# Risk factors for drug resistance in allergen immunotherapy for allergic rhinitis: a systematic review and meta-analysis

## TL;DR

This study identifies risk factors that may lead to resistance in allergen immunotherapy for allergic rhinitis, including gender, immune markers, and clinical characteristics.

## Contribution

The study provides a comprehensive meta-analysis of risk factors for AIT resistance in allergic rhinitis patients.

## Key findings

- Male gender is associated with increased resistance to AIT (OR = 1.53).
- Immune markers like IL-10, IL-35, and TGF-beta are linked to resistance.
- Clinical factors such as disease severity and treatment adherence influence resistance.

## Abstract

Allergen Immunotherapy (AIT) is largely considered to be the only therapy that can provide relief from allergic rhinitis (AR).Although its effectiveness has been confirmed by the results of a large number of practical studies such as randomized controlled trials, it may in some cases have a poor or no response to treatment due to the development of resistance under the influence of certain risk factors. The purpose of this Meta-analysis was to examine the risk factors for AR resistance to AIT treatment.

A comprehensive literature search was conducted in PubMed, Embase, Web of Science, and Cochrane Library from inception to August 2025. Study quality was assessed using the NOS scale, AHRQ criteria, and the GRADE framework. Statistical analyses, performed with R 4.5.0 and Stata 14, employed fixed-or random-effects models to calculate pooled odds ratios (ORs) with 95% confidence intervals (CIs). Heterogeneity was explored via sensitivity analyses, and publication bias was evaluated using funnel plots with Begg and Egger tests.

A total of 12 studies involving 2,552 patients were included in this Meta-analysis. The results suggest that the following factors may be associated with AR resistance to treatment with AIT. Gender: male (OR = 1.53, 95% CI: 1.08–2.18); Specific diagnostic antibody aspects: s-IgE/t-IgE ratio (OR = 1.09, 95% CI: 1.02–1.16), sIgE, sIgG4; For cytokines: IL-10, IL-35, TGF-beta, IFN-gamma; On blood parameters: Eosinophil; Immune Cell Aspects:TH2/CD4, TFH2/CD4, CD23 + BNSM, CD23 + BSM, TFR/CD4, TFR/TFH2; Clinical/personal characteristics: demographics, disease severity, allergen type, treatment details, treatment adherence, symptom control, lung function, airway inflammation, inflammatory markers, immunologic markers, imaging markers, environmental and behavioral factors. With respect to the heterogeneity analysis, the heterogeneity of the other analyses was relatively low, except for age and t-IgE levels, where there was significant heterogeneity.

The risk of developing resistance to AIT treatment for AR is closely associated with patient factors including gender, antibodies, cytokines, hematological parameters, clinical/personal characteristics, immune cells, and other indicators.

PROSPERO CRD420251154551.