Patients with Higher Exacerbation Burden and Eosinophil Counts are More Likely to Require Multiple Biologics for Asthma Control.

Background: Multiple biologics are now available for severe asthma, creating opportunities to switch between therapies. Purpose: To identify characteristics of patients with asthma who switch biologics. Methods: We examined biologic switching in 1611 patients with moderate-to-severe asthma on maintenance therapy who initiated a biologic between 2014 and 2023 within a large health system and had no alternate indication. Chart reviews were performed to determine reasons for switching. We compared the characteristics of patients who: 1) did not switch therapy versus switched due to suboptimal response, and 2) switched once versus switched multiple times using descriptive statistics. Exacerbation incidence rates were assessed using Poisson regression. Inverse-probability-weighted-logistic regression accounting for demographic and clinical variables was conducted to evaluate factors associated with switching. Results: Fourteen percent (230/1611) switched: 81% once, 19% ≥2 times. Suboptimal response accounted for >70% of switches. Higher pre-initiation exacerbation rates were associated with a stepwise increase in likelihood of switching (1.4 in non-switchers vs 2.3 in patients who switched twice; 2.8 switched twice; and 3.4 in patients switching ≥3 times). Patients using ≥3 biologics had more baseline exacerbations (2.9 vs 2.3 in one-time switchers, p=0.01) and higher maximum blood eosinophil counts (BEC) in the year prior to treatment (662 vs 334 cells/µL, p=0.02), though median baseline BEC did not differ (229 vs 244 cells/µL, p=0.60). In weighted analyses, exacerbations (odds ratio, OR: 1.03; 95% Confidence Intervals, CI: 1.01-1.04, p<0.001) and baseline BEC (OR, 2.0 for each 50 cells/mcl increase; 95% CI: 1.2-3.4, p=0.002) were significantly different between switchers and non-switchers. However, only higher baseline exacerbations differentiated those who switched once to those who switched two or more times (1.02, 1.00-1.05, p=0.04). Exacerbations declined significantly in non-switchers during the first treatment year (1.42 to 0.99, p<0.001) but not among switchers. Conclusion: Patients with more severe asthma and higher maximum eosinophil counts at biologic initiation were more likely to switch therapies, predominantly due to suboptimal response. These findings emphasize the importance of selecting the first biologic carefully and optimizing timing of initiation.