Efficacy of Artemisia annua Sublingual Immunotherapy for Seasonal Allergic Rhinitis in Relation to Variable Pollen Exposure: A Multicenter Study

Purpose: Evaluating allergen immunotherapy efficacy amidst natural pollen fluctuations is complicated by pollen variation. This study evaluates the relationship between pollen exposure and therapeutic impact of Artemisia annua sublingual immunotherapy (SLIT) in seasonal allergic rhinitis (SAR). Patients and Methods: In a two-year multicenter, controlled trial, SAR patients sensitized to Artemisia received SLIT or symptomatic medication. Daily assessments of combined symptom and medication score (CSMS), total nasal symptom score (TNSS) and daily medication score (DMS), were conducted across two pollen seasons. Linear mixed-effect models (LMMs) were utilized to evaluate treatment effects while considering pollen variability. Exploratory analyses of immunoglobulins in serum and nasal secretions were performed. Results: Pollen fluctuations correlated positively with CSMS, TNSS, and DMS in both groups. SLIT significantly reduced the mean daily CSMS ( β = − 0.34, q < 0.001), TNSS ( β = − 1.01, q < 0.001), and DMS ( β = − 0.09, q < 0.001) compared to the control group. These effects were consistent across both pollen seasons. During the first pollen season, a significantly negative impact of group × time × pollen interactions on the average daily CSMS was observed in SLIT group ( β = − 0.11, P = 0.03). LMM analyses revealed significant group × time interactions for serum Artemisia -specific IgG4 and IgA with nasal IgA showing isolated significance. Conclusion: SLIT provided early and sustained symptom relief in SAR, taking into account the annual and seasonal pollen fluctuations. SLIT efficacy may be influenced by pollen exposure, with effect size increasing in correlation with higher levels of pollen exposure. SLIT elevated allergen-specific IgG4 and IgA in systemic and local compartments. Keywords: seasonal allergic rhinitis, sublingual immunotherapy, pollen exposure, symptom severity, efficacy