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Randomized Controlled Trial
. 2018 May;141(5):1744-1749.
doi: 10.1016/j.jaci.2017.09.051. Epub 2017 Dec 5.

Effect of grass sublingual tablet immunotherapy is similar in children and adults: A Bayesian approach to design pediatric sublingual immunotherapy trials

Amarjot Kaur  1 , David Skoner  2 , Joseph Ibrahim  3 , Qing Li  1 , Richard F Lockey  4 , Michael Blaiss  5 , Albrecht Bufe  6 , Jens Strodl Andersen  7 , Giorgio Walter Canonica  8 , Hendrik Nolte  9
Affiliations
Randomized Controlled Trial

Effect of grass sublingual tablet immunotherapy is similar in children and adults: A Bayesian approach to design pediatric sublingual immunotherapy trials

Amarjot Kaur et al. J Allergy Clin Immunol. 2018 May.

Abstract

Background: Large sample sizes are needed for sublingual immunotherapy (SLIT) trials because of inherent data variability secondary to inconsistent allergen exposure. Obtaining large sample sizes for pediatric SLIT trials is challenging, but a Bayesian approach using prior adult data can reduce the necessary sample size.

Objective: We sought to describe how a Bayesian framework using prior information from adult trials can be used to improve pediatric SLIT clinical development.

Methods: Data were compiled by using a frequentist approach (conventional clinical trial approach independent of prior data) from trials conducted during the clinical development of timothy grass SLIT-tablets.

Results: The treatment effect of timothy grass SLIT-tablets was considered similar between pediatric (n = 795) and adult (n = 2299) data pools, with relative total combined symptom plus medication score improvement versus placebo of 21% (95% CI, 11.0% to 30.4%) and 20% (95% CI, 14.6% to 24.4%), respectively. Phleum pratense-specific IgG4 and IgE-blocking factor increased from baseline in both children and adults treated with timothy grass SLIT-tablets. Given the reasonable assumption in similarity of treatment response between adults and children, a Bayesian approach is described to demonstrate rigorous efficacy criteria for pediatric trials incorporating information from prior adult trials and thereby reduce the sample size.

Conclusions: Data support the similarity of efficacy and immunologic changes between children and adults treated with SLIT for allergic rhinoconjunctivitis. Therefore it is appropriate to use data from adult trials to design feasible trials in children, which might reduce unsafe off-label use by promoting more quickly proper labeling of approved products.

Keywords: Bayesian framework; IgG(4); Sublingual immunotherapy; adults; children; efficacy; frequentist; trial design.

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Conflict of interest statement

Disclosure of potential conflict of interest: A. Kaur is employed by and holds stock/stock options in Merck. D. Skoner receives consulting fees or honoraria from Mylan, Genentech, and ALK-Abelló and payment for lectures, including service on speakers’ bureaus, from Mylan and Greer. Q. Li is employed by Merck. R. F. Lockey holds board membership with the Journal of Allergy and Clinical Immunology: In Practice; receives consultancy fees from Merck and AstraZeneca; is employed by the University of South Florida College of Medicine; receives payment for lectures, including service

on speakers’ bureaus, for Merck and AstraZeneca; receives royalties from Informa Publishing; receives payment for development of educational presentations from Merck and AstraZeneca; and has received travel/accommodations/meeting expenses unrelated to activities listed for national and international congresses for presentations. M. Blaiss reports personal and other fees from Merck, personal fees from ALK-Abelló, and personal fees from Stallergenes/Greer outside the submitted work. J. S. Andersen is an employee of ALK-Abelló. H. Nolte is employed by ALK-Abelló. The rest of the authors declare that they have no relevant conflicts of interest.

Figures

FIG 1.
FIG 1.
Summary by age of mean change from baseline in log10 IgG4 levels at the end of the season in pooled timothy grass SLIT-tablet trials. n, Number of subjects with IgG4 at the end of the season.
FIG 2.
FIG 2.
Summary by age of mean change from baseline in IgE-blocking factor at the end of the season in pooled timothy grass SLIT-tablet trials. n, Number of subjects with IgE-blocking factor at the end of the season.
See this image and copyright information in PMC

References

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