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

Shixian Liu,1– 4,* Jingyun Li,1,3,4,* Xu Zhang,2 Tingting Ma,5 Yan Liu,6 Yuan Zhang,2 Luo Zhang,1– 4 Chengshuo Wang1– 4 1Department of Otolaryngology Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Allergy, Beijing TongRen Hospital, Capital Medical University, Beijing, People’s Republic of China; 3Beijing Institute of Otolaryngology, Beijing Laboratory of Allergic Diseases, Beijing Key Laboratory of Nasal Diseases, Key Laboratory of Otolaryngology Head and Neck Surgery, Ministry of Education, Capital Medical University, Beijing, People’s Republic of China; 4Research Unit of Diagnosis and Treatment of Chronic Nasal Diseases, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 5Department of Allergy, Beijing Shijitan Hospital, Capital Medical University, Beijing, People’s Republic of China; 6Department of Otorhinolaryngology, Head and Neck Surgery, Peking University People’s Hospital, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chengshuo Wang, Department of Otolaryngology Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University, No. 17, Hougouhutong, DongCheng District, Beijing, 100005, People’s Republic of China, Tel +8610 58268375; +8613911623569, Fax +8610 85115988, Email [email protected] Luo Zhang, Department of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, No. 1, DongJiaoMinXiang, DongCheng District, Beijing, 100730, People’s Republic of China, Tel +8610 58265719; +86 13910830399, Fax +8610 85115988, Email [email protected]: 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