Background: Japanese cedar (JC) pollinosis is the most common seasonal allergic rhinitis in Japan. Standardized JC pollen extract is available for subcutaneous immunotherapy, but this treatment is limited by potentially serious side effects. The aim of this double-blind, randomized comparative study was to evaluate the efficacy and safety of standardized JC pollen extract in a new oral formulation (CEDARTOLEN®, Torii Pharmaceutical Co., Ltd., Tokyo, Japan) for sublingual immunotherapy (SLIT) for JC pollinosis. Methods: A total of 531 subjects with JC pollinosis were randomized into 2 groups at a ratio of 1:1 to receive daily sublingual administration of standardized JC pollen extract with a maintenance dose of 2,000 Japanese allergy units (JAU) or placebo for 2 consecutive pollen seasons. The efficacy was evaluated using the total nasal symptom and medication score (TNSMS) as the primary end point. Secondary end points included the total ocular symptom and medication score (TOSMS) and scores for individual symptoms and medication. Results: The TNSMS was significantly lower (p < 0.0001) in the SLIT group than in the placebo group in the peak symptom period by 18 and 30% in the first and second seasons, respectively. All secondary end points were also significantly lower in the SLIT group in both seasons. No systemic anaphylaxis occurred. Conclusions: SLIT with daily administration of standardized JC pollen extract was effective for improving nasal and ocular symptoms of JC pollinosis and reducing the use of relief medication. The JC pollen extract was well tolerated with only local adverse events.

Keywords:
Japanese cedar pollinosis, Pollen extract, Seasonal allergic rhinitis, Sublingual immunotherapy
1.
Okamoto Y, Horiguchi S. Yonekura S, Yamamoto H, Hanazawa T: Present situation of cedar pollinosis in Japan and its immune responses. Allergol Int 2009;58:152-162.
2.
Okuda M: Epidemiology of Japanese cedar pollinosis throughout Japan. Ann Allergy Asthma Immunol 2003;91:288-296.
3.
Ozasa K, Dejima K, Takenaka H: Prevalence of Japanese cedar pollinosis in Japanese school children. Int Arch Allergy Immunol 2002;128:165-167.
4.
Sakashita M, Hirota T, Harada M, Nakamichi R, Tsunoda T, Osawa Y, Kojima A, Okamoto M, Suzuki D, Kubo S, Imoto Y, Nakamura Y, Tamari M, Fujieda S: Prevalence of allergic rhinitis and sensitization to common aeroallergens in a Japanese population. Int Arch Allergy Immunol 2010;151:255-261.
5.
Yonekura S, Okamoto Y, Horiguchi S, Sakurai D, Chazono H, Hanazawa T, Aoki S, Konno A: Effect of aging on the natural history of seasonal allergic rhinitis in middle-aged subjects in south Chiba, Japan. Int Arch Allergy Immunol 2012;157:73-80.
6.
Fujieda S, Kurono Y, Okubo K, Ichimura K, Enomoto T, Kawauchi H, Masuyama K, Goto M, Suzuki H, Okamoto Y, Takenaka H: Examination, diagnosis and classification for allergic rhinitis: Japanese guideline. Auris Nasus Larynx 2012;39:553-556.
7.
Bernstein DI, Wanner M, Borish L, Liss GM; Immunotherapy Committee, American Academy of Allergy, Asthma and Immunology: Twelve-year survey of fatal reactions to allergen injections and skin testing: 1990-2001. J Allergy Clin Immunol 2004;113:1129-1136.
8.
Durham SR, Emminger W, Kapp A, de Monchy JG, Rak S, Scadding GK, Wurtzen PA, Andersen JS, Tholstrup B, Riis B, Dahl R: SQ-standardized sublingual grass immunotherapy: confirmation of disease modification 2 years after 3 years of treatment in a randomized trial. J Allergy Clin Immunol 2012;129:717-725.
9.
Didier A, Worm M, Horak F, Sussman G, de Beaumont O, Le Gall M, Melac M, Malling HJ: Sustained 3-year efficacy of pre- and coseasonal 5-grass-pollen sublingual immunotherapy tablets in patients with grass pollen-induced rhinoconjunctivitis. J Allergy Clin Immunol 2011;128:559-566.
10.
Nelson HS, Nolte H, Creticos P, Maloney J, Wu J, Bernstein DI: Efficacy and safety of Timothy grass allergy immunotherapy tablet treatment in North American adults. J Allergy Clin Immunol 2011;127:72-80.
11.
Cox LS, Casale TB, Nayak AS, Bernstein DI, Creticos PS, Ambroisine L, Melac M, Zeldin RK: Clinical efficacy of 300IR 5-grass pollen sublingual tablet in US study. J Allergy Clin Immunol 2012;130:1327-1334.
12.
