High‐dose pollen intralymphatic immunotherapy: Two RDBPC trials question the benefit of dose increase

Abstract

Background:The same dosing schedule, 1000 SQ-U times three, with one-month intervals, have been evaluated in most trials of intralymphatic immunotherapy (ILIT) for the treatment of allergic rhinitis (AR). The present studies evaluated if a dose escalation in ILIT can enhance the clinical and immunological effects, without compromising safety.Methods: Two randomized double-blind placebo-controlled trials of ILIT for grass pollen-induced AR were performed. The first included 29 patients that had recently ended 3 years of SCIT and the second contained 39 not previously vaccinated patients. An up-dosage of 1000-3000-10,000 (5000 + 5000 with 30 minutes apart) SQ-U with 1 month in between was evaluated.Results: Doses up to 10,000 SQ-U were safe after recent SCIT. The combined symptom-medication scores (CSMS) were reduced by 31% and the grass-specific IgG4 levels in blood were doubled. In ILIT de novo, the two first patients that received active treatment developed serious adverse reactions at 5000 SQ-U. A modified up-dosing schedule; 1000-3000-3000 SQ-U appeared to be safe but failed to improve the CSMS. Flow cytometry analyses showed increased activation of lymph

Update on pathomechanisms and treatments in allergic rhinitis

“…ILIT involves injecting allergen extracts into a subcutaneous lymph node under ultrasound guidance and has been assessed in several recent studies. [106][107][108] Intra-lymph node injections of modular allergen translocation (MAT)-Fel d 1 vaccine (a major category of allergens) has been shown to induce allergen tolerance and promote cellular internalization of the allergen, inflammasome activation, and allergenspecific peripheral T-cell tolerance development. 109 However, this allergen preparation is still under investigation.…”

“…110 In contrast, ILIT using tyrosine-adsorbed allergen extracts provided no profound therapeutic effects on AR symptoms induced by HDM, cat, or dog allergens. 111 It is noteworthy, however, that allergens may leak out of lymph nodes during injection 107 and drain rapidly into the venous system, possibly leading to adverse reactions. 112 Considering the comparatively small number of patients recruited for ILIT, the efficacy and potential adverse events of this form of therapy still need to be confirmed.…”

Strengthening the case for intralymphatic immunotherapy

“…Most clinical trials were performed with commercially available medicine. One unsuccessful trial was performed with house dust mite, cat, or dog allergoids from Allergy Therapeutics LTD (Worthing, UK) [16] stabilized with microcrystalline tyrosine, and successful trials were performed with house dust mite allergoids from Allergopharma (Hamburg, DE) stabilized with glycerin [11] and with bee venom, grass and birch Alutard from ALK Abe ´llo ´(Hørsholm, DK) stabilized with aluminium hydroxide [4,5,12 && , 18,19,24]. One historic trial reported on early attempts to use a bee venom extract presently not registered [5].…”

“…The most recent publication in [2] was Hellkvist et al [3]. Two publications presented more than one small, separate trial [4,5]. This unfortunate trend dilutes the impact of the individual trial.…”

Epidemiology, Prevention and Clinical Treatment of Allergic Rhinitis: More Understanding, Better Patient Care

“…It is hoped that advances in immunotherapy technology will achieve greater efficacy and safety. AIT administration routes, adjunctive therapies, vaccine adjuvants and novel vaccine technologies are being pursued to achieve this goal [ 24 , 25 , 26 ]. Intra-lymphatic immunotherapy, component-resolved AIT, recombinant proteins, nanoparticles and virus-like particle vaccines, T- and B-cell peptides and allergoids are potential options to improve AIT effectiveness and reduce side effects.…”