Long-term Safety and Clinical Benefit of Mepolizumab in Patients With the Most Severe Eosinophilic Asthma: The COSMEX Study

Clin Ther. 2019 Oct;41(10):2041-2056.e5. doi: 10.1016/j.clinthera.2019.07.007. Epub 2019 Aug 22.


Purpose: The goal of this study was to assess the long-term safety and efficacy of mepolizumab in patients with the most severe eosinophilic asthma.

Methods: This multicenter, open-label, long-term, Phase IIIb study (COSMEX [COSMOS Extension]; 201312/NCT02135692) enrolled patients from the 52-week, open-label extension study COSMOS (A Study to Determine Long-term Safety of Mepolizumab in Asthmatic Subjects) that previously enrolled patients from the double-blinded, placebo-controlled Phase III studies MENSA (Mepolizumab as Adjunctive Therapy in Patients with Severe Asthma) and SIRIUS (Steroid Reduction with Mepolizumab Study). To enter COSMEX, patients had to have life-threatening/seriously debilitating asthma before entering MENSA or SIRIUS and to have completed these previous studies with demonstrated improvement while receiving mepolizumab. In COSMEX, patients received mepolizumab 100 mg subcutaneously every 4 weeks as add-on therapy for up to 172 weeks. Primary endpoints were adverse event frequency and exacerbation rate per year; also assessed were forced expiratory volume in 1 s, Asthma Control Questionnaire-5 score, and daily oral corticosteroid (OCS) use.

Findings: Of the 340 patients enrolled, 339 received mepolizumab; median treatment duration within this extension study was 2.2 years, equating to 718 patient-years of additional exposure. No new safety signals were identified. Patients receiving mepolizumab throughout this study and previous studies had lasting reductions in exacerbation rate and daily OCS use and improvements in forced expiratory volume in 1 s and Asthma Control Questionnaire-5 score. In COSMEX, the on-treatment exacerbation rate (95% CI) was 0.93 (0.81-1.06) event/year for clinically significant exacerbations, 0.13 (0.10-0.18) event/year for exacerbations requiring hospitalization/emergency department visit, and 0.07 (0.05-0.10) event/year for exacerbations requiring hospitalization. In patients requiring systemic/oral corticosteroids with ≥128 weeks of continuous enrollment across SIRIUS, COSMOS, and COSMEX, mepolizumab maintained the median daily OCS dose at 1.3-2.8 mg during COSMEX, with additional patients no longer requiring OCS after extended mepolizumab treatment.

Implications: This study indicates that long-term mepolizumab treatment is well tolerated and associated with sustained clinical benefits in patients with severe eosinophilic asthma. ClinicalTrials.gov identifier: NCT02135692.

Trial registration: ClinicalTrials.gov NCT02135692 NCT01691508 NCT01691521 NCT01842607.

Keywords: asthma exacerbations; corticosteroids; long-term safety; mepolizumab; severe eosinophilic asthma.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adrenal Cortex Hormones / therapeutic use
  • Adult
  • Aged
  • Anti-Asthmatic Agents / administration & dosage*
  • Anti-Asthmatic Agents / therapeutic use
  • Antibodies, Monoclonal, Humanized / administration & dosage*
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Asthma / drug therapy*
  • Eosinophilia / drug therapy*
  • Female
  • Forced Expiratory Volume
  • Humans
  • Male
  • Middle Aged
  • Respiratory Function Tests


  • Adrenal Cortex Hormones
  • Anti-Asthmatic Agents
  • Antibodies, Monoclonal, Humanized
  • mepolizumab

Associated data

  • ClinicalTrials.gov/NCT02135692
  • ClinicalTrials.gov/NCT01691508
  • ClinicalTrials.gov/NCT01691521
  • ClinicalTrials.gov/NCT01842607