Rationale The Scottish Medicines Consortium provides advice to NHS boards and Area Drug and Therapeutics Committees across Scotland about the status of newly licensed medicines. In June 2016 positive advice was issued for mepolizumab, an anti-IL-5 mAb licensed for adult severe refractory eosinophilic asthma, for use in a restricted sub-population: patients who have eosinophils of ≥150 cells per microlitre (0.15 × 109/L) at initiation of treatment and had ≥4 asthma exacerbations in the preceding year or are receiving maintenance treatment with oral corticosteroids (mOCS). Here we present the results for this sub-population comparing the effect of mepolizumab with placebo in this subgroup.
Methods Three randomised, double-blind, placebo-controlled studies of mepolizumab in severe eosinophilic asthma were identified, which used the licensed 100 mg SC dose or the corresponding 75 mg IV dose of mepolizumab. For analysis purposes, these two treatment arms were combined. A post-hoc meta-analysis assessing the key outcome measures in the three phase IIb/III trials (DREAM [NCT01000506] and MENSA [NCT01691521] with a sensitivity analysis including SIRIUS [NCT01691508]) were run for the sub-population using individual patient data.
Results The post-hoc meta-analysis included 197 patients from DREAM and MENSA and 251 when including the SIRIUS trial. The mean age was 51.2 and 51.3 years of which 62% and 64% were female, respectively. A 59% (95% CI: 0.31, 0.55; p < 0.001) reduction in clinically significant exacerbations was seen in the meta-analysis of DREAM and MENSA (50% [95% CI: 0.40, 0.64, p < 0.001] sensitivity analysis with SIRIUS). The ACQ score showed an improvement of −0.56 (95% CI: −0.79,−0.33; p < 0.001) and −0.58 (95% CI: −0.79,−0.38; p < 0.001, sensitivity analysis with SIRIUS). The SGRQ was only used in MENSA and SIRIUS and showed an improvement in total score of −8.0 (−12.0, −3.9, p < 0.001).
Conclusion Mepolizumab treatment was effective in SMC advice population (adult severe refractory eosinophilic asthma patients with a blood eosinophil count of ≥150 cells/µL at initiation of treatment, and ≥4 exacerbations in the previous year or dependency on mOCS). The use of a post-hoc meta-analysis is a helpful approach to increase our understanding of mepolizumab’s treatment effect in the SMC restricted sub-population.