Efficacy and safety of mepolizumab in Korean patients with severe eosinophilic asthma from the DREAM and MENSA studies

Mi-Kyeong Kim, Hae-Sim Park, Choon-Sik Park, Soung-Jun Min, Frank C Albers, Steven W Yancey, Bhabita Mayer, Namhee Kwon, Mi-Kyeong Kim, Hae-Sim Park, Choon-Sik Park, Soung-Jun Min, Frank C Albers, Steven W Yancey, Bhabita Mayer, Namhee Kwon

Abstract

Background/aims: The efficacy and safety of mepolizumab in patients with severe eosinophilic asthma has been evaluated in a global clinical trial programme. This post hoc analysis assesses the efficacy and safety of mepolizumab in Korean patients.

Methods: Data from Korean patients in the Phase III, placebo-controlled, randomised DREAM (MEA112997/NCT01000506) and MENSA (MEA115588/ NCT01691521) studies were included. Patients ≥ 12 years old with severe eosinophilic asthma received mepolizumab (DREAM: 75, 250 or 750 mg intravenously [IV]; MENSA: 75 mg IV or 100 mg subcutaneously [SC]), or placebo every 4 weeks for 52 weeks (DREAM) or 32 weeks (MENSA). The primary outcome was the rate of clinically significant asthma exacerbations. Secondary outcomes included forced expiratory volume in 1 second (FEV1), Asthma Control Questionnaire (ACQ) and St George's Respiratory Questionnaire (SGRQ) scores (MENSA only). Blood eosinophil counts (BEC) and safety were assessed throughout.

Results: Reductions in the rate of clinically significant asthma exacerbations were observed with the approved (100 mg SC) and bioequivalent (75 mg IV) doses of mepolizumab in Korean patients who participated in DREAM and MENSA. In MENSA, trends for improvements from baseline at week 32 in pre-bronchodilator FEV1 (75 mg IV group), ACQ-5 and SGRQ scores (in both treatment groups) were seen versus placebo in Korean patients. Incidence of on-treatment adverse events was similar in Korean patients versus non-Korean patients as were observed reductions from baseline in BEC.

Conclusion: Mepolizumab treatment provided clinical benefits for Korean patients with severe eosinophilic asthma; the safety profile is consistent with the overall population.

Keywords: Asthma; Republic of Korea; Symptom flare up; Therapeutics.

Conflict of interest statement

Namhee Kwon, Soung-Jun Min, Frank C. Albers, Steven W. Yancey, and Bhabita Maye are employees of GSK and hold stocks/shares. Hae-Sim Park, Mi-Kyeong Kim, and Choon-Sik Park have no financial or other issues that might lead to conflict of interest.

Figures

Figure 1.
Figure 1.
Annual rate of clinically significant exacerbations with mepolizumab versus placebo in Korean patients. DREAM, Dose Ranging Efficacy And safety with Mepolizumab in severe asthma; MENSA, MEpolizumab as adjunctive therapy iN patients with Severe Asthma; CI, confidence interval; IV, intravenous; SC, subcutaneous.
Figure 2.
Figure 2.
Difference in change from baseline in pre-bronchodilator forced expiratory volume in 1 second (FEV1) with mepolizumab versus placebo in Korean patients from the MENSA (MEpolizumab as adjunctive therapy iN patients with Severe Asthma) study. Error bars show 95% confidence intervals. Patient numbers for each group were: mepolizumab 75 mg intravenous (IV); 15 (all time points); mepolizumab 100 mg subcutaneous (SC); 15 (all time points), and placebo; 15 (baseline, weeks 8 and 16) and 14 (at weeks 24 and 32). aBaseline mean ± SD pre-bronchodilator FEV1 mL were 1,859 ± 623, 1,771 ± 599, and 1,902 ± 550 in the 75 mg IV, 100 mg SC and placebo groups, respectively.
Figure 3.
Figure 3.
Difference in change from baseline in Asthma Control Questionnaire-5 (ACQ-5) score with mepolizumab versus placebo in Korean patients from the MENSA (MEpolizumab as adjunctive therapy iN patients with Severe Asthma) study. Error bars show 95% confidence intervals. Patient numbers for each group were: mepolizumab 75 mg intravenous (IV); 12 (baseline, weeks 8, 16 and 24), 11 (week 32); mepolizumab 100 mg subcutaneous (SC); 13 (baseline, weeks 8, 24 and 32), 12 (week 16), and placebo; 14 (baseline, weeks 8 and 16) and 13 (at weeks 24 and 32). aBaseline mean ± SD ACQ-5 scores were 1.6 ± 1.04, 1.1 ± 0.79, and 2.2 ± 1.2 for the 75 mg IV, 100 mg SC and placebo groups, respectively.
Figure 4.
Figure 4.
Ratio of change from baseline in blood eosinophil count with mepolizumab versus placebo in Korean patients from the MENSA (MEpolizumab as adjunctive therapy iN patients with Severe Asthma) study. Error bars show 95% confidence intervals. Patient numbers for each group were: mepolizumab 75 mg intravenous (IV); 15 (baseline, weeks 16, 24 and 32) and 13 (week 8); mepolizumab 100 mg subcutaneous (SC); 15 (all time points), and placebo; 15 (baseline) and 14 (weeks 8, 16, 24 and 32). aBaseline geometric mean ± SD logs blood eosinophil counts, in cells/μL, were 300 ± 0.82, 290 ± 1.05, and 240 ± 1.23 in the 75 mg IV, 100 mg SC and placebo groups, respectively.

