BACKGROUND: Allergic rhinoconjunctivitis is a global health problem. Different Allergen ImmunoTherapy (AIT) regimes are marketed but have low adherence because they are expensive, complex and time consuming. New AIT forms are needed.

OBJECTIVE: In a three-year follow-up double-blinded randomized placebo-controlled trial we aimed to investigate effect of intralymphatic AIT (ILIT).

METHODS: Patients with grass pollen rhinoconjunctivitis were treated with either three ILIT injections and an ILIT booster one year later, three ILIT injection and a placebo booster or three placebo injections and a placebo booster. Primary outcome was improvement in a combined symptom and medication score, cSMS. A novel evaluation tool with a linear regression model of cSMS and grass pollen counts was developed. Secondary outcomes were changes in grass specific immunoglobulins and skin and nasal provocation tests to grass pollen.

RESULTS: 36 patients were included. Log10 transformed cSMS was reduced by 0.30 (95%CI 0.11 - 0.49), p=0.002 equalling 48.5% (95%CI 24.5% - 62%), in the entirethree-year follow-up period, significant only in the first follow-up season but not in the second and third season. The regression model showed a 37%, p<0.001, reduction in cSMS. The booster injection had no additional. Secondary, repeated measures of IgE and IgG4 to grass, showed significant between-group difference and within-group change in the ILIT groups. No change in provocation test was found.

CONCLUSION: Intralymphatic immune therapy gives a substantial reduction in grass pollen allergy symptoms and use of rescue medication, significant in the first season after treatment. A booster injection had no additional effect.