TY - JOUR
T1 - Mepolizumab for urban children with exacerbation-prone eosinophilic asthma in the USA (MUPPITS-2)
T2 - a randomised, double-blind, placebo-controlled, parallel-group trial
AU - US National Institute of Allergy and Infectious Disease's Inner City Asthma Consortium
AU - Jackson, Daniel J.
AU - Bacharier, Leonard B.
AU - Gergen, Peter J.
AU - Gagalis, Lisa
AU - Calatroni, Agustin
AU - Wellford, Stephanie
AU - Gill, Michelle A.
AU - Stokes, Jeffrey
AU - Liu, Andrew H.
AU - Gruchalla, Rebecca S.
AU - Cohen, Robyn T.
AU - Makhija, Melanie
AU - Khurana Hershey, Gurjit K.
AU - O'Connor, George T.
AU - Pongracic, Jacqueline A.
AU - Sherenian, Michael G.
AU - Rivera-Spoljaric, Katherine
AU - Zoratti, Edward M.
AU - Teach, Stephen J.
AU - Kattan, Meyer
AU - Dutmer, Cullen M.
AU - Kim, Haejin
AU - Lamm, Carin
AU - Sheehan, William J.
AU - Segnitz, R. Max
AU - Dill-McFarland, Kimberly A.
AU - Visness, Cynthia M.
AU - Becker, Patrice M.
AU - Gern, James E.
AU - Sorkness, Christine A.
AU - Busse, William W.
AU - Altman, Matthew C.
N1 - Funding Information:
The research reported in this publication was supported by NIH-NIAID award numbers 5UM1AI114271, UM1AI160040, and UM2AI117870, with additional support provided through award numbers UL1TRG01422, UL1RR025741, UL1TR000150, UL1TR001422, UL1 TR002535, UL1TR001876, and 5UL1TR001425–03. Additional support was also provided through an unrestricted grant from GlaxoSmithKline. The manuscript content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
Funding Information:
The research reported in this publication was supported by NIH-NIAID award numbers 5UM1AI114271, UM1AI160040, and UM2AI117870, with additional support provided through award numbers UL1TRG01422, UL1RR025741, UL1TR000150, UL1TR001422, UL1 TR002535, UL1TR001876, and 5UL1TR001425–03. Additional support was also provided through an unrestricted grant from GlaxoSmithKline. The manuscript content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
Publisher Copyright:
© 2022 Elsevier Ltd
PY - 2022/8/13
Y1 - 2022/8/13
N2 - Background: Black and Hispanic children living in urban environments in the USA have an excess burden of morbidity and mortality from asthma. Therapies directed at the eosinophilic phenotype reduce asthma exacerbations in adults, but few data are available in children and diverse populations. Furthermore, the molecular mechanisms that underlie exacerbations either being prevented by, or persisting despite, immune-based therapies are not well understood. We aimed to determine whether mepolizumab, added to guidelines-based care, reduced the number of asthma exacerbations during a 52-week period compared with guidelines-based care alone. Methods: This is a randomised, double-blind, placebo-controlled, parallel-group trial done at nine urban medical centres in the USA. Children and adolescents aged 6–17 years, who lived in socioeconomically disadvantaged neighbourhoods and had exacerbation-prone asthma (defined as ≥two exacerbations in the previous year) and blood eosinophils of at least 150 cells per μL were randomly assigned 1:1 to mepolizumab (6–11 years: 40 mg; 12–17 years: 100 mg) or placebo injections once every 4 weeks, plus guideline-based care, for 52 weeks. Randomisation was done using a validated automated system. Participants, investigators, and the research staff who collected outcome measures remained masked to group assignments. The primary outcome was the number of asthma exacerbations that were treated with systemic corticosteroids during 52 weeks in the intention-to-treat population. The mechanisms of treatment response were assessed by study investigators using nasal transcriptomic modular analysis. Safety was assessed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT03292588. Findings: Between Nov 1, 2017, and Mar 12, 2020, we recruited 585 children and adolescents. We screened 390 individuals, of whom 335 met the inclusion criteria and were enrolled. 290 met the randomisation criteria, were randomly assigned to mepolizumab (n=146) or placebo (n=144), and were included in the intention-to-treat analysis. 248 completed the study. The mean number of asthma exacerbations within the 52-week study period was 0·96 (95% CI 0·78–1·17) with mepolizumab and 1·30 (1·08–1·57) with placebo (rate ratio 0·73; 0·56–0·96; p=0·027). Treatment-emergent adverse events occurred in 42 (29%) of 146 participants in the mepolizumab group versus 16 (11%) of 144 participants in the placebo group. No deaths were attributed to mepolizumab. Interpretation: Phenotype-directed therapy with mepolizumab in urban children with exacerbation-prone eosinophilic asthma reduced the number of exacerbations. Funding: US National Institute of Allergy and Infectious Diseases and GlaxoSmithKline.
AB - Background: Black and Hispanic children living in urban environments in the USA have an excess burden of morbidity and mortality from asthma. Therapies directed at the eosinophilic phenotype reduce asthma exacerbations in adults, but few data are available in children and diverse populations. Furthermore, the molecular mechanisms that underlie exacerbations either being prevented by, or persisting despite, immune-based therapies are not well understood. We aimed to determine whether mepolizumab, added to guidelines-based care, reduced the number of asthma exacerbations during a 52-week period compared with guidelines-based care alone. Methods: This is a randomised, double-blind, placebo-controlled, parallel-group trial done at nine urban medical centres in the USA. Children and adolescents aged 6–17 years, who lived in socioeconomically disadvantaged neighbourhoods and had exacerbation-prone asthma (defined as ≥two exacerbations in the previous year) and blood eosinophils of at least 150 cells per μL were randomly assigned 1:1 to mepolizumab (6–11 years: 40 mg; 12–17 years: 100 mg) or placebo injections once every 4 weeks, plus guideline-based care, for 52 weeks. Randomisation was done using a validated automated system. Participants, investigators, and the research staff who collected outcome measures remained masked to group assignments. The primary outcome was the number of asthma exacerbations that were treated with systemic corticosteroids during 52 weeks in the intention-to-treat population. The mechanisms of treatment response were assessed by study investigators using nasal transcriptomic modular analysis. Safety was assessed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT03292588. Findings: Between Nov 1, 2017, and Mar 12, 2020, we recruited 585 children and adolescents. We screened 390 individuals, of whom 335 met the inclusion criteria and were enrolled. 290 met the randomisation criteria, were randomly assigned to mepolizumab (n=146) or placebo (n=144), and were included in the intention-to-treat analysis. 248 completed the study. The mean number of asthma exacerbations within the 52-week study period was 0·96 (95% CI 0·78–1·17) with mepolizumab and 1·30 (1·08–1·57) with placebo (rate ratio 0·73; 0·56–0·96; p=0·027). Treatment-emergent adverse events occurred in 42 (29%) of 146 participants in the mepolizumab group versus 16 (11%) of 144 participants in the placebo group. No deaths were attributed to mepolizumab. Interpretation: Phenotype-directed therapy with mepolizumab in urban children with exacerbation-prone eosinophilic asthma reduced the number of exacerbations. Funding: US National Institute of Allergy and Infectious Diseases and GlaxoSmithKline.
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U2 - 10.1016/S0140-6736(22)01198-9
DO - 10.1016/S0140-6736(22)01198-9
M3 - Article
C2 - 35964610
AN - SCOPUS:85135937418
SN - 0140-6736
VL - 400
SP - 502
EP - 511
JO - The Lancet
JF - The Lancet
IS - 10351
ER -
