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Efficacy and safety of birch pollen allergoid subcutaneous immunotherapy: A 2‐year double‐blind, placebo‐controlled, randomized trial plus 1‐year open‐label extension
Author(s) -
Worm Margitta,
Rak Sabina,
Samoliński Boleslaw,
Antila Jukka,
Höiby AnnSofi,
Kruse Brigitte,
Lipiec Agnieszka,
Rudert Michael,
Valovirta Erkka
Publication year - 2019
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1111/cea.13331
Subject(s) - medicine , clinical endpoint , placebo , randomized controlled trial , allergen immunotherapy , allergy , clinical trial , intention to treat analysis , gastroenterology , allergen , surgery , immunology , alternative medicine , pathology
Summary Background Previous clinical trials with birch pollen subcutaneous immunotherapy have been conducted over a 1‐ to 2‐year treatment period and involved mostly a single geographic location. Objective This study (EudraCT‐Number: 2005‐000025‐35) intended to evaluate the effect of subcutaneous immunotherapy with high‐dose hypoallergenic birch pollen allergoid in patients with confirmed moderate to severe seasonal allergic rhinitis/rhinoconjunctivitis over a 3‐year course in 19 European centres. Methods Adults with confirmed birch pollen allergy (n = 253) were randomized to preseasonal placebo (n = 129) or active treatment (n = 124). Primary endpoint was change in Symptom Medication Score after 2 years treatment (2007). Results The change in Symptom Medication Score of active‐ vs placebo‐treated patients for the Full Analysis Set (n = 227, 15.2% reduction, P = 0.0710) and Per‐Protocol Set (n = 216, 16.7% reduction, P = 0.0523) showed a positive trend, although significance was not achieved. The primary endpoint, assessed in 2007, coincided with the lowest pollination during the study period. In a subgroup analysis of patients in the north‐eastern region (n = 102), where birch is the major tree and consequently patients’ exposure is higher, changes in Symptom Medication Score (32.7% reduction, P = 0.0034) and median number of well days ( P = 0.0232) were highly significant in favour of the active group. During the open‐label third year of treatment, the mean Symptom Medication Score of active‐treated patients was further reduced despite an increased pollen count. Subcutaneous immunotherapy was well tolerated and consistent with the known safety profile. Conclusions and clinical relevance Although the primary endpoint was not reached for the Full Analysis Set, a significant and clinically relevant effect on Symptom Medication Score was clearly demonstrated for the subgroup of patients in the north‐eastern region of Europe, where birch is the predominant tree species. Proving efficacy of birch allergen subcutaneous immunotherapy is challenging due to the numerous factors influencing birch pollen allergen exposure in field studies.