Sublingual Immunotherapy May Be Safe, Effective for Allergic Rhinitis

Sublingual immunotherapy may be safe and effective for allergic rhinitis, according to an updated review reported online December 8 in the Cochrane Database of Systematic Reviews. The previous systematic review on this topic was first published in The Cochrane Database System Reviews.

“Allergic rhinitis is a common condition which can significantly impair quality of life,” write Suzana Radulovic, from the LEAP Study Team, Paediatric Allergy Research Department in London, United Kingdom, and colleagues. “Immunotherapy by injection can significantly reduce symptoms and medication use but its use is limited by the possibility of severe systemic adverse reactions. Immunotherapy by the sublingual route is therefore of considerable interest.”

The goal of this systematic review was to assess the effectiveness and safety of sublingual immunotherapy for allergic rhinitis. Through August 14, 2009, the reviewers searched the Cochrane ENT Group Trials Register; CENTRAL (2010, Issue 3); PubMed; EMBASE; CINAHL; Web of Science; BIOSIS Previews; Cambridge Scientific Abstracts; mRCT; and other sources for published and unpublished randomized, double-blind, placebo-controlled trials of sublingual immunotherapy in adults and children. Other criteria for studies to be included in the review were use of symptom and medication scores in adults or children, and reporting of adverse event data.

Studies were selected by 2 independent authors, who also examined the risk for bias. Data were extracted by 1 reviewer, rechecked by 2 other reviewers, and combined with use of a random-effects model to determine the standardized mean difference (SMD).

Of 60 randomized controlled trials identified and included in the review, 49 were of sufficient methodologic quality to pool the data in meta-analyses and enrolled a total of 2333 participants given sublingual immunotherapy and 2256 given placebo. A total of 11 studies used sublingual tablets, 35 used sublingual drops, and 3 used both and were excluded from analysis.

Compared with participants receiving placebo, those receiving sublingual immunotherapy had significantly fewer symptoms (SMD, −0.49; 95% confidence interval [CI], −0.64 to −0.34; P < .00001) and lower medication requirements (SMD, −0.32; 95% CI, −0.43 to −0.21; P < .00001).

Within the subgroup of 15 trials looking exclusively at children, the treatment effect appeared to be similar to that seen in adults, especially when symptom scores were considered.

Severe systemic reactions or anaphylaxis were not reported in any of the 49 included trials. Although some systemic reactions were reported, adrenaline was not needed for treatment in any of these cases.

“This updated review reinforces the conclusion of the original 2003 Cochrane Review that sublingual immunotherapy is effective for allergic rhinitis and has been proven to be a safe route of administration,” the review authors write.

Limitations of this study include significant heterogeneity among the included studies and inability to differentiate the effects of various dosages.

“The optimum dose and duration of therapy remains an unanswered question and it is unlikely that meta-analysis will provide the answers,” the review authors conclude. “The mechanism of action of both injection and sublingual immunotherapy remain under investigation, and injection immunotherapy has been proven to lead to long-term changes in the immunological response to allergen that may persist for years following discontinuation.”

One of the study authors has disclosed a financial relationship with the Immune Tolerance Network. The Department of Upper Respiratory Medicine, National Heart & Lung Institute, London, United Kingdom, headed by Professor Durham, has received financial support from ALK Abello, Horsholm, Denmark (makers of allergen extracts).