Abstract
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 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 (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.