December 13, 2010 — Sublingual immunotherapy may be safe and effective for allergic rhinitis, according to an updated review reported online December

Allergic rhinitis has been reported in up to 40% of people worldwide. According to the 2008 guidelines on Allergic Rhinitis and its Impact on Asthma (ARIA), published in the April 2008 supplemental issue of Allergy, specific immunotherapy is recommended for patients with severe allergic rhinitis who do not respond to allergen avoidance and pharmacotherapy.

The 2003 Cochrane Review of sublingual immunotherapy for allergic rhinitis by Wilson and colleagues, published in the 2003 issue of the Cochrane Database of Systematic Reviews, included 22 randomized, placebo-controlled trials. Sublingual immunotherapy was noted to be effective and was not associated with systemic reactions.

This update of the 2003 Cochrane Review evaluates the efficacy and safety of sublingual immunotherapy for allergic rhinitis in adults and children.

Study Highlights
•A search of the literature included the Cochrane ENT Disorders Group Trials Register, the Cochrane Central Register of Controlled Trials, PubMed, EMBASE, CINAHL, LILACS, KoreaMed, IndMed, PakMediNet, CAB Abstracts, Web of Science, BIOSIS Previews, China National Knowledge Infrastructure, Current Controlled Trials, International Clinical Trials Registry Platform, Google, reference lists, and other sources for published and unpublished data through August 14, 2009.
•Inclusion criteria were randomized, double-blind, placebo-controlled clinical trials that assessed the efficacy and safety of sublingual immunotherapy in adults and children with allergic rhinitis and a Jadad score greater than 3 of 5.
•60 studies were identified.
•49 studies were included in the efficacy meta-analysis.
•11 studies lacked efficacy data but had adverse event data.
•Subjects had allergic rhinitis with or without allergic conjunctivitis or allergic asthma.
•Allergens were identified by skin prick tests or high specific immunoglobulin E results.
•34 studies had adult participants, and 15 studies had children as participants.
•The primary outcome measures were symptom scores and medication scores.
•Symptom scores were assessed by diaries, visual analog scales, number of well days, or overall assessment.
•Medication scores assessed the use of antihistamine tablets, nasal sprays, and eye drops.
•Secondary outcome measures were serum immunoglobulin E and immunoglobulin G levels; allergen sensitivity of the eye, nose, or skin; and reports of adverse events.
•Subgroup analysis was conducted for seasonal vs perennial allergens, children vs adults, major allergen dose (< 5 μg vs 5 to 20 μg vs > 20 μg), duration of immunotherapy (< 6 months vs 6 - 12 months vs 12 months), individual allergens (house dust mite, grass pollen, Parietaria, ragweed, tree), sublingual spit vs swallow, and sublingual drops vs tablets.
•Symptom scores improved more in 2333 patients receiving sublingual immunotherapy vs 2256 patients receiving placebo. The SMD was −0.49 (P < .00001), based on 49 studies.
•Medication scores improved more in 1737 patients receiving sublingual immunotherapy vs 1642 patients receiving placebo (SMD, −0.32; P < .00001), based on 38 studies.
•Serum-specific immunoglobulin E levels increased in 675 patients receiving sublingual immunotherapy vs 659 patients receiving placebo (SMD, 0.27; P = .05), based on 14 studies.
•Total serum-specific immunoglobulin G levels increased in 286 patients receiving sublingual immunotherapy vs 304 patients receiving placebo (SMD, 0.95; P < .00001), based on 3 studies.
•Serum-specific immunoglobulin G4 levels increased in 588 patients receiving sublingual immunotherapy vs 599 patients receiving placebo (SMD, 0.46; P < .00001).
•Allergen sensitivity, measured by skin prick test results and nasal reactivity, did not significantly differ between the sublingual immunotherapy group and the placebo group.
•25 studies could not be included in adverse event analysis.
•Local adverse events, including labial edema, buccal pruritus, buccal or lingual edema, and throat irritation, were more common in the sublingual immunotherapy group vs the placebo group.
•Adverse events leading to treatment discontinuation occurred in 41 of 824 patients in the sublingual immunotherapy group and 12 of 861 patients in the placebo group, with local reactions occurring more than systemic reactions.
•No adverse events required adrenaline use.
•No fatalities occurred.
•Systemic adverse events were mild or moderate.
•No severe systemic adverse events or anaphylaxis events occurred.
•Subgroup analysis of symptom scores showed more improvement in the sublingual immunotherapy group vs the placebo group for all subgroups except for a major allergen content of less than 5 μg.
•Subgroup analysis of medication scores showed more improvement in the sublingual immunotherapy group vs the placebo group for all subgroups except for perennial allergens, children, house dust mite allergen, and sublingual drops.

Clinical Implications
•In adults and children with allergic rhinitis, sublingual immunotherapy is effective in reducing symptoms and the need for medication.
•In adults and children who receive sublingual immunotherapy for allergic rhinitis, reported adverse events include local and systemic mild and moderate events, but no severe systemic reactions, anaphylaxis, or the need for adrenaline.