Long-Term Effects of Sublingual Grass Therapy (GRASS)

Subcutaneous immunotherapy (SCIT) to treat allergic rhinitis due to grass pollen is known to be effective and induce prolonged remission for several years after its discontinuation. However subcutaneous immunotherapy may occasionally be associated with allergic side effects and therefore requires administration in a specialist clinic.

An alternative strategy using sublingual immunotherapy (with Grazax®, a once daily grass immunotherapy sublingual tablet) has been previously shown to be clinically effective with an approximate 30% reduction in symptom scores and a 40% reduction in medication use during the summer months. One study showed that three years treatment with Grazax resulted in clinical benefit that persisted for at least one year following its discontinuation. Further studies are needed to confirm or refute this possibility.

The present study proposes to investigate the long-term effects of sublingual immunotherapy (SLIT) in severe hay fever using subcutaneous immunotherapy as a positive control. The primary goal is to determine whether SLIT induces tolerance and if so, by what mechanism. In this study, we hypothesize that sublingual immunotherapy induces suppression of allergen-induced early and late-phase nasal responses that persist for at least 1 year after discontinuation of treatment. We further hypothesize that sublingual immunotherapy results in long-lived “protective” inhibitory antibody responses. Although not powered for a head-to-head comparison with SCIT, it is hoped that this trial may provide data to support a definitive head-to-head efficacy trial in the future.

This is a randomized, double-blind, single-center, placebo-controlled, three-arm study comparing SLIT with placebo and SCIT with placebo. The main comparison will be between SLIT and placebo.
Individuals with severe grass pollen hay fever, with or without associated seasonal asthma, will be recruited during the pollen season of March through September 2011. Participants will receive treatment over a 2-year period followed by a 1-year blinded withdrawal phase. They will be provided with antiallergic rescue medications (antihistamine, topical intranasal corticosteroids, and short-acting beta agonists) throughout the study. Clinical endpoint assessments will be performed at baseline, after 1 and 2 years of treatment, and after the 1-year withdrawal period at 3 years.

Measurement of early (0–60 min) and late (1–10 hours) responses will be performed before and at intervals after immunotherapy. Nasal fluid and samples of peripheral blood for T cell and B cell assays will be performed at corresponding time points, and nasal biopsies will be collected at the end of the withdrawal phase. Exploratory analyses will relate changes in the target organ after challenge to nasal symptoms, medication use, and the quality of life of participants during natural allergen exposure during the pollen season.