Head-To-Head Comparison of Biologic Efficacy in Asthma: What Have We Learned?

Abstract

ABSTRACTWe 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), whichwas neither a systematic review nor a meta-analysis. A crude evaluation of 95% CI's for rate ratios which excluded unity revealedgreater overall reductions in annualised exacerbations with dupilumab versus either mepolizumab or benralizumab and alsowith tezepelumab versus benralizumab. Furthermore in patients with eosinophils ≥ 300/μL exacerbation rates were lower fortezepelumab, dupilumab and mepolizumab versus benralizumab; and with eosinophils< 150/μL for tezepelumab versus dupi-lumab. For lung function, no overall differences in FEV1 response were observed between drugs where there was considerableheterogeneity of overlapping 95% CI's. Dupilumab was superior to benralizumab for oscillometry- derived peripheral lung resist-ance and compliance, as well as for attenuation of mannitol airway hyperresponsiveness. There were no differences in asthmacontrol or quality of life scores where the effect sizes were small, along with wide overlaps in 95% CI's. There is an unmet need forprospective pragmatic randomised controlled trials to directly compare biologics, especially to assess clinical remission in bothtype 2 high and low asthma patients. Real-life studies might also evaluate complete remission with different biologics to includeoutcomes such as inhaled corticosteroid sparing, small airways dysfunction using oscillometry, abolition of airway hyperrespon-siveness and to assess mucus plugging and remodelling as wall thickening with imaging 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), whichwas neither a systematic review nor a meta-analysis. A crude evaluation of 95% CI's for rate ratios which excluded unity revealedgreater overall reductions in annualised exacerbations with dupilumab versus either mepolizumab or benralizumab and alsowith tezepelumab versus benralizumab. Furthermore in patients with eosinophils ≥ 300/μL exacerbation rates were lower fortezepelumab, dupilumab and mepolizumab versus benralizumab; and with eosinophils< 150/μL for tezepelumab versus dupi-lumab. For lung function, no overall differences in FEV1 response were observed between drugs where there was considerableheterogeneity of overlapping 95% CI's. Dupilumab was superior to benralizumab for oscillometry- derived peripheral lung resist-ance and compliance, as well as for attenuation of mannitol airway hyperresponsiveness. There were no differences in asthmacontrol or quality of life scores where the effect sizes were small, along with wide overlaps in 95% CI's. There is an unmet need forprospective pragmatic randomised controlled trials to directly compare biologics, especially to assess clinical remission in bothtype 2 high and low asthma patients. Real-life studies might also evaluate complete remission with different biologics to includeoutcomes such as inhaled corticosteroid sparing, small airways dysfunction using oscillometry, abolition of airway hyperrespon-siveness and to assess mucus plugging and remodelling as wall thickening with imaging