Horiguchi S, Okamoto Y, Yonekura S, Okawa T, Yamamoto H, Kunii N, Sakurai D, Fujimura T, Nakazawa K, Yasueda H: A randomized controlled trial of sublingual immunotherapy for Japanese cedar pollinosis. Int Arch Allergy Immunol 2008;146:76-84.
13.
Okubo K, Gotoh M, Fujieda S, Okano M, Yoshida H, Morikawa H, Masuyama K, Okamoto Y, Kobayashi M: A randomised double-blind comparative study of sublingual immunotherapy for cedar pollinosis. Allergol Int 2008;57:265-275.
14.
Fujimura T, Yonekura S, Horiguchi S, Taniguchi Y, Saito, A, Yasueda H, Inamine A, Nakayama T, Takemori T, Taniguchi M, Sakaguchi M, Okamoto Y: Increase of regulatory T cells and the ratio of specific IgE to total IgE are candidates for response monitoring or prognostic biomarkers in two-year sublingual immunotherapy (SLIT) for Japanese cedar pollinosis. Clin Immunol 2011;139:65-74.
15.
Durham OC: The volumetric incidence of atmospheric allergens; a proposed standard method of gravity sampling, counting, and volumetric interpolation of results. J Allergy 1946;17:79-86.
16.
Okuda M, Ohkubo K, Goto M, Okamoto H, Konno A, Baba K, Ogino S, Enomoto M, Imai T, So N, Ishikawa Y, Takenaka Y, Manndai T, Crawford B: Comparative study of two Japanese rhinoconjunctivitis quality-of-life questionnaires. Acta Otolaryngol 2005;125:736-744.
17.
Okuda M, Okubo K, Gotoh M, Okamoto Y, Imano A, Baba K, Ogino T, Ishikawa K, Takenata Y, So N, Imai T, Enomoto M, Mandai T, Crawford B: Standard questionnaire for QOL of Japanese patients with allergic rhinitis. Arerugi 2003;52(suppl 1):21-56.
18.
Sasaki K, Okamoto Y, Yonekura S, Okawa T, Horiguchi S, Chazono H, Hisamitsu M, Sakurai D, Hanazawa T, Okubo K: Cedar and cypress pollinosis and allergic rhinitis: quality of life effects of early intervention with leukotriene receptor antagonists. Int Arch Allergy Immunol 2009;149:350-358.
19.
Dahl R, Kapp A, Colombo G, de Monchy JG, Rak S, Emminger W, Rivas MF, Ribel M, Durham SR: Efficacy and safety of sublingual immunotherapy with grass allergen tablets for seasonal allergic rhinoconjunctivitis. J Allergy Clin Immunol 2006;118:434-440.
20.
Pajno GB, Caminiti L, Crisafulli G, Vita D, Valenzise M, De Luca R, Passalacqua G: Direct comparison between continuous and coseasonal regimen for sublingual immunotherapy in children with grass allergy: a randomized controlled study. Pediatr Allergy Immunol 2011;22:803-807.
21.
Stelmach I, Kaluzinska-Parzyszek I, Jerzynska J, Stelmach P, Stelmach W, Majak P: Comparative effect of pre-coseasonal and continuous grass sublingual immunotherapy in children. Allergy 2012;67:312-320.
22.
Didier A, Malling HJ, Worm M, Horak F, Jäger S, Montagut A, André C, de Beaumont O, Melac M: Optimal dose, efficacy, and safety of once-daily sublingual immunotherapy with a 5-grass pollen tablet for seasonal allergic rhinitis. J Allergy Clin Immunol 2007;120:1338-1345.
23.
Di Lorenzo G, Mansueto P, Oacor ML, Rizzo M, Castello F, Martinelli N, Ditta V, Lo Bianco C, Leto-Barone MS, D'Alcamo A, Di Fede G, Rini GB, Ditto AM: Evaluation of serum s-IgE/ total IgE ratio in predicting clinical responses to allergen-specific immunotherapy. J Allerg Clin Immunol 2009;123:1103-1110.
24.
Canonica GW, Bousquet J, Casale T, Lockey RF, Baena-Cagnani CE, Pawanker R, et al: Sub-lingual immunotherapy: World Allergy Organization position paper 2009. World Allergy Organ J 2009;2:233-281.
25.
Bousquet J, Lockey R, Malling HJ: Allergen immunotherapy: therapeutic vaccines for allergic diseases. A WHO position paper. J Allergy Clin Immunol 1998;102:558-562.
26.
Durham SR, Emminger W, Kapp A, de Monchy JG, Rak S, Scadding GK, Wurtzen PA, Andersen JS, Tholstrup B, Riis B, Dahl R: SQ-standardized sublingual grass immunotherapy: confirmation of disease modification 2 years after 3 years of treatment in a randomized trial. J Allergy Clin Immunol 2012;129:717-725.
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2015
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