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Subcutaneous mepolizumab in children aged 6 to 11 years with severe eosinophilic asthma.

Abstract

OBJECTIVES

There are no published reports for anti-interleukin-5 therapy in children <12 years with asthma. The primary objective of this study was to characterize the pharmacokinetics and pharmacodynamics of mepolizumab following subcutaneous (SC) administration in children 6 to 11 years-of-age with severe eosinophilic asthma.

HYPOTHESIS

Mepolizumab SC pharmacokinetics and pharmacodynamics in children with severe eosinophilic asthma are comparable with adults.

STUDY DESIGN

Multinational, nonrandomised, open-label (NCT02377427).

PATIENT SELECTION

Children 6 to 11 years-of-age with severe eosinophilic asthma (blood eosinophil count ≥150 cells/µL at screening or ≥300 cells/µL <12 months of screening) and ≥2 exacerbations in the prior year.

METHODOLOGY

Children received mepolizumab SC 40 mg (bodyweight <40 kg) or 100 mg (≥40 kg) every 4 weeks for 12 weeks.

RESULTS

Thirty-six children received mepolizumab (40 mg, n = 26; 100 mg, n = 10). Mepolizumab exposures were higher and apparent clearance lower than predicted based on prior existing data. Derived mepolizumab exposures normalized to mean bodyweight for the 40 mg and 100 mg dose groups were 454 μg * day/mL and 675 μg * day/mL, respectively. At week 12, blood eosinophils were reduced by 89% and 83% from baseline to 42 and 55 cells/µL, respectively. Mepolizumab was well tolerated; no new safety signals were observed compared with previous adult/adolescent studies.

CONCLUSION

In children 6 to 11 years-of-age with severe eosinophilic asthma, mepolizumab SC 40 or 100 mg provided bodyweight-adjusted drug exposure within twofold of target adult exposure as well as marked reductions to blood eosinophil counts similar to adults, and although not designed to evaluate efficacy outcomes, demonstrated a positive clinical profile.

Authors+Show Affiliations

King's College Hospital NHS Foundation Trust, King's College London, London, UK.Clinical Pharmacology Modelling and Simulation, GSK, Uxbridge, Middlesex, UK.Clinical Pharmacology Modelling and Simulation, GSK, Uxbridge, Middlesex, UK.Clinical Statistics, GSK, Stevenage, Hertfordshire, UK.Clinical Pharmacology Modelling and Simulation, R&D Medicines Research Centre, GSK, Stevenage, Hertfordshire, UK.Respiratory TAU & Flexible Discovery Unit, GSK, Philadelphia, Pennsylvania.Respiratory Therapeutic Area, GSK, Research Triangle Park, North Carolina.Respiratory Therapeutic Area, GSK, Research Triangle Park, North Carolina.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31502421

Citation

Gupta, Atul, et al. "Subcutaneous Mepolizumab in Children Aged 6 to 11 Years With Severe Eosinophilic Asthma." Pediatric Pulmonology, 2019.
Gupta A, Pouliquen I, Austin D, et al. Subcutaneous mepolizumab in children aged 6 to 11 years with severe eosinophilic asthma. Pediatr Pulmonol. 2019.
Gupta, A., Pouliquen, I., Austin, D., Price, R. G., Kempsford, R., Steinfeld, J., ... Yancey, S. W. (2019). Subcutaneous mepolizumab in children aged 6 to 11 years with severe eosinophilic asthma. Pediatric Pulmonology, doi:10.1002/ppul.24508.
Gupta A, et al. Subcutaneous Mepolizumab in Children Aged 6 to 11 Years With Severe Eosinophilic Asthma. Pediatr Pulmonol. 2019 Sep 9; PubMed PMID: 31502421.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Subcutaneous mepolizumab in children aged 6 to 11 years with severe eosinophilic asthma. AU - Gupta,Atul, AU - Pouliquen,Isabelle, AU - Austin,Daren, AU - Price,Robert G, AU - Kempsford,Rodger, AU - Steinfeld,Jonathan, AU - Bradford,Eric S, AU - Yancey,Steven W, Y1 - 2019/09/09/ PY - 2018/12/21/received PY - 2019/08/25/accepted PY - 2019/9/11/entrez KW - asthma and early wheeze KW - children KW - severe eosinophilic asthma KW - subcutaneous mepolizumab JF - Pediatric pulmonology JO - Pediatr. Pulmonol. N2 - OBJECTIVES: There are no published reports for anti-interleukin-5 therapy in children <12 years with asthma. The primary objective of this study was to characterize the pharmacokinetics and pharmacodynamics of mepolizumab following subcutaneous (SC) administration in children 6 to 11 years-of-age with severe eosinophilic asthma. HYPOTHESIS: Mepolizumab SC pharmacokinetics and pharmacodynamics in children with severe eosinophilic asthma are comparable with adults. STUDY DESIGN: Multinational, nonrandomised, open-label (NCT02377427). PATIENT SELECTION: Children 6 to 11 years-of-age with severe eosinophilic asthma (blood eosinophil count ≥150 cells/µL at screening or ≥300 cells/µL <12 months of screening) and ≥2 exacerbations in the prior year. METHODOLOGY: Children received mepolizumab SC 40 mg (bodyweight <40 kg) or 100 mg (≥40 kg) every 4 weeks for 12 weeks. RESULTS: Thirty-six children received mepolizumab (40 mg, n = 26; 100 mg, n = 10). Mepolizumab exposures were higher and apparent clearance lower than predicted based on prior existing data. Derived mepolizumab exposures normalized to mean bodyweight for the 40 mg and 100 mg dose groups were 454 μg * day/mL and 675 μg * day/mL, respectively. At week 12, blood eosinophils were reduced by 89% and 83% from baseline to 42 and 55 cells/µL, respectively. Mepolizumab was well tolerated; no new safety signals were observed compared with previous adult/adolescent studies. CONCLUSION: In children 6 to 11 years-of-age with severe eosinophilic asthma, mepolizumab SC 40 or 100 mg provided bodyweight-adjusted drug exposure within twofold of target adult exposure as well as marked reductions to blood eosinophil counts similar to adults, and although not designed to evaluate efficacy outcomes, demonstrated a positive clinical profile. SN - 1099-0496 UR - https://www.unboundmedicine.com/medline/citation/31502421/Subcutaneous_mepolizumab_in_children_aged_6_to_11_years_with_severe_eosinophilic_asthma L2 - https://doi.org/10.1002/ppul.24508 DB - PRIME DP - Unbound Medicine ER -