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J Allergy Clin Immunol. 2019 May;143(5):1742-1751.e7. doi: 10.1016/j.jaci.2018.09.033. Epub 2018 Oct 23.

Assessment of the long-term safety of mepolizumab and durability of clinical response in patients with severe eosinophilic asthma.

Author information

1
Respiratory Institute, Cleveland Clinic Foundation, Cleveland, Ohio.
2
Section of Pulmonary, Critical Care, Allergy and Immunologic Disease, Wake Forest School of Medicine, Winston-Salem, NC.
3
Priority Research Center for Healthy Lungs and Center of Excellence in Severe Asthma, University of Newcastle, Newcastle, Australia.
4
Department of Medicine and Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
5
Department of Respiratory Diseases PhyMedExp, University of Montpellier, Montpellier, France; Hôpital Arnaud de Villeneuve, CHU Montpellier, Montpellier, France.
6
Fundación Cidea Allergy and Respiratory Research Unit, Buenos Aires, Argentina.
7
School of Medicine, Universidad de Valparaiso, Valparaiso, Chile; Hospital Carlos van Buren, Valparaiso, Chile.
8
Pulmonary Department, Mainz University Hospital, Mainz, Germany.
9
Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton and NIHR Respiratory Biomedical Research Unit, Southampton General Hospital, Southampton, United Kingdom; Global Respiratory Franchise, GSK House, Brentford, Middlesex, United Kingdom.
10
Respiratory Medical Franchise, GSK, Research Triangle Park, NC.
11
Respiratory Therapeutic Area, GSK, Research Triangle Park, NC.
12
Respiratory Research and Development, GSK, Uxbridge, Middlesex, United Kingdom.
13
Clinical Statistics, GSK, Stevenage, Hertfordshire, United Kingdom.
14
Respiratory, Medical Affairs, GSK, La Jolla, Calif. Electronic address: hortega@gossamerbio.com.

Abstract

BACKGROUND:

Mepolizumab has demonstrated favorable safety and efficacy profiles in placebo-controlled trials of 12 months' duration or less; however, long-term data are lacking.

OBJECTIVE:

We sought to evaluate the long-term safety and efficacy of mepolizumab in patients with severe eosinophilic asthma (SEA).

METHODS:

COLUMBA (Open-label Long Term Extension Safety Study of Mepolizumab in Asthmatic Subjects, NCT01691859) was an open-label extension study in patients with SEA previously enrolled in DREAM (Dose Ranging Efficacy And Safety With Mepolizumab in Severe Asthma, NCT01000506). Patients received 100 mg of subcutaneous mepolizumab every 4 weeks plus standard of care until a protocol-defined stopping criterion was met. Safety end points included frequency of adverse events (AEs), serious AEs, and AEs of special interest. Efficacy end points included annualized exacerbation rates, changes from baseline in Asthma Control Questionnaire 5 scores, and blood eosinophil counts. Immunogenicity was also assessed.

RESULTS:

Overall, 347 patients were enrolled for an average of 3.5 years (maximum, 4.5 years; total exposure, 1201 patient-years). On-treatment AEs were reported in 94% of patients (exposure-adjusted rate, 3688 events/1000 patient-years). The most frequently reported on-treatment AEs were respiratory tract infection, headache, bronchitis, and asthma worsening. Seventy-nine (23%) patients experienced 1 or more on-treatment serious AEs; there were 6 deaths, none of which were assessed as related to mepolizumab. For patients with 156 weeks or greater enrollment, the exacerbation rate was 0.74 events/y (weeks 0-156), a 56% reduction from the off-treatment period between DREAM and COLUMBA. For all patients, at the first postbaseline assessment, the mean Asthma Control Questionnaire 5 score was reduced by 0.47 points, and blood eosinophil counts were reduced by 78%, with similar improvements maintained throughout the study. The immunogenicity profile (8% anti-drug antibodies) was consistent with previous studies.

CONCLUSION:

These data support the long-term safety and efficacy of mepolizumab in patients with SEA.

KEYWORDS:

Mepolizumab; extension study; long-term safety; severe eosinophilic asthma

PMID:
30359681
DOI:
10.1016/j.jaci.2018.09.033
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