Rhinitis, sinusitis, and upper airway disease
Clinical efficacy of 300IR 5-grass pollen sublingual tablet in a US study: The importance of allergen-specific serum IgE

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Background

Previous trials have demonstrated the efficacy, safety, and optimal dosage of the 5-grass pollen sublingual tablet for adults and children with grass pollen–induced allergic rhinoconjunctivitis.

Objectives

We sought to evaluate the efficacy and safety of 300 index of reactivity (IR) 5-grass pollen sublingual tablet in US adults.

Methods

Adults with grass pollen allergy and Rhinoconjunctivitis Total Symptom Scores of 12 or greater (scale, 0-18) during the previous grass pollen season were randomized in a double-blind, placebo-controlled study to receive 300IR 5-grass pollen sublingual tablet or placebo starting 4 months before and continuing through the pollen season. The primary efficacy end point was the daily Combined Score (CS; scale, 0-3), which integrates symptoms and rescue medication use.

Results

Four hundred seventy-three participants were randomized. The mean daily CS over the pollen period was significantly lower in the active treatment group versus the placebo group (least-squares mean difference: −0.13; 95% CI, −0.19 to −0.06; P = .0003; relative reduction: 28.2%; 95% CI, 13.0% to 43.4%). In placebo-treated participants, the daily CS least-squares mean was 0.32 in the subgroup with baseline timothy grass–specific serum IgE of less than 0.1 kU/L (n = 23) and 0.46 in those with baseline timothy grass–specific serum IgE of 0.1 kU/L or greater (n = 204). The most frequent reported adverse events were oral pruritus, throat irritation, and nasopharyngitis. There were no reports of anaphylaxis, and no actively treated participant received epinephrine.

Conclusion

In US adults with grass pollen–induced allergic rhinoconjunctivitis, preseasonal and coseasonal treatment with 300IR 5-grass pollen sublingual tablet demonstrated clinically meaningful efficacy, especially in study subjects with measurable timothy grass–specific serum IgE. Use of 300IR 5-grass pollen sublingual tablet was safe and well tolerated. A requirement for a measurable level of allergen-specific serum IgE should be considered in future studies in this field.

Section snippets

Study design

This was a double-blind, placebo-controlled, parallel-group, randomized, multicenter study conducted at 51 sites in the United States (ClinicalTrials.gov no. NCT00955825). Written informed consent was obtained from all participants before study entry. The study was conducted in accordance with International Conference on Harmonisation good clinical practice and approved by the appropriate institutional review boards and the US Food and Drug Administration.

Study subjects were enrolled between

Results

Four hundred seventy-three participants were randomized to active treatment (n = 233) or placebo (n = 240, Fig 2). Because 35 study subjects did not have at least 1 CS during the pollen period while receiving treatment, the FAS consisted of 438 participants: 210 in the 300IR group and 228 in the placebo group.

The FAS included 53% women. The mean age was 37.2 years (SD, 11.46 years). Most participants (78%) were polysensitized (in decreasing order of frequency) to ragweed, trees (oak, ash,

Discussion

This US study was conducted in adults with grass pollen–induced ARC. The primary efficacy end point was the daily CS, which takes into account symptoms and rescue medication use consistent with WAO recommendations.20 The 28.2% relative LS mean difference versus placebo in daily CS during the pollen period exceeded the 20% value recommended by the WAO taskforce for standardization of clinical trials with allergen-specific immunotherapy for respiratory allergy as clinically relevant for efficacy.

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    Supported by Stallergenes SA, Antony, France.

    Disclosure of potential conflict of interest: L. S. Cox has received consulting fees, honoraria for lectures, and/or research funding from Genentech/Novartis, Teva, Baxter, Thermo Fisher and Stallergenes. T. B. Casale has received consultancy fees from Stallergenes; has received research support from Stallergenes and Merck/Schering-Plough; is on the World Allergy Organization Board of Directors; and is the American Academy of Allergy, Asthma & Immunology (AAAAI) Executive VP. A. S. Nayak is an employee of Sneeze, Wheeze, and Itch Associates LLC and has received research grants, educational support, honoraria, and/or consultancy fees from Stallergenes. D. I. Bernstein has received research support from Stallergenes, Merck, and Greer; is a member of the AAAAI Immunotherapy Committee; and has received consultancy and advisory fees from Merck and ALK-Abelló. P. S. Creticos is a consultant to Circassia, Greer Laboratories Merck/Schering-Plough, Stallergenes, and UpToDate; has received grant support from AHRQ, Greer Laboratories, Merck/Schering-Plough, and Stallergenes; and has committee assignments for the AAAAI and American College of Allergy, Asthma & Immunology. The rest of the authors declare that they have no relevant conflicts of interest.

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