Intralymphatic immunotherapy for allergic rhinitis: A systematic review and meta-analysis

Background: Only a fraction of patients with allergic rhinitis receive allergen-specific immunotherapy (AIT). AIT is most commonly delivered subcutaneously in a series of injections over 3-5 years. Common obstacles to completing this therapy include cost and inconvenience. Intralymphatic immunotherapy (ILIT) has been proposed as a faster alternative, which requires as few as three injections spaced 4 weeks apart. Objective: This systematic review and meta-analysis evaluated the current evidence that supports the use of ILIT for allergic rhinitis. Methods: Clinical trials were identified in the published literature by using an electronic search strategy and were evaluated by using a risk of bias tool. Treatment outcome (symptom scores, medication scores, and combined symptom and medication scores) and provocation testing results (nasal provocation and skin-prick testing) were included in a meta-analysis of standardized mean difference with subgrouping by using a random-effects model. Overall adverse event rates were tabulated, and overall risk ratios were calculated by using a random-effects model. Results: We identified 17 clinical trials that met eligibility criteria. The standardized mean difference of ILIT on the symptom and medication score was -0.72 (95% confidence interval [CI], -0.98 to -0.46; p < 0.0001) (n = 10). The standardized mean difference of ILIT on nasal provocation and skin-prick testing was -1.00 (95% CI, -1.38 to -0.61; p < 0.0001) (n = 7) and -0.73 (95% CI, -0.99 to -0.47; p < 0.0001) (n = 7), respectively. No statistically significant heterogeneity was detected. The overall adverse event rate was 39.5% for ILIT and 23.5% for placebo. Also, 98.4% of adverse events were mild. Conclusion: Our meta-analysis demonstrated that ILIT was safe, conferred desensitization to seasonal and nonseasonal allergens, alleviated allergic rhinitis symptoms, and reduced medication use. A larger randomized, double-blind, placebo controlled trial will be necessary for wider adaptation of this form of AIT.