Sustained efficacy and safety of a 300IR daily dose of a sublingual solution of birch pollen allergen extract in adults with allergic rhinoconjunctivitis: results of a double‐blind, placebo‐controlled study

Margitta Worm,Michel Melac,Robert K Zeldin,Véronique Cadic,Frédéric De Blay,Sabina Rak,Hans‐Jorgen Malling

doi:10.1186/2045-7022-4-7

Abstract

BackgroundAllergic rhinoconjunctivitis (ARC) due to birch pollen is a growing health concern in Europe. Here, we report the efficacy and safety of 300IR birch pollen sublingual solution administered discontinuously for 2 consecutive years to patients with birch-associated allergic rhinoconjunctivitis.MethodsBirch pollen-allergic adults were randomized in this double blind study to 300IR birch pollen sublingual solution or placebo, daily, starting 4 months before and continuing through the pollen season for two pollen seasons. Randomization was stratified according to the presence or absence of oral allergy syndrome (OAS). The primary efficacy endpoint was the Average Adjusted Symptom Score (AAdSS) over the second pollen season and was analyzed by ANCOVA. Secondary efficacy endpoints included the AAdSS over the first pollen period. Safety was evaluated by means of adverse event monitoring.Results574 patients (284 in the active group and 290 in the placebo group) were randomized and 496 completed the study. Over the second pollen period, the least square (LS) mean AAdSS was significantly lower in the 300IR group than in the placebo group (LS mean difference −2.04, 95% CI [−2.69, −1.40], (p <0.0001) with a relative reduction of 30.6%. Results were consistent in patients with and without OAS (−33.6% and −28.4%, respectively). A significant reduction in LS mean AAdSS was also observed over the first pollen season. The most frequently reported adverse events were application site reactions: oral pruritus, throat irritation, and mouth edema. There were no reports of anaphylaxis.ConclusionsPre- and co-seasonal treatment with 300IR birch pollen sublingual solution demonstrated sustained clinical efficacy over 2 pollen seasons and was well tolerated in adults with birch pollen-associated allergic rhinoconjunctivitis. Efficacy results were consistent in patients with and without oral allergy syndrome.Trial registrationClinicalTrials.gov: NCT01731249.

Highlights

Allergic rhinoconjunctivitis (ARC) due to birch pollen is a growing health concern in Europe
Demographics and baseline characteristics were similar in the two groups at study entry and remained so at the start of the second study year (Table 1)
The average patient had a history of birchassociated allergic rhinitis for about 14 years, more than 68% were polysensitized, 20% had asthma, and about 54% had oral allergy syndrome (OAS)

Summary

Introduction

Allergic rhinoconjunctivitis (ARC) due to birch pollen is a growing health concern in Europe. Cross-reactivity to alder and hazel contributes to a prolonged tree pollen season in patients with birch pollen allergy [3]. In addition to allergic rhinoconjunctivitis (ARC) symptoms, 50% to 93% of birch pollen allergic patients develop an oral allergy syndrome (OAS), with oropharyngeal symptoms after eating certain foods, because of the cross-reactivity between the major birch pollen allergen, Bet v 1, and the food proteins [4,5,6]. Symptomatic treatment options include antihistamines, intranasal corticosteroids, and leukotriene modifiers. These provide temporary relief from allergy symptoms but are not effective in all patients and are not disease-modifying [7]. WAO Guidelines recommend AIT by subcutaneous (SCIT) or sublingual (SLIT) route as therapeutic options for patients whose symptoms are not adequately controlled by avoidance measures or medications, those experiencing unacceptable adverse effects of medications, or those who wish to reduce the long-term use of medications [10,11]

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