ATS 2021 will feature presentations of original research from accepted abstracts. Mini Symposia and Thematic Poster Sessions are abstract based sessions.
Please use the form below to browse scientific abstracts and case reports accepted for ATS 2021. Abstracts presented at the ATS 2021 will be published in the Online Abstract Issue of the American Journal of Respiratory and Critical Care Medicine, Volume 203, May 3, 2021.
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Previous Exacerbations Predict the Risk of Future Exacerbations After Stopping Versus Continuing Mepolizumab Treatment: Secondary Analysis of the COMET Trial
Session Title
TP10 - TP010 CLINICAL AND POPULATION-LEVEL STUDIES OF ASTHMA
Abstract
A1445 - Previous Exacerbations Predict the Risk of Future Exacerbations After Stopping Versus Continuing Mepolizumab Treatment: Secondary Analysis of the COMET Trial
Author Block: M. Humbert1, M. C. Liu2, W. C. Moore3, E. H. Bel4, N. Kaneko5, S. G. Smith6, N. Martin7, M. J. Gilson8, E. Mavropoulou9, R. G. Price10, S. Yancey6, O. Kornmann11; 1Université Paris-Saclay, Assistance Publique-Hôpitaux de Paris, Service de Pneumologie, Hôpital Bicêtre, Le Kremlin-Bicêtre, France, 2Divisions of Allergy and Clinical Immunology, Pulmonary and Critical Care Medicine, Johns Hopkins Asthma and Allergy Center, Baltimore, MD, United States, 3Department of Medicine, Wake Forest School of Medicine, Winston-Salem, NC, United States, 4Department of Respiratory Medicine, Amsterdam UMC, University of Amsterdam, Department of Respiratory Medicine, Amsterdam, Netherlands, 5Department of Pulmonary Medicine, Kameda Medical Center, Kamogawa, Japan, 6Respiratory Therapeutic Area, GSK, Research Triangle Park, NC, United States, 7Global Medical Affairs, GSK & Institute for Lung Health, University of Leicester, Brentford & Leicester, United Kingdom, 8Respiratory Research and Development, GSK, Uxbridge, United Kingdom, 9Clinical Statistics, GSK, Uxbridge, United Kingdom, 10Biostatistics, GSK, Stevenage, United Kingdom, 11IKF Pneumologie Frankfurt, Clinical Research Centre Respiratory Diseases, Frankfurt, Germany.
Rationale: To explore whether patient baseline characteristics can predict the outcome of stopping versus continuing long-term mepolizumab treatment in patients with severe eosinophilic asthma.
Methods: COMET (NCT02555371), was a randomized, double blind, placebo-controlled study in which 295 patients exposed to continuous mepolizumab treatment for ≥3years were randomized 1:1 to stop (switch to placebo) or continue mepolizumab treatment (100 mg SC every 4weeks) for 52 weeks. Post-hoc analysis was carried out to investigate the potential for baseline characteristics to predict the risk of clinically significant exacerbation in patients who stop versus continue mepolizumab. Baseline (at COMET randomization) characteristics of interest: exacerbations in the year prior (0, 1, ≥2), use of maintenance OCS (yes/no), blood eosinophil count (<50, 50-<150, ≥150 cells/µL), ACQ-5 score (<0.75, 0.75-<1.50, ≥1.50), presence of nasal polyps (yes/no), presence of sinusitis (yes/no). Subgroup analyses were performed using a Cox proportional hazard model adjusted for treatment group, region, baseline OCS use, and exacerbations in the year prior to randomization. Rosenkranz bootstrap model selection was performed to correct hazard ratios (HR) for selection bias.
Results: Number of exacerbations in the year prior to randomization was a strong prognostic factor for risk of exacerbation during the 52-week trial period, regardless of whether patients stopped or continued mepolizumab; patients with ≥2 exacerbations in the previous year (n=44) had a higher risk of exacerbation versus those with 0 (n=185) or 1 (n=66) exacerbation (Figure).
Stopping versus continuing mepolizumab increased the risk of first exacerbation by 74% (HR [95% CI]: 1.74 [1.08,2.80]) and 180% (2.80 [1.44,5.44]), respectively in patients who had 0 or 1 exacerbation in the previous year; however, this increased risk was not seen for patients with ≥2 exacerbations in the previous year (0.88 [0.46,1.67]). Heterogeneity in treatment effect was not identified in any further baseline characteristics assessed. Results in the subgroup of ≥2 prior exacerbations were similar when assessed using bias adjusted HR following Rosenkranz model selection.
