Distinct treatment response trajectories to allergen immunotherapy in allergic asthma and rhinitis: Insights from a multicenter study in routine clinical practice.

Background: While allergen-specific immunotherapy (AIT) is recognized as an effective treatment, its efficacy varies widely. However, whether clinical response trajectories to AIT differ among individuals and influence its effectiveness has not been investigated. Objective: This study aimed to characterize real-world clinical response trajectories to three-year AIT (3y-AIT). Methods: We conducted a retrospective multicenter study across 53 centers to identify clinical response trajectories in patients with house dust mite allergic asthma and rhinitis undergoing three-year AIT. The efficacy of AIT was primarily assessed using the Visual Analog Scale (VAS) for allergic symptoms at 4 time points: baseline (before AIT), and at 1, 2, and 3 years of treatment. Clustering analysis based on VAS changes at these time points was used to define response trajectories. Initial analysis was performed using data from 52 centers (Alliance cohort), and validation was conducted using data from a separate center (Guangzhou cohort). Results: In the Alliance cohort, 4 distinct clinical response trajectories were identified. Cluster 1 showed symptom worsening in the first year, with no improvement by year 3. Cluster 2 exhibited symptom deterioration in the second year, followed by significant recovery and a positive response by year 3. Clusters 3 and 4, characterized by higher and lower baseline symptom severity, respectively, demonstrated marked improvement after 3 years of AIT. In the Guangzhou cohort, a similar pattern of 4 response trajectories was observed: higher baseline symptom severity and family tobacco exposure were key features of Cluster 1 (p < 0.001), while Cluster 2 had the highest rate of respiratory infections (>1/year, p < 0.001). Despite these distinct trajectories, first-year effectiveness emerged as an ideal predictor of the 3-year AIT response, with an AUC of 0.75. Conclusion: This study identified 4 primary treatment response trajectories to 3-year AIT in daily clinical practice, highlighting the heterogeneous nature of AIT responses among individuals. Notably, first-year effectiveness appears to be an ideal predictor of the 3-year AIT outcome.