Intralymphatic immunotherapy of pollen-induced rhinoconjunctivitis: a double-blind placebo-controlled trial

Abstract

BackgroundAllergen-specific immunotherapy represents the only disease-modifying treatment for allergic diseases. We and others have previously demonstrated that intralymphatic immunotherapy (ILIT), a less time-consuming alternative to conventional subcutaneous immunotherapy (SCIT), is safe and effective. However, this has recently been disputed. The aim of this study was therefore to expand our previous trial, further assessing the safety and efficacy of ILIT.MethodsThirty-six patients with pollen-induced rhinoconjunctivitis were randomised to receive three intralymphatic inguinal injections of active allergen (1000 SQ-U birch- or grass-pollen) or placebo. Clinical effects, safety and circulating immunological markers were assessed before, 4 weeks after treatment and at the end of the consecutive pollen season.ResultsNo moderate or severe reactions were recorded following ILIT. Patients receiving active ILIT experienced a significant improvement in self-recorded seasonal allergic symptoms, as compared to placebo (p = 0.05). In a subgroup of these patients (“improved”), a reduction in nasal symptoms following nasal allergen provocation was also demonstrated. No changes in total IgE or IgG4 were found. However, the affinity of allergen specific IgG4 following active treatment was significantly increased, as compared to non-improved patients (p = 0.04). This could be correlated with clinical improvement, on an individual level.ConclusionsThis double-blinded placebo-controlled study confirms that ILIT is a safe and effective treatment for pollen-induced rhinoconjunctivitis, markedly reducing seasonal allergic symptoms.Trial registrationEudraCT: 2009-016815-39Electronic supplementary materialThe online version of this article (doi:10.1186/s12931-016-0324-9) contains supplementary material, which is available to authorized users.

A Pilot Study of Intralymphatic Immunotherapy for House Dust Mite, Cat, and Dog Allergies

“…In NAPTs, nasal reactivity to HDM allergens was decreased after ILIT as previously described 12356. Furthermore, the serum levels of allergen-specific IgE and IgG 4 to Df and Dp were increased 4 months after ILIT, being consistent with the results of previous studies 2314.…”

“…Like most previous studies of ILIT, the symptoms of AR and quality of life in this study were improved as early as 4 months after the first injection of ILIT, and lasted for 1 year 123456. In NAPTs, nasal reactivity to HDM allergens was decreased after ILIT as previously described 12356.…”

“…All previous studies of ILIT have reported that ILIT causes only mild adverse effects 1234567. However, we observed that ILIT could cause severe adverse reactions even at very low concentrations that were not expected to cause serious reactions in SCIT.…”

Intralymphatic Immunotherapy: Update and Unmet Needs

“…In 2016, Hylander et al [9] reported a double-blinded placebo-controlled clinical trial in 36 patients with birch- or grass pollen-induced rhinoconjunctivitis and concluded that ILIT is an effective and safe therapy for this condition, resulting in a marked reduction of seasonal allergic symptoms. In the same year Patterson et al [17] published a randomised, double-blind, placebo-controlled, parallel group pilot study in 15 adolescents in the USA with bothersome nasal, ocular, and/or respiratory symptoms correlating with the timing of the grass pollen season and evidence of grass pollen sensitisation.…”

“…The entire treatment is therefore finished after 2 months. In comparison, SCIT with common marketed allergen extracts requires up to 70 injections and visits to a medical practice over a time period of up to 5 years, something that only 5% of eligible patients judge worth the inconvenience [9]. ILIT poses a viable alternative to overcome the most urgent problem with long-term SCIT and SLIT management, oftentimes overlooked by the medical community, i.e., non-adherence to treatment [10].…”