The safety of sublingual-swallow immunotherapy: an analysis of published studies
ABSTRACT As the main target of sublingual immunotherapy (SLIT) is to reduce at most the occurrence of adverse events (AE), safety represents a critical issue. This aspect deserves particular mention when a higher dose of allergen extract than traditional subcutaneous immunotherapy (SCIT) is required to be effective: that may be up to 500 times that employed for SCIT.
All published controlled studies concerning SLIT-swallow were analysed to evaluate AE rates.
Studies were subdivided in two groups: (i) studies using low allergen dose (LAD), i.e. ranging from 1 to 50 times the dose commonly administered with SCIT, and (ii) studies with high allergen dose (HAD), i.e. ranging from 50 to 500 times the dose administered with SCIT.
Twenty-five studies were altogether analysed: 13 studies belonged to the low-dose group, 12 belonged to the high-dose group. We considered all patients with at least one AE. Local reactions were significantly more frequent in the LAD group than in the HAD group (P<0.0001), while there was no difference in the rate of systemic reactions. Severe systemic reactions were never reported.
This study represents the first analysis of the safety of SLIT concerning the allergen dose employed in the treatment. There is evidence that AE occurrence is substantially not dose-dependent. This fact highlights two main clinical aspects: the elevated tolerability of SLIT in general and the safety of HAD regimen.
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ABSTRACT: Background Sublingual immunotherapy (SLIT) applied to type I respiratory allergies is commonly performed with natural allergen extracts. Herein, we developed a sublingual tablet made of pharmaceutical-grade recombinant Bet v 1.0101 (rBet v 1) and investigated its clinical safety and efficacy in birch-pollen allergic patients.Methods Following expression in E. coli and purification, rBet v 1 was characterized using chromatography, capillary electrophoresis, circular dichroism, mass spectrometry and crystallography. Safety and efficacy of rBet v 1 formulated as a sublingual tablet were assessed in a multi-centre, double-blind, placebo-controlled study conducted in 483 patients with birch pollen-induced rhinoconjunctivitis.ResultsIn-depth characterization confirmed the intact product structure and high purity of GMP-grade rBet v 1. The crystal structure resolved at 1.2 Å documented the natural conformation of the molecule. Native or oxidized forms of rBet v 1 did not induce the production of any proinflammatory cytokine by blood dendritic cells or mononuclear cells. Bet v 1 tablets were well tolerated by patients, consistent with the known safety profile of SLIT. The average adjusted symptom scores were significantly decreased relative to placebo in patients receiving once daily for 5 months rBet v 1 tablets, with a mean difference of 17.0-17.7% relative to the group treated with placebo (p<0.025), without any influence of the dose in the range (12.5 to 50 μg) tested.Conclusion Recombinant Bet v 1 has been produced as a well-characterized pharmaceutical-grade biological drug. Sublingual administration of rBet v 1 tablets is safe and efficacious in patients with birch pollen allergic rhinoconjunctivitis.This article is protected by copyright. All rights reserved.Allergy 04/2015; DOI:10.1111/all.12622 · 6.00 Impact Factor
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DESCRIPTION: Background: The worldwide increased prevalence of allergic diseases, and especially of respiratory allergy, is paralleled by increased health costs. This requires consideration of the cost to efficacy ratio of the available treatment to identify the optimal choice. Objective: To compare the different economic relevance, over a long evaluation time, of symptomatic pharmacologic therapy and sublingual immunotherapy (SLIT) in patients with allergic asthma. Methods: Seventy patients with perennial allergic asthma, sensitized to dust mites, were enrolled; 50 of these patients were treated with SLIT against house dust mites and 20 were treated with symptomatic drugs. The patients were evaluated for 2 years after discontinuing immunotherapy, which was performed for 3 years, to obtain a more complete follow-up. Symptom scores, medication scores, and all other direct medical costs were evaluated with a specific questionnaire. Results: Patients treated with SLIT plus drugs had a higher mean annual cost in the first year of SLIT treatment compared with patients only receiving drug treatment, but the mean annual cost became significantly lower since the end of SLIT both in the whole population and in the subgroups defined by disease severity. Conclusion: The economic advantage measured alongside this prospective observational study was long lasting and still present at the fifth year of the follow-up (2 years after discontinuing SLIT) and could positively be related to the persistent good clinical control of patients.
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ABSTRACT: Sublingual immunotherapy (SLIT) is increasingly used worldwide. Despite its safety being well ascertained, there is no universally accepted system to grade and classify its adverse events (AEs). According to the literature, it seems reasonable to classify and grade systemic side effects by using the previously published World Allergy Organization recommendations. On the other hand, local side effects are the most frequent with SLIT, sometimes leading to its discontinuation. Therefore grading of the severity of local side effects was perceived as necessary for the purpose of uniform reporting, classification, and quantification of this aspect. AWorld Allergy Organization Taskforce, after examining the available literature and the postmarketing surveillance data, proposed a clinically based grading of the severity of local AEs caused by SLIT. The use of the Medical Dictionary for Regulatory Activities nomenclature for AEs was also included in this context. The proposed grading system for SLIT-induced local reactions is expected to improve and harmonize surveillance and reporting of the safety of SLIT.The Journal of allergy and clinical immunology 07/2013; 132:93. · 11.25 Impact Factor