Abstract / Summary
Background Mepolizumab reduces relapses and glucocorticoid exposure in hypereosinophilic syndrome (HES), but evidence on long-term effectiveness remains limited. Growing consensus emphasizes sustained low disease activity over single-timepoint response in chronic inflammatory diseases. Objective To evaluate the long-term safety and effectiveness of mepolizumab in HES using a pragmatic definition of Eosinophilic Low Disease Activity State (EoLDAS). Methods We conducted a retrospective multicenter study of 67 patients with glucocorticoid-responsive FIP1L1::PDGFRA -negative HES treated with mepolizumab between 2003 and 2022 through clinical trials or compassionate use programs. Clinical manifestations, blood eosinophil counts, treatments, and serious adverse events were assessed at three-month intervals. EoLDAS was defined as absence of relapse, an absolute eosinophil count <0.5×10 9 /L (complete hematologic response, [CHR]), and a prednisone dose ≤5 mg/day. Results After a median follow-up of 51 months, 12 patients (18%) relapsed and CHR was maintained during a median of 93% of visits. Patients spent a median of 79% (IQR, 40–88) of follow-up visits in EoLDAS, and 51% maintained EoLDAS for at least 75% of visits. Poor EoLDAS attainment (<25% of visits; n=11) was associated with lymphocytic HES and more prior treatment lines. Extending mepolizumab dosing intervals was associated with modest increases in eosinophil counts, but not with relapse or increased glucocorticoid exposure. No serious adverse event was considered related to mepolizumab. Conclusion Mepolizumab provided sustained long-term disease control with low glucocorticoid exposure in FIP1L1::PDGFRA -negative HES. EoLDAS offers a pragmatic measure of longitudinal disease control that warrants prospective validation and may inform future treat-to-target strategies.