Real-world application of a composite score to assess response to biologicals in childhood severe asthma

Background and objective: Real-world evidence for efficacy of biologics in children and young people (CYP) with severe asthma is limited. The CompOsite iNdex For Response in asthMa (CONFiRM) score is a recently developed composite response measure, ranging from non-response to super-response (−31to 69). Its utility in CYP has not been reported. We applied the CONFiRM score to a real-world population of children with severe asthma, compared it with the assessment of dedicated multidisciplinary team and tested potential baseline biomarkers predicting response. Methods: We undertook a single-centre, retrospective analysis of CYP with severe asthma treated with omalizumab or mepolizumab between 2008–2023. We analyzed response to treatment using two definitions: multidisciplinary team (MDT) decision (continue biologic or stop) and CONFiRM score (>11 defines response). Results: Sixty-eight children received omalizumab (median age 12.9 years, IQR 9.9–15.0), 32 mepolizumab (median age 12.9 years, IQR 10.8–14.6). Using the CONFiRM score, 82.6% responded to omalizumab and 61.5% to mepolizumab, compared to 80.7% to omalizumab and 92.6% to mepolizumab following MDT decision. CONFiRM score response had moderate agreement with MDT decision (kappa=0.589). CONFiRM responders to mepolizumab had significantly higher baseline blood eosinophils (median 0.88×10 9 cells·L −1 , IQR 0.81–1.15 versus median 0.20×10 9 cells·L −1 , IQR 0.13–0.82 p=0.006) and lower blood neutrophils (median 2.70×10 9 cells·L −1 , IQR 1.97–3.10 versus median 4.73 x10 9 cells·L −1 , IQR 3.86–6.10, p=0.005) than non-responders. Conclusion: The CONFiRM score was easy to use in a real-world setting and provided an objective composite measure of response to biologics in CYP. Baseline blood eosinophils and neutrophils correlated with CONFiRM score in patients treated with mepolizumab.