PMID- 30359681 OWN - NLM STAT- MEDLINE DCOM- 20200511 LR - 20200511 IS - 1097-6825 (Electronic) IS - 0091-6749 (Linking) VI - 143 IP - 5 DP - 2019 May TI - Assessment of the long-term safety of mepolizumab and durability of clinical response in patients with severe eosinophilic asthma. PG - 1742-1751.e7 LID - S0091-6749(18)31479-9 [pii] LID - 10.1016/j.jaci.2018.09.033 [doi] AB - 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. CI - Copyright (c) 2018 GlaxoSmithKline. Published by Elsevier Inc. All rights reserved. FAU - Khatri, Sumita AU - Khatri S AD - Respiratory Institute, Cleveland Clinic Foundation, Cleveland, Ohio. FAU - Moore, Wendy AU - Moore W AD - Section of Pulmonary, Critical Care, Allergy and Immunologic Disease, Wake Forest School of Medicine, Winston-Salem, NC. FAU - Gibson, Peter G AU - Gibson PG AD - Priority Research Center for Healthy Lungs and Center of Excellence in Severe Asthma, University of Newcastle, Newcastle, Australia. FAU - Leigh, Richard AU - Leigh R AD - Department of Medicine and Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada. FAU - Bourdin, Arnaud AU - Bourdin A AD - Department of Respiratory Diseases PhyMedExp, University of Montpellier, Montpellier, France; Hopital Arnaud de Villeneuve, CHU Montpellier, Montpellier, France. FAU - Maspero, Jorge AU - Maspero J AD - Fundacion Cidea Allergy and Respiratory Research Unit, Buenos Aires, Argentina. FAU - Barros, Manuel AU - Barros M AD - School of Medicine, Universidad de Valparaiso, Valparaiso, Chile; Hospital Carlos van Buren, Valparaiso, Chile. FAU - Buhl, Roland AU - Buhl R AD - Pulmonary Department, Mainz University Hospital, Mainz, Germany. FAU - Howarth, Peter AU - Howarth P AD - 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. FAU - Albers, Frank C AU - Albers FC AD - Respiratory Medical Franchise, GSK, Research Triangle Park, NC. FAU - Bradford, Eric S AU - Bradford ES AD - Respiratory Therapeutic Area, GSK, Research Triangle Park, NC. FAU - Gilson, Martyn AU - Gilson M AD - Respiratory Research and Development, GSK, Uxbridge, Middlesex, United Kingdom. FAU - Price, Robert G AU - Price RG AD - Clinical Statistics, GSK, Stevenage, Hertfordshire, United Kingdom. FAU - Yancey, Steven W AU - Yancey SW AD - Respiratory Therapeutic Area, GSK, Research Triangle Park, NC. FAU - Ortega, Hector AU - Ortega H AD - Respiratory, Medical Affairs, GSK, La Jolla, Calif. Electronic address: hortega@gossamerbio.com. LA - eng SI - ClinicalTrials.gov/NCT01691859 PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial DEP - 20181023 PL - United States TA - J Allergy Clin Immunol JT - The Journal of allergy and clinical immunology JID - 1275002 RN - 0 (Anti-Asthmatic Agents) RN - 0 (Antibodies, Monoclonal, Humanized) RN - 0 (Interleukin-5) RN - 0 (Placebos) RN - 90Z2UF0E52 (mepolizumab) SB - IM MH - Adult MH - Anti-Asthmatic Agents/*therapeutic use MH - Antibodies, Monoclonal, Humanized/*therapeutic use MH - Asthma/*drug therapy MH - Double-Blind Method MH - Drug-Related Side Effects and Adverse Reactions MH - Eosinophilia/*drug therapy MH - Eosinophils/*pathology MH - Female MH - Humans MH - Injections, Subcutaneous MH - Interleukin-5/antagonists & inhibitors MH - Male MH - Middle Aged MH - Placebos MH - Respiratory Tract Infections/etiology MH - Surveys and Questionnaires MH - Treatment Outcome OTO - NOTNLM OT - Mepolizumab OT - extension study OT - long-term safety OT - severe eosinophilic asthma EDAT- 2018/10/26 06:00 MHDA- 2020/05/12 06:00 CRDT- 2018/10/26 06:00 PHST- 2018/07/10 00:00 [received] PHST- 2018/09/07 00:00 [revised] PHST- 2018/09/20 00:00 [accepted] PHST- 2018/10/26 06:00 [pubmed] PHST- 2020/05/12 06:00 [medline] PHST- 2018/10/26 06:00 [entrez] AID - S0091-6749(18)31479-9 [pii] AID - 10.1016/j.jaci.2018.09.033 [doi] PST - ppublish SO - J Allergy Clin Immunol. 2019 May;143(5):1742-1751.e7. doi: 10.1016/j.jaci.2018.09.033. Epub 2018 Oct 23.