Age does not affect the efficacy of anti-IL-5/IL-5R in severe asthmatics

摘要

Background: Healthcare decisions made on the basis of insufficient evidence may potentially have ineffective or even harmful consequences. The proportion of older ages (over 65 years) in randomized controlled trials (RCTs) for severe asthma is not enough to establish whether anti-IL-5/IL-5R therapies are equally effective in the elderly as in younger subjects. Methods: In order to assess the relationship between age and the efficacy of anti-IL-5 monoclonal antibodies (mABs) with respect to the risk of exacerbations and changes in FEV1, a meta-regression analysis via random-effect method was carried out by plotting the effect estimates (outcome variables) resulting from the pairwise meta-analysis with the age of asthmatic subjects (explanatory variable). A comprehensive literature search was performed for pivotal RCTs on the effects of anti-IL-5/IL-5R in severe asthma, with the following keywords: “asthma and mepolizumab”, “asthma and reslizumab” and “asthma and benralizumab”. The study was restricted to “clinical trials”, “age over 65” and “humans”. Data were checked for age, exacerbation rates, changes from baseline in FEV1, and blood eosinophil (Eos) count. Secondary outcomes included inhaled and oral medication use, clinical scores and quality of life. Results: A total of 10 studies were analysed. Age did not modulate the efficacy of anti-IL-5/IL-5R treatment against the risk of exacerbation neither in the overall population (coefficient −0.007, P = 0.89), nor in patients with high blood Eos count (coefficient 0.075, P = 0.30). The blood Eos level drove the efficacy of anti-IL-5/IL-5R mABs against the risk of exacerbation regardless of age (coefficient −0.27, P < 0.001). Age did not significantly affect the efficacy of anti-IL-5/IL-5R mABs with respect to the change in FEV1 (coefficient −7.15, P = 0.190); however, in high Eos subjects this improvement tended to be less evident in the more advanced age ranges (coefficient −15.18, P = 0.087). In addition, anti-IL-5/IL-5R mABs reduced ACQ score (P < 0.001 vs. placebo), SGRQ score (P < 0.001 vs. placebo), Total Asthma Symptom Score (P < 0.05 vs. placebo), and the use of oral glucocorticoids (P < 0.001 vs. placebo). Conclusions: Age does not negatively affect the efficacy of anti-IL-5/IL-5R mABs. These findings support the use of anti-IL-5/IL-5R mABs in asthmatics of different age ranges. Keywords: Severe asthma, Age, Anti-IL5, Therapy, Eosinophils