Methods: This trial was carried out for two pollinosis seasons in 2007 and 2008 in double-blind status. Carry-over therapeutic effects were analyzed in 2009 in single-blind manner. We recruited 130 participants diagnosed as Japanese cedar pollinosis based on clinical history and the presence of IgE specific to Japanese cedar pollen of at least class 2. Cytokine production from peripheral blood mononuclear cells and increase of iTregs were determined before and after 2008 pollen season. Clinical symptoms were estimated using a pollinosis-symptom diary and Quality-of-Life (QOL) questionnaire in 2007, 2008, and 2009 peak pollen seasons.
Results: The final sample size included 88 subjects for on-treat analysis (SLIT; N=51, placebo; N=37) for the DBPC study, and a total of 63 patients completed a pollinosis-symptom diary for the single-blind follow-up study (SLIT; N=36, placebo; N=27). The symptom-medication score (SMS) in the SLIT group did not differ from that in the placebo group in the 2007 peak pollen season. However, the average SMS in 2008 and 2009 peak pollen seasons were significantly ameliorated in the SLIT group compared with the placebo group (4.2 vs. 5.3, P=0.02 in 2008; 3.5 vs. 4.5, P=0.03 in 2009). The ratio of Japanese cedar pollen-specific IgE to total IgE before treatment correlated with the SMS in the SLIT group in 2008. The patients with increased Cry j 1-specific iTregs in the SLIT group showed a significant reduction of QOL and QOL-symptom scores compared with those in the placebo group.
Conclusions: SLIT can ameliorate the clinical symptoms after 2-year administration with standardized extract of Japanese cedar pollen and the amelioration was observed for at least one pollen season after the treatment. The ratio of specific IgE to total IgE can be used as a prognostic biomarker and the increase of Cry j 1-specific iTregs may serve as a biomarker to monitor the clinical response to SLIT.