PURPOSE: Patients with seasonal allergic rhinitis (SAR) usually seek treatment when symptoms become unbearable during the pollen season. It remains unclear whether initiating sublingual immunotherapy (SLIT) during the pollen season affects patients' safety. This study aims to compare the tolerability of initiating Artemisia annua SLIT during the pollen season versus before the season. METHODS: Ninety patients with Artemisia-induced SAR were recruited and equally randomized into the coseasonal initiation treatment (COS-SLIT) group and the preseasonal initiation treatment (PRE-SLIT) group. The COS-SLIT group started SLIT when allergic symptoms occurred during the 2022 pollen season, while the PRE-SLIT group began SLIT four months before the expected season in 2022. Patients were categorized as mild symptoms or moderate-severe symptoms group based on the level of visual analog scale (VAS) scores evaluated during the 2021 pollen season. The incidence, frequency, performance, and alleviating measures of adverse events (AEs) were analyzed after the up-dosing phase (5 weeks), at three months (13 weeks), six months (26 weeks), and twelve months (52 weeks). RESULTS: A total of 72 patients (32 patients in the COS-SLIT group and 40 patients in the PRE-SLIT) were included in the analysis. Among these patients, 33 reported a total of 78 AEs. No significant difference was found in the frequency and number of patients experiencing AEs between the COS-SLIT and PRE-SLIT groups during the four follow-up periods (all p >
0.05). There were no significant differences in the symptoms or alleviating measures of AEs between the two groups in general (all p >
0.05). Furthermore, the most common AEs in the COS-SLIT group were nasal symptoms (n = 14), lip edema (n = 10), and cough (n = 4), while in the PRE-SLIT group were nasal symptoms (n = 12), lip edema (n = 8), and ocular pruritus (n = 6). Symptomatic drugs were the most common alleviating measures in both groups (61.29% in COS-SLIT and 64.52% in PRE-SLIT, p >
0.05). Patients with mild and moderate-severe symptoms showed comparable tolerability at different initiation timing (all p >
0.05). CONCLUSION: This prospective study demonstrates the comparable safety and tolerability of initiating Artemisia annua SLIT during the pollen season and before the season.