Reappraisal of Biologic Efficacy from Phase 3 Trials in Refractory Chronic Rhinosinusitis and Nasal Polyps

Chronic rhinosinusitis with nasal polyps (CRSwNP) is commonly associated with type 2 inflammation and may be punctuated by exacerbations requiring systemic corticosteroids and eventually a need for surgery. The use of biologics to target type 2 inflammation has greatly ameliorated the management of refractory CRSwNP. Currently available biologics act upstream by blocking the epithelial cytokine thymic stromal lymphopoietin (TSLP) or downstream blocking type 2 cytokines including Interleukin (IL4), IL5, and IL13, or Immunoglogulin E (IgE). Synthesizing the data from phase 3 randomized control trials using Forest plots to compare crude 95% confidence intervals permits an indirect comparison of different biologics in terms of their relative efficacy. Anti-TSLP (tezepelumab) or anti-IL4Rα (dupilumab) provide the best improvements in coprimary end points of nasal polyp and congestion score compared with other biologics including anti-IL5/5Rα (mepolizumab, depemokimab, and benralizumab) and anti-IgE (omalizumab). Greater improvements were also seen with tezepelumab and dupilumab in regard to olfaction as loss of smell score and University of Pennsylvania Smell Identification Test, computerized tomography sinus imaging as Lund Mackay score, and also the need for surgery or rescue use of systemic corticosteroid. Prospective pragmatic studies are required to directly compare different biologics in type 2 high and low CRSwNP, including effects on the unified airway in patients with severe asthma and CRSwNP, in particular to look at quality of life as well as clinical remission for upper and lower airway outcomes.