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. 2014 Jul 23:4:23.
doi: 10.1186/2045-7022-4-23. eCollection 2014.

A prospective study comparing the efficacy and safety of two sublingual birch allergen preparations

Ludger Klimek  1 , Annette Sperl  1 , Esther van Twuijver  2 , Ronald van Ree  3 , Huub Kleinjans  2 , Johan Diderik Boot  2 , Oliver Pfaar  1
Affiliations

A prospective study comparing the efficacy and safety of two sublingual birch allergen preparations

Ludger Klimek et al. Clin Transl Allergy. .

Abstract

Background: SUBLIVAC FIX Birch (SUB-B) is a liquid oral preparation of Betula verrucosa pollen extract for the treatment of allergic rhinitis/rhinoconjuctivitis induced by birch pollen. The major allergen content of SUB-B and Staloral Birch (Stal-B) have been shown to be comparable. In order to compare the clinical efficacy and safety of both products, the present study was designed to investigate efficacy of treatment with SUB-B compared to Stal-B by means of reduction in allergy symptoms assessed by a titrated nasal provocation test (TNPT) in subjects suffering from IgE mediated allergy complaints triggered by birch pollen.

Methods: A prospective, randomized, open, blinded endpoint (PROBE), controlled, single-centre study in 74 birch allergic adults was performed. Treatment consisted of either SUB-B (10,000 AUN/ml) or Stal-B (initial phase 10 I.R./ml and maintenance phase 300 I.R./ml) for 16-20 weeks at maintenance dose. The primary efficacy outcome was defined by the difference in change of the TNPT-threshold dose between the two treatment groups at baseline and after completion of treatment. Secondary outcomes included determination of birch pollen specific IgE and IgG levels, safety lab and ECG. During the first 30 days of treatment, subjects were requested to fill out a diary concerning compliance with study medication, occurrence of AEs and the use of concomitant medication.

Results: Analysis of the primary efficacy parameter showed that the percentage of subjects showing a beneficial treatment effect was similar in both treatment groups, 33.3% for SUB-B vs. 31.4% for Stal-B in the intention to treat population. Evaluation of the immunologic response, showed that treatment with SUB-B and Stal-B induced similar increases (approximately 2 times) in IgE, IgG and IgG4 specific for Bet v 1. In total, 143 related adverse events (AEs) were reported. The majority of the AEs was of mild intensity. The same pattern of AEs was observed for both products. No clinically relevant changes in other safety parameters, such as safety laboratory parameters, vital signs, physical examination and ECGs were observed.

Conclusion: Taken together, treatment with both products was effective by means of reduction in allergic symptoms during a TNPT. In addition, safety analysis revealed a good tolerability of both SLIT extracts.

Keywords: Birch pollen allergy; Nasal provocation test (NPT); Non-inferiority design; Randomized; Sublingual immunotherapy (SLIT).

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Figures

Figure 1
Figure 1
Disposition of patients.
Figure 2
Figure 2
Mean symptom scores following TNPT before and after treatment with SUB-B B (ITT population, n = 36). The 10,000 AU/ml challenge was only given during the 2nd TNPT if the challenge at 1,000 AU/ml was negative.
Figure 3
Figure 3
Mean symptom scores following TNPT before and after treatment with Stal-B (ITT population, n = 35). The 10,000 AU/ml challenge was only given during the 2nd TNPT if the challenge at 1,000 AU/ml was negative.
Figure 4
Figure 4
Bet v and Bet v 1 specific IgE levels (including standard error) before and after SLIT treatment. No significant differences in the increase in Bet v (p = 0.62) and Bet v 1 (p = 0.63) specific IgE levels was observed following SUB-B and Stal-B treatment.
Figure 5
Figure 5
Bet v specific IgG levels (including standard error) before and after SLIT treatment. Bet v specific IgG levels increased in both groups, the increase in the SUB-B groups was significantly higher than in the Stal-B group (p = 0.03).
Figure 6
Figure 6
Bet v and Bet v1 specific IgG4 levels (including standard error) before and after SLIT treatment. No significant differences in the increase in Bet v (p = 0.17) and Bet v 1 (p = 0.11) specific IgG4 levels was observed following SUB-B and Stal-B treatment.
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