Conclusions: Following ≥3years of mepolizumab treatment, the number of exacerbations in the year prior to COMET randomization was the strongest characteristic to predict future exacerbation risk. Patients who had few (≤1) prior exacerbations were at higher risk of exacerbation when stopping versus continuing mepolizumab, consistent with the primary findings of COMET. Patients with high (≥2) prior exacerbations had a similar exacerbation risk after stopping or continuing mepolizumab. Further analyses are required to understand the impact of discontinuing mepolizumab within these patients.
Funding: GSK(201810/NCT02555371)
Author Block: M. Humbert1, M. C. Liu2, W. C. Moore3, E. H. Bel4, N. Kaneko5, S. G. Smith6, N. Martin7, M. J. Gilson8, E. Mavropoulou9, R. G. Price10, S. Yancey6, O. Kornmann11; 1Université Paris-Saclay, Assistance Publique-Hôpitaux de Paris, Service de Pneumologie, Hôpital Bicêtre, Le Kremlin-Bicêtre, France, 2Divisions of Allergy and Clinical Immunology, Pulmonary and Critical Care Medicine, Johns Hopkins Asthma and Allergy Center, Baltimore, MD, United States, 3Department of Medicine, Wake Forest School of Medicine, Winston-Salem, NC, United States, 4Department of Respiratory Medicine, Amsterdam UMC, University of Amsterdam, Department of Respiratory Medicine, Amsterdam, Netherlands, 5Department of Pulmonary Medicine, Kameda Medical Center, Kamogawa, Japan, 6Respiratory Therapeutic Area, GSK, Research Triangle Park, NC, United States, 7Global Medical Affairs, GSK & Institute for Lung Health, University of Leicester, Brentford & Leicester, United Kingdom, 8Respiratory Research and Development, GSK, Uxbridge, United Kingdom, 9Clinical Statistics, GSK, Uxbridge, United Kingdom, 10Biostatistics, GSK, Stevenage, United Kingdom, 11IKF Pneumologie Frankfurt, Clinical Research Centre Respiratory Diseases, Frankfurt, Germany.
Rationale: To explore whether patient baseline characteristics can predict the outcome of stopping versus continuing long-term mepolizumab treatment in patients with severe eosinophilic asthma.
Methods: COMET (NCT02555371), was a randomized, double blind, placebo-controlled study in which 295 patients exposed to continuous mepolizumab treatment for ≥3years were randomized 1:1 to stop (switch to placebo) or continue mepolizumab treatment (100 mg SC every 4weeks) for 52 weeks. Post-hoc analysis was carried out to investigate the potential for baseline characteristics to predict the risk of clinically significant exacerbation in patients who stop versus continue mepolizumab. Baseline (at COMET randomization) characteristics of interest: exacerbations in the year prior (0, 1, ≥2), use of maintenance OCS (yes/no), blood eosinophil count (<50, 50-<150, ≥150 cells/µL), ACQ-5 score (<0.75, 0.75-<1.50, ≥1.50), presence of nasal polyps (yes/no), presence of sinusitis (yes/no). Subgroup analyses were performed using a Cox proportional hazard model adjusted for treatment group, region, baseline OCS use, and exacerbations in the year prior to randomization. Rosenkranz bootstrap model selection was performed to correct hazard ratios (HR) for selection bias.
Results: Number of exacerbations in the year prior to randomization was a strong prognostic factor for risk of exacerbation during the 52-week trial period, regardless of whether patients stopped or continued mepolizumab; patients with ≥2 exacerbations in the previous year (n=44) had a higher risk of exacerbation versus those with 0 (n=185) or 1 (n=66) exacerbation (Figure).
Stopping versus continuing mepolizumab increased the risk of first exacerbation by 74% (HR [95% CI]: 1.74 [1.08,2.80]) and 180% (2.80 [1.44,5.44]), respectively in patients who had 0 or 1 exacerbation in the previous year; however, this increased risk was not seen for patients with ≥2 exacerbations in the previous year (0.88 [0.46,1.67]). Heterogeneity in treatment effect was not identified in any further baseline characteristics assessed. Results in the subgroup of ≥2 prior exacerbations were similar when assessed using bias adjusted HR following Rosenkranz model selection.
Conclusions: Following ≥3years of mepolizumab treatment, the number of exacerbations in the year prior to COMET randomization was the strongest characteristic to predict future exacerbation risk. Patients who had few (≤1) prior exacerbations were at higher risk of exacerbation when stopping versus continuing mepolizumab, consistent with the primary findings of COMET. Patients with high (≥2) prior exacerbations had a similar exacerbation risk after stopping or continuing mepolizumab. Further analyses are required to understand the impact of discontinuing mepolizumab within these patients.
Funding: GSK(201810/NCT02555371)
