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. AIMS OF THE STUDY: 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.

Prolonged preseasonal treatment phase with Grazax sublingual immunotherapy increases clinical efficacy.

BACKGROUND: Sublingual immunotherapy treatment with grass allergen tablets (Grazax) is initiated preseasonally without up-dosing and treatment is continued throughout the entire grass pollen season. AIMS OF THE STUDY: The influence of the duration of preseasonal treatment on clinical efficacy obtained within the grass pollen season was investigated. METHODS: Data from three randomized, double-blind, placebo-controlled, multi-centre trials with varying preseasonal treatment periods were analysed. In the grass pollen season, symptom and medication score reductions relative to placebo were calculated and correlated with the duration of the preseasonal treatment period. RESULTS: The analysis was based on data from 934 patients. A significant reduction in seasonal daily rhinoconjunctivitis symptom and medication scores (17%, CI: 1-33% and 23%, CI: 1-47%, P < 0.05) was observed for patients treated with Grazax compared with placebo after approximately 8 weeks of pretreatment. The magnitude of the reductions in rhinoconjunctivitis symptom and medication scores increased with longer duration of preseasonal treatment (P < 0.0001). CONCLUSIONS: Sublingual immunotherapy with Grazax) must be initiated at least 8 weeks prior to the grass pollen season to provide a significant clinical efficacy. A longer preseasonal treatment period (>8 weeks) improves the clinical efficacy (relative to placebo) during the grass pollen season.