The addition of mepolizumab to the standard of care significantly improved health-related quality of life measures and lung function compared with placebo in severe eosinophilic asthma, according to a study published recently in The Lancet Respiratory Medicine.1
Lead study investigator Professor Geoffrey Chupp, MD, from the Yale School of Medicine talked with Infectious Disease Advisor about the importance of the study. “Mepolizumab improves health-related quality of life (HRQoL) and in particular significantly improves symptoms within a month of starting treatment. This is the first trial of mepolizumab that examined HRQoL as the primary end point and shows that we can see improvements in symptoms rapidly with these drugs.”
Severe eosinophilic asthma frequently results in poor disease control and a rapid decline in lung function leading to a decrease in HRQoL.1 The St George’s Respiratory Questionnaire (SGRQ) was developed for patients with chronic airflow restriction,2,3 and evaluates symptoms, physical activity, and quality of life.
Mepolizumab, an anti-interleukin-5 monoclonal antibody, has shown significant reductions in exacerbation rates,4,5 dependency on oral corticosteroids,6 and significant improvements in the SGRQ4-6 as add-on therapy for severe eosinophilic asthma. However, the SGRQ was not measured as a primary end point4,6 and lung function improvement varied between studies.4,5 Therefore, the researchers performed a clinical trial (MUSCA) to evaluate quality of life with the SGRQ as a primary end point, lung function (forced expiratory volume 1 [FEV1], forced vital capacity [FVC], forced expiratory flow 25-75 [FEF25-75]) as secondary end points; and daily asthma symptom scores (Asthma Control Questionnaire (ACQ)-5) and exacerbations.
The MUSCA trial enrolled patients from 19 countries age 12 and older with severe eosinophilic asthma taking regular high-dose corticosteroids plus additional medication(s). Additional requirements included at least 2 exacerbations in the previous year and airflow obstruction indicated by FEV1.
Patients were randomly assigned to receive either a subcutaneous injection of mepolizumab 100 mg (n=274) or placebo (n=277) every 4 weeks in addition to standard care. The duration of the study was 24 weeks with SGRQ scores taken at baseline and at weeks 4, 12, 20, and 24. Spirometry, exacerbation reviews, and the ACQ-5 were taken at baseline and every 4 weeks.
The researchers found mepolizumab significantly improved the change in the SGRQ score from baseline to week 24 compared with placebo (−15.6 vs −7.9, treatment difference -7.7; 95% CI: −10.5 to −4.9; P <.0001). The minimal clinically important difference (MCID) was exceeded from week 12 onwards for mepolizumab compared with placebo.
Mean changes from baseline to week 24 in pre-bronchodilator FEV1 (treatment difference 120 ml; 95% CI: 47-192; P =.001), FVC (treatment difference 102 ml; 95% CI: 23-181; P =.012), and FEF25-75 (treatment difference 123 ml; 95% CI: 46-200; P =.002) were higher for mepolizumab compared to placebo.
The mean change in ACQ-5 scores from baseline to 24 weeks was greater in patients treated with mepolizumab compared with placebo (treatment difference −0.4; 95% CI: −0.6 to −0.2; P <.0001). In addition, more patients in the mepolizumab group had an MCID of 0.5 or higher at week 24 (59% vs 42%; P =.0014).
The mean yearly rates of clinically significant exacerbations and exacerbations requiring hospitalization or an emergency room visit were reduced in the treatment group compared with placebo by 58% (P <0.0001) and 68% (P =0.031), respectively. However, exacerbations requiring hospital admission alone were not significantly in either group.
No deaths occurred during the study and adverse events were similar in both the treatment and placebo groups.
- 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. doi:10.1016/S2213-2600(17)30125-X
- Sanjuás C, Alonso J, Prieto L, Ferrer M, Broquetas JM, Antó JM. Health-related quality of life in asthma: a comparison between the St George’s Respiratory Questionnaire and the Asthma Quality of Life Questionnaire. Qual Life Res. 2002;11:729-738.
- Jones PW, Quirk FH, Baveystock CM, Littlejohns P. A self-complete measure of health status for chronic airflow limitation. The St. George’s Respiratory Questionnaire. Am Rev Respir Dis. 1992;145:1321-1327.
- Orega HG, Liu MC, Pavord ID, et al; MENSA Investigators. Mepolizumab treatment in patients with severe eosinophilic asthma. N Engl J Med. 2014;371:1198-1207. doi:10.1056/NEJMoa1403290
- 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. doi:10.1016/S0140-6736(12)60988-X
- Bel EH, Wenzel SE, Thompson PJ, et al; SIRIUS Investigators. Oral glucocorticoid-sparing effect of mepolizumab in eosinophilic asthma. N Engl J Med. 2014;371:1189-1197. doi:10.1056/NEJMoa1403291