Immunotherapy
Sublingual grass allergen tablet immunotherapy provides sustained clinical benefit with progressive immunologic changes over 2 years

https://doi.org/10.1016/j.jaci.2007.10.039Get rights and content

Background

This is an interim analysis of a randomized, double-blind, placebo-controlled phase III trial with 3 years of daily treatment with grass tablet immunotherapy (GRAZAX; ALK-Abelló A/S, Hørsholm, Denmark) or placebo, followed by 2 years of follow-up to assess the persistent efficacy.

Objective

We sought to evaluate the efficacy and safety of specific immunotherapy with grass allergen tablets compared with placebo after treatment covering 2 consecutive grass pollen seasons.

Methods

The interim analyses included 351 adult participants with moderate-to-severe allergic rhinoconjunctivitis caused by grass pollen. Participants were treated with active (n = 189) or placebo (n = 162) tablets for an average of 22 months. All participants were allowed to use symptomatic rescue medication.

Results

The primary efficacy analysis showed highly significant mean reductions of 36% in rhinoconjunctivitis symptom score (P < .0001; median reduction, 44%) and 46% in rhinoconjunctivitis medication score (P < .0001; median reduction, 73%) in the active group relative to the placebo group. Mean rhinoconjunctivitis quality of life was 33% better (P < .0001; median, 40%). Clinical improvements were paralleled by significant changes in allergen-specific immunoglobulins. The treatment was well tolerated, and adverse events led to withdrawal in less than 1% of participants. There were no serious adverse events related to treatment.

Conclusion

Grass allergen tablet immunotherapy showed progressive immunologic changes and highly significant efficacy over 2 years of continued treatment.

Section snippets

Clinical trial design

A randomized, parallel-group, double-blind, placebo-controlled, multicenter trial was performed. The trial is an extension of a previously published trial in which participants received double-blind treatment from the autumn of 2004 until the end of the grass pollen season of 2005.14 Three hundred fifty-one participants from 43 sites in 7 countries continued treatment with grass allergen tablets or placebo and will continue treatment until the end of the grass pollen season of 2007. The

Results

Five hundred forty-six participants completed the first year of the trial. Because of closure of a few trial centers, only 472 could be offered to continue in the extension. Three hundred fifty-one accepted participation in the extension period of the trial and continued doubled-blind treatment after the grass pollen season of 2005. A diagram of the trial flow is presented in Fig 1. Three hundred nineteen participants were in the trial when the grass pollen season of 2006 started, and 306 were

Discussion

The present data are from an extension of a trial in which approximately 65% of completers from the original trial chose to continue double-blinded treatment during the extension. Different analyses were performed to investigate whether the population that continued in the extension of the trial was representative for the entire population during the first year of the trial. The analyses demonstrated that both demographics and symptom and medication scores for the first year of treatment were

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    Sponsored by ALK-Abelló A/S, Hørsholm, Denmark.

    Disclosure of potential conflict of interest: A. Kapp is on the speakers' bureau for ALK-Abelló, UCB, Novartis, and Astella. B. Riis is employed by ALK-Abelló. S. R. Durham has consulting arrangements and has received grant support from ALK-Abelló and GlaxoSmithKline and is on the speakers' bureau for ALK-Abelló, GlaxoSmithKline, and Allergy Therapeutics. The rest of the authors have declared that they have no conflict of interest.

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