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A1372 - Durability of Clinical Response Following Long-Term Treatment with Mepolizumab in Patients with Severe Eosinophilic Asthma: The COLUMBA Study
Author Block: F. C. Albers1, H. Ortega2, E. S. Bradford3, M. J. Gilson4, R. G. Price5, S. W. Yancey3, W. C. Moore6; 1Respiratory Medical Franchise, GSK, Research Triangle Park, NC, United States, 2Respiratory, Medical Affairs, GSK, La Jolla, CA, United States, 3Respiratory Therapeutic Area, GSK, Research Triangle Park, NC, United States, 4Respiratory Research and Development, GSK, Stockley Park, United Kingdom, 5Clinical Statistics, GSK, Stockley Park, United Kingdom, 6Pulmonary Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, United States.
Rationale: There are limited data on the long-term efficacy of anti-interleukin-5 biologics, such as mepolizumab, in patients with severe eosinophilic asthma (SEA). One of the objectives of COLUMBA was to assess the durability of clinical response to mepolizumab in patients with SEA, when treated for up to 4.5 years. Methods: COLUMBA was a long-term, open-label extension study that recruited patients with SEA who had previously participated in the DREAM study [1]. Patients received 100 mg subcutaneous mepolizumab every 4 weeks in addition to standard care, until a protocol-defined stopping criteria was met, such as mepolizumab becoming commercially available. Endpoints included the frequency of exacerbations, Asthma Control Questionnaire (ACQ)-5 score, pre-bronchodilator forced expiratory volume in 1 second (FEV1), and peripheral blood eosinophil count. ACQ-5 and lung function were measured at baseline and every 12 to 24 weeks subsequently until the end of the treatment period. Results: In total, 347 patients were enrolled (mean age 52 years; 65% female; 90% Caucasian; mean body mass index 28.6 kg/m2) and received mepolizumab for an average of 3.5 years (maximum 4.5 years). Overall, 944 on-treatment exacerbations were reported in 231 (67%) patients. The exacerbation rate during the treatment period was 0.68 events/year (95% confidence interval 0.60, 0.78), a 61% reduction from a rate of 1.74 events/year at the time of enrollment. The mean (standard deviation [SD]) ACQ-5 score improved by 0.47 (0.99) points at the first post-baseline assessment (Week 12) and this was maintained until Week 228, with mean (SD) changes from baseline ranging from -0.40 (1.31) to -0.66 (1.22) over the treatment period. Improvements in mean pre-bronchodilator FEV1 were limited. There was an initial increase by 124 mL at Week 12 but this declined gradually over the study period back to approximately baseline values at Week 228. Geometric mean peripheral blood eosinophil counts were reduced by 78% from 240 cells/µL (standard logs 1.016) at baseline to 50 cells/µL (standard logs 0.951) at Week 4 and remained suppressed throughout the study period. Conclusions: COLUMBA is the first study to report on the long-term durability of pharmacodynamic and clinical responses following treatment with mepolizumab in patients with SEA for up to 4.5 years. These data support the long-term efficacy of mepolizumab in patients with SEA in terms of decreased exacerbations, improved asthma control, and reduced eosinophil count. Funding: GSK [MEA115666/NCT01691859]. Reference: [1] Pavord ID, et al. The Lancet 2012;380(9842):651-659