Rhinitis, sinusitis, and upper airway disease
Safety and efficacy in children of an SQ-standardized grass allergen tablet for sublingual immunotherapy

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Background

Immunotherapy with the SQ-standardized grass tablet Grazax is efficacious and well-tolerated in adult patients with rhinoconjunctivitis. Allergic asthma and rhinoconjunctivitis are closely linked, and a strategy combining treatment of the upper and lower airways is recommended.

Objective

To investigate the efficacy of treatment with the grass tablet on grass pollen–induced rhinoconjunctivitis and asthma as well as the immunologic response and the safety profile in children.

Methods

A total of 253 children age 5 to 16 years, with grass pollen–induced rhinoconjunctivitis with/without asthma, were randomized 1:1 to active treatment or placebo. Treatment was initiated 8 to 23 weeks before the start of the grass pollen season 2007 and continued throughout the entire season. Symptomatic medication was provided as relief medication to both groups in a stepwise fashion. Primary endpoints were rhinoconjunctivitis symptom and medication scores.

Results

The rhinoconjunctivitis symptom and medication scores and the asthma symptom score were all statistically significantly different between the 2 treatment groups. The differences in medians relative to placebo were 24%, 34%, and 64% in favor of active treatment. The immunologic response was similar to that observed in adults. The most common adverse reaction was oral pruritus, reported by 40 subjects (32%) in the active and 3 (2%) in the placebo group. Six subjects withdrew because of adverse events. No serious adverse events were assessed as treatment-related.

Conclusion

Immunotherapy with the grass tablet reduced grass pollen–induced rhinoconjunctivitis and asthma symptoms in a pediatric population and introduced an immunomodulatory response, consistent with treatment of the underlying allergic disease. The treatment was well tolerated.

Section snippets

Trial population, design, and conduct

This was a multicenter, randomized, parallel-group, double-blind, placebo-controlled trial, initiated in autumn 2006. A total of 253 subjects age 5 to 16 from 26 centers in Germany were randomized 1:1 to once daily administration of either an orodispersible, fast-dissolving, SQ-standardized grass allergen tablet (Grazax; ALK, Hørsholm, Denmark; 75,000 SQ-T/2800 bioequivalent allergen units, approximately 15 μg Phl p 5, Phleum pratense major allergen 5) or a placebo tablet similar in taste,

Results

A total of 253 subjects were randomized, and 234 (92%) completed the trial. There were a total of 19 (8%) withdrawals from the trial. Of these withdrawals, 6 (2%) were due to adverse events (AEs), 4 (3%) in the active group and 2 (2%) in the placebo group. A diagram of the trial flow is presented in Fig 1.

The trial population comprised close to twice as many male as female subjects, and the majority (97%) were white. Generally, baseline parameters and vital signs were well balanced between the

Discussion

The efficacy of SCIT in treatment of IgE-mediated allergic disease is well established.1, 12 In recent years, SLIT has been intensively debated, with recent large phase III trials and meta-analyses supporting efficacy of this administration form as well, in adults.17, 19, 25 However, conflicting evidence has been presented regarding the efficacy of SLIT in children,26, 27 and 2 pediatric trials in Germany, where the current trial was conducted, failed to show reduction of rhinoconjunctivitis

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    Disclosure of potential conflict of interest: L. Kilmek has received research support from ALK Denmark, Stallergenes France, AllergoPharma Germany, HAL Netherlands, Artu Biologicals Netherlands, Bencord Great Britain, and Leti Spain and has served as an expert witness for Novartis Germany and GlaxoSmithKline Great Britain. B. Tholstrup is employed by ALK and holds ALK shares. J. Funck has received research support from ALK and MSD-Merck. The rest of the authors have declared that they have no conflict of interest.

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