Mepolizumab in patients ≥3 exacerbations and eosinophil count ≥300 cells/µL

Rationale: The PH3 mepolizumab (mepo) MENSA (M) study included patients (pt) with a history of ≥2 exacerbations in the year (yr) preceding randomization, receiving high dose ICS + ≥1 additional asthma controller, and blood eosinophils (eos) ≥300 cells/µL in the past yr or ≥150 cells/µL immediately prior to treatment. Recently, there has been interest in the sub-group of patients with a history of ≥3 exacerbations in the past yr and ≥300 cells/µL at baseline (sub-pop). Methods: This post-hoc analysis was conducted using a negative binomial regression model. The 100mg SC and the 75mg IV dose groups were combined for analysis. Results: In M, 191 and 385 pt received placebo (pbo) or mepo respectively, compared with 61 and 128 in the sub-pop. The exac rate/yr in M was 1.74 and 0.88 in pbo and mepo respectively, compared with 2.62 and 0.89 in the sub-pop. The rate ratio mepo v pbo (95% CI), was 0.50 (0.39 0.65), a 50% reduction for mepo pt, and 0.34 (0.23 0.51), a 66% reduction in the sub-pop. The ED/hospitalization rate/yr in M was 0.20 and 0.11 in pbo and mepo respectively, compared with 0.41 and 0.18 in the sub-pop. The rate ratio mepo v pbo (95% CI) was 0.52 (0.28 0.96), a 48% reduction for mepo pt, and 0.43 (0.17 1.07), a 57% reduction in the sub-pop. Mepo was well tolerated in the sub-pop with a safety profile similar to pbo and comparable to the M profile. Discussion: These results show increased efficacy of mepo in a sub-population with greater morbidity as compared with the overall M population. This observation is not unexpected as it has been previously reported that blood eos counts and exac history are positively correlated with treatment benefit with mepo. (Funding GSK: NCT01691521).