Sublingual immunotherapy for allergic rhinitis: systematic review and meta‐analysis*

Abstract

Allergic rhinitis is a common condition which, at its most severe, can significantly impair quality of life despite optimal treatment with antihistamines and topical nasal corticosteroids. Allergen injection immunotherapy significantly reduces symptoms and medication requirements in allergic rhinitis but its use is limited by the possibility of severe systemic reactions. There has therefore been considerable interest in alternative routes for delivery of allergen immunotherapy, particularly the sublingual route. The objective was to evaluate the efficacy of sublingual immunotherapy (SLIT), compared with placebo, for reductions in symptoms and medication requirements. The Cochrane Controlled Clinical Trials Register, MEDLINE (1966MEDLINE ( -2002, EMBASE (1974EMBASE ( -2002 and Scisearch were searched, up to September 2002, using the terms (Rhin* OR hay fever) AND (immunotherap* OR desensiti*ation) AND (sublingual). All studies identified by the searches were assessed by the reviewers to identify Randomized Controlled Trials involving participants with symptoms of allergic rhinitis and proven allergen sensitivity, treated with SLIT or corresponding placebo. Data from identified studies was abstracted onto a standard extraction sheet and subsequently entered into RevMan 4.1. Analysis was performed by the method of standardized mean differences (SMD) using a random effects model. i>P-values < 0.05 were considered statistically significant. Subgroup analyses were performed according to the type of allergen administered, the age of participants and the duration of treatment. Twenty-two trials involving 979 patients, were included. There were six trials of SLIT for house dust mite allergy, five for grass pollen, five for parietaria, two for olive and one each for, ragweed, cat, tree and cupressus. Five studies enrolled exclusively children. Seventeen studies administered the allergen by sublingual drops subsequently swallowed, three by drops subsequently spat out and two by sublingual tablets. Eight studies involved treatment for less than 6 months, 10 studies for 6-12 months and four studies for greater than 12 months. All included studies were double-blind placebo-controlled trials of parallell group design. Concealment of treatment allocation was considered adequate in all studies and the use of identical placebo preparations was almost universal. There was significant heterogeneity, most likely due to widely differing scoring systems between studies, for most comparisons. Overall there was a significant reduction in both symptoms (SMD )0.42, 95% confidence interval )0.69 to )0.15; P ¼ 0.002) and medication requirements [SMD )0.43 ()0.63, )0.23); P ¼ 0.00003] following immunotherapy. Subgroup analyses failed to identify a disproportionate benefit of treatment according to the allergen administered. There was no significant reduction in symptoms and medication scores in those studies involving only children but total numbers of participants was too small to make this a reliable conclusion. Increasing duration of trea...

Strategies of mucosal immunotherapy for allergic diseases

“…Comparisons of skin biopsies from the subcutaneous injection sites 142 and the oral mucosa 143 of SLIT-treated allergic subjects confirmed the negligible presence of inflammatory cells. 144 In addition, the high doses administered with oral immunotherapy resulted in significant local reactions, including gastrointestinal bleeding, which were possibly able to interfere with antigen absorption and thus with immunization.…”

“…145 Clinically, use of the sublingual route is supported by numerous controlled trials showing its efficacy in asthma and rhinitis in adults and children. 143,146 Additionally, no severe adverse events occurred during the trial, and the most common adverse events were mild asthma attack and local rash. Cao et al evaluated the safety and efficacy of SLIT with Der f drops in Der f allergic asthma and/or rhinitis patients.…”

Recommendations for appropriate sublingual immunotherapy clinical trials

“…It is clear, looking at the published articles that SLIT is clinically effective [7]. It is also clear that there is a large heterogeneity among studies, mainly due to the variability in the inclusion criteria, dose of allergen, duration, methodological aspects, and reporting.…”

“…Some studies have clearly shown a dose-dependent effect of SLIT [5,6], indicating robust support in favor of its clinical efficacy. Due to the large number of trials available, several meta-analyses have been carried out (Table 1), with various inclusion criteria such as rhinitis and asthma [7,8], asthma only [9], asthma and/or rhinitis in children [10,11], conjunctivitis [12]. Moreover, separate meta-analyses for single allergens such as dust mite [13] or grasses [14] have also been published, with favorable results as well.…”

Towards evidence‐based medicine in specific grass pollen immunotherapy

“…We evaluated the nature, quantity and quality of research evidence (essentially efficacy and safety) and patient values [quality of life (QoL) and treatment satisfaction] in DBPC RCTs. We did not seek to define the efficacy and safety of SIT itself or directly compare SCIT and SLIT, because these topics have been examined and discussed elsewhere (9)(10)(11)(12)(13)(14).…”