Severe asthma outcomes over two years of therapy with mepolizumab

Abstract

Introduction: Mepolizumab is an anti-IL-5 biologic indicated for the long-term treatment of severe asthma. We have evaluated patient outcomes over the first 24-months of treatment.

Method: Data from patients continuing mepolizumab past yr 1 were included. Differences in clinical variables pre-treatment and after 1yr of therapy were compared between “sustained responders” (SR – those continuing to benefit at 24mo) and “late failures” (LF – treatment failure between 12 and 24 mo).

Results: 50 patients gave consent, median (IQR) age 52(45-61)yrs; 30% were LFs. In yr 2, SR had continued fall in prednisolone use [10(6-17.5)mg at baseline; 5(0-5.5)mg at 12 mo; 0(0-5)mg at 24 mo; p<0.001] but no additional improvements in ACQ or AQLQ vs 12 mo. Pre-treatment SR had lower blood eosinophils [0.42(0.35-0.55) vs 0.62(0.4-0.72), p=0.017] and better ACQ [2.75(1.85-3.92) vs 3.92(3.37-5.12), p=0.018] than LF. Over the first 12 mo both groups had improvement in AQLQ, blood eosinophils and prednisolone dose, but only SR improved exacerbation rate and ACQ. At 12 mo SR had better ACQ [2(0.82-3.41) vs 3(2.66-4.3) p=0.016] and AQLQ [4.67(3.8-6.2) vs 3.57(3.26-4.24) p=0.012] than LR.

Conclusions: 30% of patients with severe asthma who respond to mepolizumab over the first 12 mo of therapy subsequently fail in yr 2. In responders, further reductions in prednisolone dose can be achieved, but effects on ACQ and AQLQ appear to slow; these also may have less severe type II inflammation and better asthma control pre-treatment, and after 12 months show better asthma control, quality of life and fewer exacerbations than late failures. These factors merit further investigation as possible predictors of sustained response to mepolizumab.