Rhinitis, sinusitis, and upper airway disease
Long-term clinical efficacy in grass pollen–induced rhinoconjunctivitis after treatment with SQ-standardized grass allergy immunotherapy tablet

https://doi.org/10.1016/j.jaci.2009.10.035Get rights and content

Background

Sustained and disease-modifying effects of sublingual immunotherapy have never before been confirmed in a large-scale randomized, double-blind, placebo-controlled trial.

Objective

We sought to investigate sustained efficacy 1 year after a 3-year period of daily treatment with the SQ-standardized grass allergy immunotherapy tablet Grazax (Phleum pratense 75,000 SQ-T/2,800 BAU; ALK-Abelló, Hørsholm, Denmark).

Methods

A randomized, double-blind, placebo-controlled, phase III trial including adults with a history of moderate-to-severe grass pollen induced rhinoconjunctivitis inadequately controlled by symptomatic medications. The analysis set comprised 257 subjects at the follow-up. Efficacy end points were rhinoconjunctivitis symptom and medication scores, quality of life, and percentages of symptom and medication free days. Immunologic end points included grass pollen–specific serum IgG4 and IgE-blocking factor. Safety was assessed based on adverse events.

Results

Significant improvements in efficacy were consistently shown during 3 years' treatment. One year after treatment, the active group showed sustained reductions in mean rhinoconjunctivitis symptom scores (26%, P < .001) and medication scores (29%, P = .022) when compared with placebo. This level was similar to the efficacy observed during the 3-year treatment period. The differences in percentages of symptom- and medication-free days were significant during and 1 year after treatment. The active group also reported sustained and significant improvements in quality of life. Sustained clinical benefit was accompanied by immunologic changes. No safety issues were identified.

Conclusion

Three years of treatment with the SQ-standardized grass allergy immunotherapy tablet resulted in consistent clinical improvement and accompanying immunologic changes that were sustained 1 year after treatment, which is indicative of disease modification and associated long-term benefits.

Section snippets

Clinical trial design

Details of the randomized, double-blind, placebo-controlled trial conducted according to the Declaration of Helsinki20 at 43 centers in 7 countries have been published previously (see also ClinicalTrials.gov no. NCT00227279).18, 19 From originally 1 year of treatment, the trial was extended to cover 3 years of treatment and 2 years of follow-up to investigate long-term and sustained efficacy (extension implemented April 20, 2005). The ethics committees in each country approved the trial, as

Results

An overview of the subjects during the third year of treatment (2007) and during the follow-up year (2008) is provided in Fig 1. Diary data during the 2007 grass pollen season were obtained from 287 subjects (160 in the active group and 127 in the placebo group) and during 2008 from 257 subjects (142 in the active group and 115 in the placebo group). A complete overview of the trial is available in Fig E1 in this article's Online Repository at www.jacionline.org.

At inclusion, all subjects had a

Discussion

This study has, for the first time in a large-scale, placebo-controlled trial, demonstrated that sublingual tablet immunotherapy has the ability to provide a statistically significant and clinically relevant, sustained disease-modifying effect 1 year after the completion of a 3-year treatment period. This effect was clearly demonstrated by the consistent improvements in nasal and ocular symptoms, use of symptomatic medications, and rhinoconjunctivitis quality of life in the active group. The

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  • Cited by (0)

    The trial is sponsored by ALK-Abelló, Hørsholm, Denmark. S.R.D. has consultant arrangements with, has received grant support from, and is on the speakers' bureau for ALK-Abelló. A.K. has consultant arrangements with DPC; has received grant support from Novartis, Astellas, UCB, ALK-Abelló, and DPC; and is on the speakers' bureau for Novartis, Astellas, UCB, and ALK. J.G.R.d.M. has received a grant from ALK-Abelló. S.R. has received grant support from the Swedish Asthma and Allergy Association. R.D. has consultant arrangements with Altana, GlaxoSmithKline, Boehringer Ingelheim, Novartis, and Fertin and has received grant support from Altana, GlaxoSmithKline, Boehringer Ingelheim, Novartis, AstraZeneca, ALK-Abelló, Roche, and Pfizer. G.K.S. has been on advisory boards and is on the speakers' bureau for ALK-Abelló and is advisor and speaker for Schering-Plough. J.S.A. and B.R. are employed by ALK-Abelló.

    Disclosure of potential conflict of interest: S. R. Durham has received research support from ALK-Abelló and GlaxoSmithKline. W. Emminger and A. Kapp have received research support from ALK-Abelló. J. G. R. de Monchy has received research support from Novartis, Organon (Schering-Plough), and ALK-Abelló. S. Rak has received honoraria from Stallergenes, ALK-Abelló, and Allergopharma and has received research support from ALK-Abelló and Allergopharma. G. K. Scadding is on an advisory board for and has given lectures sponsored by ALK-Abelló and has received research support from ALK-Abelló and GlaxoSmithKline. J. S. Andersen and B. Riis are employees of ALK-Abelló. G. Colombo has declared that she has no conflict of interest.

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