title: Long-term Efficacy and Safety of Mepolizumab in Patients With Severe Eosinophilic Asthma: A Multi-center, Open-label, Phase IIIb Study.
abstract: Patients with severe eosinophilic asthma often experience recurrent asthma exacerbations despite intensive inhaled corticosteroid therapy. In 2 previous double-blind studies (MENSA [NCT01691521] and SIRIUS [NCT01691508]), treatment with intravenous or subcutaneous mepolizumab was associated with significantly reduced annualized exacerbation rates and oral corticosteroid (OCS) requirements compared with placebo. The purpose of this study was to assess the long-term safety and efficacy of subcutaneous mepolizumab treatment in patients with severe eosinophilic asthma.
  
  
  
  COSMOS was a 52-week, open-label extension study in patients who received mepolizumab or placebo in MENSA or SIRIUS. Patients received subcutaneous mepolizumab regardless of prior treatment allocation and continued to receive appropriate standard-of-care asthma therapy throughout. The primary objective was to assess the long-term safety of mepolizumab; end points included adverse events (AEs) and serious AEs (SAEs). Efficacy assessments included the annualized exacerbation rate and durability of response (defined as the exacerbation rate and OCS dose reduction when combined with MENSA and SIRIUS data, respectively).
  
  
  
  In total, 558 (86%; previous mepolizumab: 358; previous placebo: 200) and 94 (14%; previous mepolizumab: 58, previous placebo: 36) patients experienced on-treatment AEs and SAEs, respectively. No fatal AEs were reported. Totals of 13 (2%) and 29 (4%) patients experienced systemic and local site reactions, respectively. There were no reports of mepolizumab-related anaphylaxis. Mepolizumab treatment was shown to exert a durable response, with patients who previously received mepolizumab in MENSA or SIRIUS maintaining reductions in exacerbation rate and OCS dosing throughout COSMOS. Patients who previously received placebo in MENSA or SIRIUS demonstrated improvements in these end points following treatment with mepolizumab in COSMOS.
  
  
  
  These data demonstrate a favorable safety profile of mepolizumab and indicate a durable and stable effect over time, supporting long-term treatment in patients with severe eosinophilic asthma. ClinicalTrials.gov identifier: NCT01842607.
authors.affiliation: Duke Asthma, Allergy and Airway Center, Duke Medicine, Durham, North Carolina.
authors.forename: Njira
authors.initials: N
authors.lastname: Lugogo
authors.affiliation: Corporació Sanitària Parc Taulí, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Christian
authors.initials: C
authors.lastname: Domingo
authors.affiliation: Respiratory Medicine, Inserm U1067, Aix-Marseille University, Marseille, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Chanez
authors.affiliation: Airways Inflammation Research Group, Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Richard
authors.initials: R
authors.lastname: Leigh
authors.affiliation: Respiratory Therapeutic Area, GlaxoSmithKline, Stockley Park, Uxbridge, United Kingdom.
authors.forename: Martyn J
authors.initials: MJ
authors.lastname: Gilson
authors.affiliation: Clinical Statistics, GlaxoSmithKline, Stockley Park, Uxbridge, United Kingdom.
authors.forename: Robert G
authors.initials: RG
authors.lastname: Price
authors.affiliation: Respiratory Therapeutic Area, GlaxoSmithKline, Research Triangle Park, North Carolina. Electronic address: steve.w.yancey@gsk.com.
authors.forename: Steven W
authors.initials: SW
authors.lastname: Yancey
authors.affiliation: Respiratory Therapeutic Area, GlaxoSmithKline, Research Triangle Park, North Carolina.
authors.forename: Hector G
authors.initials: HG
authors.lastname: Ortega
mesh_terms: D061605:Administration, Intravenous; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004802:Eosinophilia / Q000188:drug therapy; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D000305:Adrenal Cortex Hormones; D018927:Anti-Asthmatic Agents; D061067:Antibodies, Monoclonal, Humanized; D005938:Glucocorticoids; C434107:mepolizumab
keywords: durability; exacerbations; mepolizumab; safety; severe eosinophilic asthma