The Journal of allergy and clinical immunology · 2026
Mepolizumab long-term remodeling effect in severe asthma responders: the MESILICO study.
СтатьяНазвание и аннотация: Перевод в очереди
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Porpodis Konstantinos, Tsiouprou Ioanna, Bakakos Petros, Grigoris Stratakos, Argyrios Tzouvelekis, Steiropoulos Paschalis, Katsoulis Konstantinos, Kostikas Konstantinos, Antoniou Katerina M, Papaioannou Andriana I, Rovina Nikoletta, Katsaounou Paraskevi, Pastelli Nicoleta, Tryfon Stavros, Fouka Evangelia, Tzanakis Nikolaos, Loukides Stelios, Domvri Kalliopi
Аннотация
BACKGROUND: MESILICO study has provided evidence on the effect of mepolizumab, an anti-IL-5 biologic, on airway remodeling in severe asthma at 12 months post-treatment (NCT04612556).
OBJECTIVE: We continued to investigate the longer-term effect of mepolizumab on airway structural remodeling.
METHODS: Forty-seven patients were recruited, who initiated mepolizumab, of whom 41 were enrolled in the bronchoscopy sub-study. At 3-years the participants underwent further bronchoscopic airway sampling and remodeling indices were measured, along with sub-mucosal eosinophils, tissue immunoexpression of Muc-5AC, E-cadherin and number of FOXP3+ regulatory-like cells.
RESULTS: Thirty-five patients of the initial 47 cohort completed 3 years of treatment, associated with significant improvements in lung function, in biomarkers and a decrease in exacerbation events (p<0.05). Twenty-five of the 41 patients enrolled in the sub-study were submitted to bronchoscopy post 3-years of treatment. There was a significant sustained reduction from baseline in sub-basement membrane thickness, airway smooth muscle area and layer thickness and epithelial damage, as well as a decrease in tissue eosinophil numbers (all p<0.001). Additional improvements were seen at 3 years for Muc-5AC and E-cadherin histoscores and FOXP3+ regulatory-like cells.
CONCLUSIONS: This is the first study supporting the possibility that sustained IL-5 blockade may contribute to long-term structural airway improvement and may be consistent with disease modification in severe eosinophilic asthma.
OBJECTIVE: We continued to investigate the longer-term effect of mepolizumab on airway structural remodeling.
METHODS: Forty-seven patients were recruited, who initiated mepolizumab, of whom 41 were enrolled in the bronchoscopy sub-study. At 3-years the participants underwent further bronchoscopic airway sampling and remodeling indices were measured, along with sub-mucosal eosinophils, tissue immunoexpression of Muc-5AC, E-cadherin and number of FOXP3+ regulatory-like cells.
RESULTS: Thirty-five patients of the initial 47 cohort completed 3 years of treatment, associated with significant improvements in lung function, in biomarkers and a decrease in exacerbation events (p<0.05). Twenty-five of the 41 patients enrolled in the sub-study were submitted to bronchoscopy post 3-years of treatment. There was a significant sustained reduction from baseline in sub-basement membrane thickness, airway smooth muscle area and layer thickness and epithelial damage, as well as a decrease in tissue eosinophil numbers (all p<0.001). Additional improvements were seen at 3 years for Muc-5AC and E-cadherin histoscores and FOXP3+ regulatory-like cells.
CONCLUSIONS: This is the first study supporting the possibility that sustained IL-5 blockade may contribute to long-term structural airway improvement and may be consistent with disease modification in severe eosinophilic asthma.