Level 1: Likely reliable evidence

Immunotherapy may be effective in patients with persistent allergic rhinitis symptoms who have failed other treatments. Therapy is generally provided in the form of “allergy shots” given subcutaneously according to a schedule (often weekly) of carefully titrated antigen doses. The injections may be discontinued after four to five years because immunoglobulin (Ig) E levels remain low and patients show continued improvement in signs and symptoms.

The use of sublingual or oral immunotherapy avoids the risk of anaphylaxis, but the necessarily large doses cause GI distress. Sublingual or oral immunotherapy is also 10 times more costly than subcutaneous immunotherapy.


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Sublingual immunotherapy is safe and reduces symptoms in allergic rhinitis, based on a systematic review of 22 randomized placebo-controlled trials with 979 patients (Cochrane Database Syst Rev. 2003[2]:CD002893). A subsequent trial evaluated sublingual immunotherapy with grass-allergen (Phleum pratense) tablets in 855 participants 18-55 years old who had timothy grass pollen-induced allergic rhinoconjunctivitis, positive skin prick test, and elevated IgE (J Allergy Clin Immunol. 2006;117:802-809).

Participants were randomized to receive double-blind grass-allergen tablets (2,500, 25,000, or 75,000 units; equivalent to 0.5, 5, or 15 µg) or placebo sublingually once daily for mean 18 weeks (starting eight weeks before grass-pollen season). They were also assigned to single-blind loratadine or placebo rescue therapy, followed by open-label budesonide nasal spray and oral prednisone if needed. All patients were included in the intention-to-treat analysis; 790 (92%) completed the trial.

Comparing the 75,000-unit grass-allergen tablets with placebo, the mean symptom score during the entire grass-pollen season was 2.6 vs. 3.1 (P =.014). The mean symptom score during the entire grass-pollen season within a subgroup that received at least eight weeks of preseasonal treatment was 2.5 vs. 3.2 (P =.002). Most patients had mild adverse events.