High-Dose Liquid Birch Pollen Extract Safely Reduced Symptoms in Adults With Pollen Allergies, Trial Results Show

Adults with birch pollen allergies who took high-dose liquid birch pollen extract under the tongue experienced significant reductions in their symptoms after 3 to 6 months, compared with adults taking placebo, according to results of a pivotal phase III trial.¹

The study involved adults with moderate to severe allergic rhinoconjunctivitis, with or without mild to moderate controlled asthma, according to results to be published in the Journal of Allergy and Clinical Immunology.²

The study also showed that patients treated with the birch pollen extract reported improved quality-of-life (QOL) scores and overall self-assessment of their health status, as well as a good safety profile.

Allergic rhinoconjunctivitis (ARC) is a symptomatic disorder of the upper airways caused by an immunoglobulin E (IgE)-mediated inflammatory response in sensitized subjects following allergen exposure. It is considered a major risk factor for developing asthma if left untreated. Allergen immunotherapy is the only disease-modifying treatment option available for patients with IgE-mediated allergic diseases, and it can be administered sublingually.

Oliver Pfaar, MD, and European colleagues conducted a randomized, double-blind, placebo-controlled, parallel group multicenter trial in 406 adult patients who had lived with confirmed moderate-to-severe birch pollen-induced allergic rhinoconjunctivitis for at least 2 consecutive years. Some patients also had mild to moderate controlled asthma due to sensitization to birch pollen. All patients had to be willing and able to complete an e-diary during birch pollen season. Of the study group, 208 were on the study therapy; 198, placebo.

Study medications were taken sublingually once daily. After daily increase by 1 drop, the maintenance dose was reached at 5 drops/day (40,000 AUN/mL). Drops were held 2.3 minutes beneath the tongue and then swallowed. Treatment compliance was checked based on the daily study medication use entered into the e-diary and on returned used/unused bottles at the end of study site visits.

Treatment was started 3 to 6 months prior to the September 2014-May 2015 birch pollen season and continued during the season in 40 clinical study centers in 5 European countries (Germany, Belgium, Poland, Czech Republic, and Slovakia). The primary end point was the combined symptom and medication score (CSMS; European Academy of Allergy and Clinical Immunology [EAACI]). CSMS is the sum of daily symptom score (comprising 6 individual symptom scores: 4 nasal symptoms and 2 ocular symptoms rated on a scale of 0 to 3) plus daily medication score (0, no rescue medication; 1, antihistamines; 2, nasal corticosteroids, 3, oral corticosteroids). Secondary end points included QOL assessments, immunological parameters, and safety. A 6-month open-label extension study (June 2015 to February 2016) included 343 patients who completed the double-blind phase of the study; they were treated exclusively with active product.

Safety and tolerability of active versus placebo treatment was assessed by number and severity of local and systemic reactions, adverse events, laboratory parameters such as hematology and blood chemistry, urinalysis, vital signs, ECG, physical examination, lung function test, and use of concomitant medications.

Researchers demonstrated a significant (P<0.0001) and clinically relevant (32%) reduction in the CSMS during the pollen season in the active compared with placebo group after 3 to 6 months of sublingual allergen immunotherapy (SLIT). A treatment effect on general health-related QOL could also be shown, researchers said. During the pollen season, there was a statistically significant improvement in change from baseline EQ-VAS scores between active and placebo patients (active: mean EQ-VAS, -3.95 [SE, 1.27]; placebo: EQ-VAS, -8.72 [SE, 1.27]; difference [95% Confidence Interval]: 4.77 [1.68, 7.86]; P = 0.0025).

Significantly better rhinoconjunctivitis QOL scores (P<0.0001) and patients’ own overall assessment of their health status (visual analogue scale (EQ-VAS], P = 0.0025) were also shown. Researchers reported a good safety profile, with local and systemic adverse reactions that were mostly of mild intensity and well controlled. The researchers said that like other recent reviews of high-dosage SLIT, local reactions are common and much more frequent in the active as compared with the placebo group, and that frequency and severity of adverse events decrease over time with treatment.

“Unequivocal evidence for significant and clinically relevant efficacy for this birch SLIT product was shown,” the researchers conclude. The observed treatment effect size of 32% exceeds the recommendations of the World Allergy Organization regarding minimal clinically relevant efficacy of 20%, they said.

HAL Allergy B.V., Leiden, The Netherlands, the manufacturer of the SLIT used, funded the study.

References

1. SUBLIVAC FIX Birch Phase III Short-term Efficacy. clinicaltrials.gov/ct2/show/NCT02231307. Updated September 23, 2016. Accessed December 26, 2018.
2. Pfarr O, Bachert C, Kuna P, et al. Sublingual allergen immunotherapy with a liquid birch pollen product in seasonal allergic rhinoconjunctivitis with/without asthma. J Allergy Clin Immunol. 2018; Accepted manuscript. https://doi.org/10.1016/j.jaci.2018.11.018?rel=0" ?rel=0" .