Head-to-head comparison of biologic efficacy in asthma: what have we learned?

We performed an in-depth appraisal of indirect head-to-head comparisons of biologics approved for asthma, including anti-IL5/5Rα (mepolizumab, benralizumab), anti-IL4Rα (dupilumab), anti-TSLP (tezepelumab) and anti-IgE (omalizumab), which was neither a systematic review nor a meta-analysis. A crude evaluation of 95% CI's for rate ratios which excluded unity revealed greater overall reductions in annualised exacerbations with dupilumab versus either mepolizumab or benralizumab and also with tezepelumab versus benralizumab. Furthermore in patients with eosinophils ≥ 300/μL exacerbation rates were lower for tezepelumab, dupilumab and mepolizumab versus benralizumab; and with eosinophils< 150/μL for tezepelumab versus dupilumab. For lung function, no overall differences in FEV1 response were observed between drugs where there was considerable heterogeneity of overlapping 95% CI's. Dupilumab was superior to benralizumab for oscillometry-derived peripheral lung resistance and compliance, as well as for attenuation of mannitol airway hyperresponsiveness. There were no differences in asthma control or quality of life scores where the effect sizes were small, along with wide overlaps in 95% CI's. There is an unmet need for prospective pragmatic randomised controlled trials to directly compare biologics, especially to assess clinical remission in both type 2 high and low asthma patients. Real-life studies might also evaluate complete remission with different biologics to include outcomes such as inhaled corticosteroid sparing, small airways dysfunction using oscillometry, abolition of airway hyperresponsiveness and to assess mucus plugging and remodelling as wall thickening with imaging.