Mepolizumab improves QoL in severe eosinophilic asthma
Mepolizumab, a first-in-class anti-interleukin-5 immunotherapy approved in the US and Europe recently for severe eosinophilic asthma, has previously been shown to lower exacerbation rates, but its effect on HRQOL is less studied.
At week 24, mepolizumab-treated patients improved significantly in HRQOL, based on changes in the SGRQ** score from baseline compared with placebo controls (least square mean, -15.6 vs -7.9; p<0.0001). [Lancet Respir Med 2017;doi:10.1016/S2213-2600(17)30125-X]
Scores for the various SGRQ domains were also significantly improved from baseline in the mepolizumab vs the placebo groups (-21.1 vs -10.0 for symptom domain, -15.3 vs -8.0 for activity domain, and -13.9 vs -7.3 for impact domain; p<0.0001 for all).
“Improvements in SGRQ total score exceeded minimal clinically important difference [MCID] from week 12 onwards for mepolizumab vs placebo … which was sustained through to week 24,” said the researchers.
“The symptoms domain for the mepolizumab group had the earliest clear separation from placebo compared with the other domain scores, which suggests that the early improvements in the total score were driven mainly by the symptoms domain and the early and sustained improvements in lung function.”
Improvement in lung function at week 24 was higher with mepolizumab than with placebo, as indicated by mean changes in prebronchodilator FEV1#, FEF25-75##, and FVC### from baseline (treatment difference, 120; p=0.001, 123; p=0.002, and 102; p=0.012, respectively). In addition, lower rates of clinically significant exacerbations (0.51 vs 1.21; p<0.0001) were observed with mepolizumab vs placebo.
The researchers also assessed QoL with the Asthma Control Questionnaire (ACQ-5), which was significantly improved at week 24 from baseline in the mepolizumab vs the placebo groups (-0.8 vs -0.4; p<0.0001).
The on-treatment adverse event (AE) rates were comparable between the mepolizumab and placebo groups (70 percent vs 74 percent), with the most common AEs being headache (16 percent vs 21 percent) and nasopharyngitis (11 percent vs 17 percent). On-treatment serious AE occurred in 5 percent vs 8 percent of patients, with asthma being the most commonly reported in both groups (1 percent vs 3 percent).
The global, double-blind, phase IIIb trial enrolled 551 patients (aged ≥12 years) who had severe eosinophilic asthma and ≥2 exacerbations requiring treatment in the past 1 year despite regular use of controller medicines (including high-dose inhaled corticosteroids). They were randomized to subcutaneous mepolizumab 100 mg Q4W (n=274) and placebo (n=277) for 24 weeks.
An exploratory modelling suggests that the higher the blood eosinophil count at baseline, the greater the predicted effects of mepolizumab in improving ACQ-5 score, exacerbation rate, and prebronchodilator FEV1.
“These data support the blood eosinophil thresholds used to identify patients likely to benefit from treatment with mepolizumab,” observed the researchers.
“Identification of an early-response marker is an important priority because biological treatments are likely to be expensive, so healthcare payers will be keen for decisions about treatment efficacy to be made early,” wrote Dr Ian Pavord of Nuffield Department of Medicine in the University of Oxford, UK, in a separate commentary, adding that this, however, could be challenging due to potential confounding by placebo effects in the interpretation of post-treatment changes. [Lancet Respir Med 2017;doi:10.1016/S2213-2600(17)30132-7]
“Longer-term treatment goals could be set, and failure to achieve these should prompt a re-evaluation of the importance of that pathway and a consideration of alternative treatable biomarkers,” he suggested.