Days with severe symptoms: an additional efficacy endpoint in immunotherapy trials.
BACKGROUND
In immunotherapy trials, primary and secondary endpoints often focus on average symptom and medication scores during the pollen season or on days with low symptoms and low medication use. Thus, there is a need for endpoints describing the treatment effect on the most troublesome days in the pollen season.


OBJECTIVE
A possible additional efficacy endpoint, days with severe symptoms during the pollen season, was investigated using data from a multicentre, double-blind, randomized, placebo-controlled trial of the SQ-standardized grass allergy immunotherapy tablet (AIT) (Grazax, Phleum pratense, 75,000 SQ-T/2,800 BAU, ALK, Hørsholm, Denmark).


METHODS
The trial included 634 subjects (N(Grass AIT) = 316; N(Placebo) = 318) with grass pollen-induced rhinoconjunctivitis. Six different definitions of a day with severe symptoms were suggested. The number of days with severe symptoms was analysed and odds ratios were calculated.


RESULTS
The number and percentage of days with severe symptoms differed between definitions, but overall the analysis of days with severe symptoms showed consistent results (odds ratios: 2.0-3.4) for the different definitions. All definitions showed a reduced risk of having days with severe symptoms in the grass AIT group when compared to the placebo group.


CONCLUSIONS
Days with severe symptoms during the pollen season is a relevant additional efficacy endpoint, which can be used in immunotherapy trials to support the clinical interpretation of commonly used efficacy endpoints.
Durham
S R
SR
Imperial College, National Heart and Lung Institute, London, UK.
Birk
A O
AO
Andersen
J S
JS
D000328:Adult; D003233:Conjunctivitis, Allergic / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology*; D004311:Double-Blind Method; D023381:Endpoint Determination; D005260:Female; D006801:Humans; D007167:Immunotherapy; D008297:Male; D031784:Phleum / Q000009:adverse effects / Q000276:immunology; D010936:Plant Extracts / Q000008:administration & dosage* / Q000627:therapeutic use; D011058:Pollen / Q000009:adverse effects / Q000276:immunology; D006255:Rhinitis, Allergic, Seasonal / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology*; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome
C551013:Grazax; D010936:Plant Extracts