Abstract:Objective To systematically evaluate the clinical efficacy and safety of intralymphatic immunotherapy (ILIT) for grass pollen-induced allergic rhinitis (AR).Methods Computer retrieval on electronic database from PubMed, Embase, Cochrane Library, CNKI and VIP were performed. Randomized clinical trials of ILIT in patients diagnosed with grass pollen-induced AR were included. Primary outcomes included symptoms score, medication score, combined symptoms and medication score and visual analog scale. Secondary outcomes included adverse events, quality of life, specific immunoglobulin E, specific immunoglobulin G4, skin prick test and nasal provocation test. Meta-analysis of symptom improvement was performed using RevMan 5.3 software.Results Nine trials included 269 participants were enrolled. All studies included grass pollen allergens and five also included grass and/or birch pollen allergens. The interval between injections was 4 weeks in all but one trial, which was 2 weeks. Compared to the placebo group, the ILIT group significantly improved the visual analog scale(P<0.05), whereas the symptom score, medication score, combined symptom and medication score, and the Juniper rhinoconjunctivitis quality-of-life questionnaire did not show statistically significant differences (all P>0.05), with the combined symptom and medication scores demonstrating moderate heterogeneity (I2=60%). An allergen injection every 4 weeks was the optimal interval to improve combined symptoms and medication score. Whether a booster injection or escalating dose improved clinical effect was inconclusive.Conclusion ILIT is generally safe and well-tolerated. Escalating dose may cause serious complications and should be performed with caution. ILIT may make a significant improvement on visual analog scale in grass pollen-induced AR. Larger and longer-term trials are needed to standardize treatment options. ILIT may play an important role in the future treatment of AR.