Abstract Rationale Monoclonal antibodies (“biologics”) are used to treat persistently uncontrolled moderate/severe asthma. There is limited data examining the effect of biologics on lung function in pediatric asthma, and those that do exist utilized race-based equations in their analysis. This retrospective analysis represents the first real-world study of the effect of biologics on lung function in pediatric asthma using race-neutral equations. Methods We examined data from 115 pediatric patients naïve to biologic therapy who started biologics between 2015-2025. Electronic health records were reviewed to obtain each patient’s height, weight, and spirometry results (FEV1, FVC, and FEV1/FVC) at each clinic visit one year before and after the first biologic dose was administered. Percent-of-predicted values were calculated using race-neutral GLI-Global reference equations. Medians of the percent-predicted FEV1, FVC, and FEV1/FVC for each biologic before and after initiation were used for analysis, and linear mixed-effects models were fit to determine the associations for each PFT for the biologics and their initiation phase. Results In our cohort (N = 115, mean age 11.4±3.4 years, 52% male, 62% Black), most patients were treated with dupilumab (n = 97), with smaller numbers receiving omalizumab (n = 13) or mepolizumab (n = 5). Average number of spirometry measurements prior to vs after biologic initiation was 3 (range 1-16) vs 4 (range 1-17). Demographic characteristics (age, sex, race) were similar between biologic agents. Dupilumab was associated with a significant improvement in FEV1, increasing from 86.4 ±1.8 percent-predicted before to 91.7 ±1.8 after biologic initiation (mean difference=5.31 95%CI=0.15-10.48, p = 0.044). Neither omalizumab nor mepolizumab were associated with statistically significant changes in FEV1, likely due to their small sample sizes. Data were thus combined to fit a linear mixed model adjusted for biologic prescribed: FEV1 was significantly higher post-initiation compared to prior (97.9 ±2.6 vs 92.5 ±3.0; mean difference=5.37 95%CI=0.26-10.48; p = 0.039). We found no statistically significant differences in FVC or FEV1/FVC. Conclusions To our knowledge, this is the first study showing that asthma biologics significantly improve FEV1 in pediatric asthma using GLI-Global race-neutral reference equations. Race-neutral reference equations are less likely to systematically underestimate asthma severity in Black patients, resulting in a more accurate assessment of biologic benefits. Further studies with larger sample sizes, additional biologics (including benralizumab and tezepelumab), and longer follow-up are needed to establish comparative benefits across agents. This abstract is funded by: Indiana Clinical and Translational Sciences Institute Grant UL1TR002529
Wu et al. (Fri,) studied this question.