Intralymphatic immunotherapy with tyrosine-adsorbed allergens: a double-blind, placebo-controlled trial

Abstract

Background Most previous studies used aluminum hydroxide-absorbed allergen extracts in evaluating the potential therapeutic roles of intralymphatic allergen-specific immunotherapy (ILAIT). In this study, we evaluated the therapeutic efficacy and safety of ILAIT with L-tyrosine-adsorbed allergen extracts of Dermatophagoides farinae, D. pteronyssinus, cat, dog, or mixtures thereof, in patients with allergic rhinitis induced by these allergens. Methods In this randomized, double-blind, placebo-controlled trial, study subjects received three intralymphatic injections of L-tyrosine-adsorbed allergen extracts (active group) or saline (placebo group) at 4-week intervals. Results Although ILAIT reduced daily medication use and skin reactivity to HDM and cat allergens at 4 months after treatment, overall symptom score on a visual analog scale (VAS), sinonasal outcome test-20 (SNOT-20), rhinoconjunctivitis quality of life questionnaire (RQLQ), daily symptom score (dSS), daily medication score (dMS), daily symptom medication score (dSMS), nasal reactivity to HDM allergen, and basophil activity to HDM, cat, and dog allergens at 4 months and 1 year after treatment were similar between the treatment and control groups. Intralymphatic injection was more painful than a venous puncture, and pain at the injection site was the most frequent local adverse event (12.8%); dyspnea and wheezing were the most common systemic adverse events (5.3%). Conclusions ILAIT with L-tyrosine-adsorbed allergen extracts does not exhibit profound therapeutic efficacy in allergic rhinitis and can provoke moderate-to-severe systemic reactions and cause pain at the injection site. Trial registration: clinicaltrials.gov: NCT02665754; date of registration: 28 January 2016

Recent Advances in Allergen-Specific Immunotherapy in Humans: A Systematic Review

“…With the exception of studies by Witten et al ( 23 ) and Park et al ( 43 ), in which ILIT was associated with negative results, ILIT has been widely reported to decrease reactivity to allergens in allergy skin tests and nasal allergen provocation tests, alleviate allergic symptoms, and reduce rescue medication use. These therapeutic effects have been observed within 4 months after treatment initiation ( 17 18 19 20 22 24 25 44 45 46 47 48 49 ).…”

“…Notably, meta-analyses have shown that ILIT significantly reduces CSMSs ( Fig. 2A ) ( 23 26 43 45 47 48 50 51 ). Regarding the negative results reported by Witten et al ( 23 ), Kündig et al ( 52 ), who first introduced ILIT for allergic diseases, suggested that a 2-week interval between intralymphatic injections may be insufficient.…”

“…Regarding the negative results reported by Witten et al ( 23 ), Kündig et al ( 52 ), who first introduced ILIT for allergic diseases, suggested that a 2-week interval between intralymphatic injections may be insufficient. However, a recent study also reported that symptoms, quality of life, and CSMSs did not differ between ILIT-treated and placebo groups, despite three intralymphatic allergen injections at 4-week intervals ( 43 ). This result is presumably because the target allergens were not grass or birch pollen allergens; instead, they were indoor inhalant allergens (e.g., house dust mites or pet dander), which were evaluated in only a few previous studies ( 17 25 46 49 ).…”

“…In addition to the target allergens and their preparations, there are several unsolved issues involved in establishing the optimal treatment protocols in ILIT. For example, it has not been determined whether gradual escalation ( 17 25 43 45 46 ) or fixation (in most studies) ( 18 19 22 23 24 44 47 48 ) of allergen doses is more effective during repeated intralymphatic injections. There is a need for further investigation regarding whether multiple allergens should be injected as a mixture into the same LN or separately into different LNs ( 20 25 29 43 46 ).…”

“…For example, it has not been determined whether gradual escalation ( 17 25 43 45 46 ) or fixation (in most studies) ( 18 19 22 23 24 44 47 48 ) of allergen doses is more effective during repeated intralymphatic injections. There is a need for further investigation regarding whether multiple allergens should be injected as a mixture into the same LN or separately into different LNs ( 20 25 29 43 46 ). Regarding the LN injection site, most studies have injected allergens into inguinal LNs, while one study used cervical LNs.…”