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

Abstract

Background: Allergic 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.

Methods: Birch 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.

Results: 574 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.

Conclusions: Pre- 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 registration: ClinicalTrials.gov: NCT01731249.

Figures

Figure 1

Study design. The no-treatment period was about 7 months.

Figure 2

Patient disposition. Patients were randomized to receive either placebo or 300IR sublingual solution of birch allergen extract initiated approximately 4 months before the birch pollen season and continued through it. Patients were treated discontinuously for two consecutive years.

Figure 3

Average Adjusted Symptom Score. Data are presented for the overall population and by baseline OAS status during Periods 1 (A) and 2 (B, Primary Endpoint) in the FASP1 and FASP2. ANCOVA *p < 0.05; **p < 0.001; ***p < 0.0001.

Figure 4

Daily mean Adjusted Symptom Score and birch pollen season. Data are presented for Periods 1 (A) and 2 (B) in the FASP1 and FASP2. The daily mean birch pollen count (grains/m3) was the average of pollen count weighted by the number of patients within the catchment area of each pollen trap.

Figure 5

Symptoms and medication scores. Average Rescue Medication Score (A), Average Rhinoconjunctivitis Total Symptom Score (B) and Average Rhinoconjunctivitis Symptom Scores (C) for Periods 1 and 2 in the FASP1 and FASP2. ANCOVA *p < 0.05; **p < 0.001; ***p < 0.0001.

Figure 6

Standardized Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ[S]) overall scores. Data are presented for birch pollen Periods 1 and 2 in the FASP1 and FASP2. Linear mixed effects model with repeated measures *p < 0.05; **p < 0.001.

Figure 7

Immunological markers (FASP1, FASP2). Serum specific-IgG4 levels (A) and serum specific-IgE levels (B) at baseline, at the end of pollen period (Period 1), 4 months before the pollen period (Period 2) and at the end of the pollen period (Period 2).