Intralymphatic immunotherapy (ILIT) versus standard care or placebo in allergic rhinitis: A systematic review and meta-analysis of randomized controlled trials

BACKGROUND: Subcutaneous immunotherapy (SCIT) is the gold standard for allergic rhinitis (AR) but is limited by long treatment duration and poor adherence. Intralymphatic immunotherapy (ILIT) has emerged as a time-efficient alternative. OBJECTIVE: To evaluate the efficacy and safety of ILIT compared with placebo or SCIT in patients with AR. METHODS: We searched PubMed, Scopus, Web of Science, Embase, and Cochrane CENTRAL up to February 2026 for randomized controlled trials (RCTs) comparing ILIT with placebo or SCIT. The primary outcome was the Combined Symptom and Medication Score (CSMS). Secondary outcomes included quality of life (RQLQ), symptom scores, and adverse events. Data were pooled using random-effects models. RESULTS: Sixteen RCTs involving 606 patients were included. ILIT significantly reduced CSMS compared with placebo (SMD = -0.51, 95% CI: -0.82 to -0.20, p < 0.001; MD = -1.32). However, no significant difference was observed in the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) scores (p = 0.74). In head-to-head comparisons with SCIT, ILIT showed similar efficacy at 3, 6, and 12 months for Total Symptom Score (TSS) and Total Nasal Symptom Score (TNSS). However, SCIT demonstrated superior durability at 24 and 36 months (p > 0.05 favoring SCIT trends). Regarding safety, ILIT was associated with a higher risk of local swelling compared with placebo (RR = 4.25, p < 0.001) but had a 58% lower risk of total adverse events compared with SCIT (RR = 0.42, p = 0.01). CONCLUSION: ILIT is an effective short-course alternative that reduces symptoms and medication use compared with placebo, though it may not significantly improve quality of life.