Allergy immunotherapy with a hypoallergenic recombinant birch pollen allergen rBet v 1-FV in a randomized controlled trial

Ludger Klimek, Claus Bachert, Karl-Friedrich Lukat, Oliver Pfaar, Hanns Meyer, Annemie Narkus, Ludger Klimek, Claus Bachert, Karl-Friedrich Lukat, Oliver Pfaar, Hanns Meyer, Annemie Narkus

Abstract

Background: Pollen extracts and chemically modified allergoids are used successfully in allergen immunotherapy (AIT). Recombinant extracts offer potential advantages with respect to pharmaceutical quality, standardization and dosing. A hypoallergenic recombinant folding variant of the major birch pollen allergen (rBet v 1-FV) was compared with an established native birch preparation. A pre-seasonal, randomized, actively controlled phase II study was performed in birch pollen allergic rhino-conjunctivitis with or without asthma, GINA I/ II. 51 patients (24 rBet v 1-FV, 27 native extract) started therapy with subcutaneous allergen immunotherapy (SCIT). Primary end-point was a combined symptom medication score (SMS), changes in nasal provocation test, visual rating score and specific antibody responses secondary end-points.

Findings: After one pre-seasonal treatment course the combined SMS was 5.86 (median; IQR: 14.02) for the rBet v 1-FV group versus 12.40 (median; IQR: 9.32) for the comparator during the three weeks pollen season (p = 0.330). After treatment in the second year, scores were 3.00 (median; IQR: 6.50) and 2.93 (4.86) respectively. Allergen tolerance in a nasal provocation test improved to a comparable extent in both groups. Significant increases in birch pollen-specific IgG1 and IgG4 were observed in both treatment groups following the first treatment phase and remained significantly raised until the end of the study.

Conclusion: In this first in man, proof of concept phase II trial no statistical difference between rBet v 1-FV and an established natural pollen extract could be observed. rBet v 1-FV could be administered in higher doses than the native protein with no increase in adverse effects.

Trial registration: The study was registered in clinicalTrials.gov (NCT00266526).

Keywords: Allergic rhinitis; Allergy immunotherapy; Birch pollen; Folding variant; Hypoallergenic variant; Recombinant Bet v 1; Recombinant allergen; Rhino-conjunctivitis; Subcutaneous immunotherapy.

Figures

Fig. 1
Fig. 1
Flow chart documenting progress through the study of those patients included in the main data sets
Fig. 2
Fig. 2
Course of daily median SMS and median pollen counts during the 21-day observational periods in the birch pollen season after one (above) and two courses (below) of SCIT, respectively
Fig. 3
Fig. 3
Birch pollen-specific IgE, IgG1 and IgG4 concentrations. Median values with 25th/75th and 10th/90th percentiles represented by boxes and error bars respectively, outliers by points. Time points: 1, screening before SCIT; 2, after up-dosing first year; 3, after pollen season first year; 4, after up-dosing second year; and 5, after pollen season second year

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