retrospective cohort study of 30 patients with newly diagnosed EGPA who started systemic glucocorticoids. Primary analyses used a 30-day landmark cohort of 27 patients who remained under observation through day 30. Patients were classified into a mepolizumab-by-day-30 group and a no-mepolizumab-by-day-30 group; the latter comprised patients without initiation by day 30, regardless of later initiation. The primary outcome was cumulative oral prednisolone exposure from day 30 to 12 months. The landmark cohort included 6 patients in the mepolizumab-by-day-30 group and 21 in the no-mepolizumab-by-day-30 group. Cumulative oral prednisolone exposure from day 30 to 12 months was lower in the mepolizumab-by-day-30 group than in the no-mepolizumab-by-day-30 group (24.7 vs. 68.6 mg/kg). Similar differences were seen from day 30 to 6 months (17.6 vs. 43.6 mg/kg) and in oral prednisolone dose at 12 months (0.03 vs. 0.12 mg/kg/day). When intravenous methylprednisolone pulse therapy was added using observed dose and duration as prednisolone-equivalent systemic glucocorticoid exposure, the between-group difference was attenuated, especially over 0–6 months. By 3 months, the Birmingham Vasculitis Activity Score was 0 in all evaluable patients in both groups, and remission differences mainly reflected attainment of prednisolone ≤ 7.5 mg/day. In this single-center pilot cohort comparing nonrandomized initial treatment strategies, mepolizumab initiation within 30 days after glucocorticoid initiation was associated with lower post-landmark oral glucocorticoid exposure. These findings are hypothesis-generating and do not isolate the causal effect of mepolizumab from calendar-time, treatment-indication, or concomitant-treatment differences.