References

    1. Yoo KH, Ahn HR, Park JK, et al. Burden of respiratory disease in Korea: an observational study on allergic rhinitis, asthma, COPD, and rhinosinusitis. Allergy Asthma Immunol Res. 2016;8:527–534.
    1. Chung KF, Wenzel SE, Brozek JL, et al. International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. Eur Respir J. 2014;43:343–373.
    1. O’Byrne PM, Naji N, Gauvreau GM. Severe asthma: future treatments. Clin Exp Allergy. 2012;42:706–711.
    1. Fajt ML, Wenzel SE. Development of new therapies for severe asthma. Allergy Asthma Immunol Res. 2017;9:3–14.
    1. Kim MH, Kim SH, Park SY, et al. Characteristics of adult severe refractory asthma in Korea analyzed from the severe asthma registry. Allergy Asthma Immunol Res. 2019;11:43–54.
    1. Wenzel SE. Asthma: defining of the persistent adult phenotypes. Lancet. 2006;368:804–813.
    1. ten Brinke A, Zwinderman AH, Sterk PJ, Rabe KF, Bel EH. “Refractory” eosinophilic airway inflammation in severe asthma: effect of parenteral corticosteroids. Am J Respir Crit Care Med. 2004;170:601–605.
    1. Yancey SW, Keene ON, Albers FC, et al. Biomarkers for severe eosinophilic asthma. J Allergy Clin Immunol. 2017;140:1509–1518.
    1. Nucala . Prescribing information [Internet] Research Triangle Park (NC): GlaxoSmithKline; c2019. [cited 2020 Feb 21]. Available from: .
    1. Ortega HG, Liu MC, Pavord ID, et al. Mepolizumab treatment in patients with severe eosinophilic asthma. N Engl J Med. 2014;371:1198–1207.
    1. Pavord ID, Korn S, Howarth P, et al. Mepolizumab for severe eosinophilic asthma (DREAM): a multicentre, double-blind, placebo-controlled trial. Lancet. 2012;380:651–659.
    1. Chupp GL, Bradford ES, Albers FC, et al. Efficacy of mepolizumab add-on therapy on health-related quality of life and markers of asthma control in severe eosinophilic asthma (MUSCA): a randomised, double-blind, placebo-controlled, parallel-group, multicentre, phase 3b trial. Lancet Respir Med. 2017;5:390–400.
    1. Chiba K, Yoshitsugu H, Kyosaka Y, et al. A comprehensive review of the pharmacokinetics of approved therapeutic monoclonal antibodies in Japan: are Japanese phase I studies still needed? J Clin Pharmacol. 2014;54:483–494.
    1. Ramamoorthy A, Pacanowski MA, Bull J, Zhang L. Racial/ethnic differences in drug disposition and response: review of recently approved drugs. Clin Pharmacol Ther. 2015;97:263–273.
    1. GSK . Clinical study report 2014 [Internet] Research Triangle Park (NC): GlaxoSmithKline; 2014. [cited 2020 Feb 21]. Available from: .
    1. Wechsler ME, Castro M, Lehman E, et al. Impact of race on asthma treatment failures in the asthma clinical research network. Am J Respir Crit Care Med. 2011;184:1247–1253.
    1. Baffi CW, Winnica DE, Holguin F. Asthma and obesity: mechanisms and clinical implications. Asthma Res Pract. 2015;1:1.
    1. WHO Expert Consultation Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies. Lancet. 2004;363:157–163.
    1. Shimoda T, Odajima H, Okamasa A, et al. Efficacy and safety of mepolizumab in Japanese patients with severe eosinophilic asthma. Allergol Int. 2017;66:445–451.
    1. Kurosawa M, Sutoh E. Prospective open-label study of 48-week subcutaneous administration of mepolizumab in Japanese patients with severe eosinophilic asthma. J Investig Allergol Clin Immunol. 2019;29:40–45.

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