A randomized, double-blind, placebo-controlled trial with mannan-conjugated birch pollen allergoids

被引:4
|
作者
Moesges, Ralph [1 ,2 ,10 ]
Zeyen, Christoph [2 ,3 ,4 ,5 ]
Raskopf, Esther [1 ]
Acikel, Cengizhan [1 ]
Sahin, Hacer [1 ]
Allekotte, Silke [1 ]
Cuevas, Mandy [6 ,7 ]
Shamji, Mohamed H. [8 ]
Subiza, Jose Luis [9 ]
Casanovas, Miguel [9 ]
机构
[1] ClinCompetence Cologne GmbH, Cologne, Germany
[2] Univ Cologne, Inst Med Stat & Computat Biol, Fac Med, Cologne, Germany
[3] Free Univ Berlin, Dept Dermatol Venereol & Allergol, Div Evidence Based Med dEBM, Berlin, Germany
[4] Humboldt Univ, Berlin, Germany
[5] Charite Univ Med Berlin, Berlin, Germany
[6] Tech Univ Dresden, Fac Med, Carl Gustav Carus Dept Otorhinolaryngol Head Neck, Dresden, Germany
[7] Tech Univ Dresden, Univ Hosp, Dresden, Germany
[8] Imperial Coll London, Allergy & Clin Immunol Sect, London, England
[9] Inmunotek SL, Madrid, Spain
[10] Clin Competence Cologne GmbH, Theodor Heuss Ring 14, D-50668 Cologne, Germany
关键词
allergic rhinoconjunctivitis; allergoid; birch pollen; combined symptom and medication score; mannan conjugate; DENDRITIC CELLS; NONOXIDIZED MANNAN; CLINICAL-TRIALS; IMMUNOTHERAPY; RHINOCONJUNCTIVITIS; ALLERGENS; MECHANISMS; ANTIBODIES; RESPONSES; EXTRACTS;
D O I
10.1111/all.15910
中图分类号
R392 [医学免疫学];
学科分类号
100102 ;
摘要
Background: There is still great need to develop new strategies to improve the efficacy of allergen immunotherapies with optimal safety standards for patients. A new promising approach is to couple allergoids to mannan. The objective of this phase IIa/IIb study was to identify the optimal dose of mannan-conjugated birch pollen allergoids for the short-course treatment of birch pollen-induced allergic rhinoconjunctivitis.Methods: For this prospective, randomized, double-blind, placebo-controlled, dose-finding study, 246 birch pollen-allergic adults received 0.5 mL placebo or 1000, 3000 or 10,000 mTU/mL of mannan-conjugated birch pollen allergoids at five pre-seasonal visits. Efficacy was assessed by comparing allergic rhinoconjunctivitis symptoms and use of anti-allergic medication during the peak of the birch pollen season 2020. Immunologic, tolerability and safety effects were also analysed.Results: The highest dose of mannan-conjugated birch pollen allergoids reduced the combined symptom and medication score during the peak birch pollen season by a median of 24.7% compared to placebo. The production of Bet v 1 specific IgG4 significantly increased in a dose-dependent manner (3.6- and 4.5-fold) in the 3000 and 10,000 mTU/mL groups. The Bet v 1 specific IgE/IgG4 ratio was also strongly reduced (up to -70%). No fatalities nor serious adverse events were reported, and no adrenaline was used. In total, four systemic reactions occurred (two grade I and two grade II).Conclusion: All doses of mannan-conjugated birch pollen allergoids can be considered as safe. Since the application of 10,000 mTU/mL resulted in the highest efficacy, this dose qualifies for further investigation.
引用
收藏
页码:990 / 1000
页数:11
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