Evaluation of Montelukast for the Treatment of Children With Japanese Cedar Pollinosis Using an Artificial Exposure Chamber (OHIO Chamber)

Kazuhiro Hashiguchi, Kimihiro Okubo, Yoichi Inoue, Hirotaka Numaguchi, Kumi Tanaka, Nobuyuki Oshima, Anish Mehta, Chisato Nishida, Itori Saito, George Philip, Kazuhiro Hashiguchi, Kimihiro Okubo, Yoichi Inoue, Hirotaka Numaguchi, Kumi Tanaka, Nobuyuki Oshima, Anish Mehta, Chisato Nishida, Itori Saito, George Philip

Abstract

Background: This study evaluated the efficacy of montelukast in reducing seasonal allergic rhinitis symptoms in Japanese children with Japanese cedar (JC) pollinosis induced in an artificial exposure chamber (OHIO Chamber).

Methods: Pediatric patients aged 10 to 15 years sensitive to JC pollen entered a randomized, double-blind, single-site, crossover study. After confirmation of an allergic response to a JC pollen exposure for 3 hours in the OHIO Chamber during the screening period, subjects received either montelukast 5 mg chewable tablets or placebo for a 7-day treatment period, followed by a 3-hour pollen exposure in the chamber. After a 7-day washout period, subjects crossed over to the other treatment. Subjects were instructed to self-assess their nasal symptoms using 5-point scale for every 30 minutes. The primary end point was the change from baseline (just before entering the exposure chamber for each exposure) in total nasal symptom score (TNSS; the sum of nasal congestion, nasal discharge, and sneezing scores) over 3 hours of pollen exposure. Adverse events (AEs) were evaluated throughout the study.

Results: A total of 220 subjects (median age, 12 years) received treatment. For TNSS, the between-group difference in the change (95% confidence interval) was -0.01 (-0.11 to 0.10); the change between placebo and montelukast 5 mg was not significant. TNSS in the screening and treatment periods after receiving placebo for 7 days was 1.58 and 1.31, respectively, suggesting a placebo response. On account of high placebo response, a post hoc analysis was conducted. The analysis in a subgroup of subjects who did not show placebo response demonstrated a difference in the efficacy between montelukast and placebo (nominal P < .037). The most common AE was positive urine protein (4.6% with montelukast vs 7.8% with placebo).

Conclusions: Although montelukast was well tolerated, this study did not demonstrate a treatment difference between active drug and placebo in Japanese children exposed to JC pollen in the OHIO Chamber.Trial Registry: ClinicalTrials.gov, NCT01852812.

Trial registration: ClinicalTrials.gov NCT01852812 NCT01857063.

Keywords: Japanese cedar pollinosis; OHIO Chamber; montelukast; nasal discharge eosinophils; pediatric patient.

Figures

Figure 1.
Figure 1.
Study design.
Figure 2.
Figure 2.
Disposition of subjects.
Figure 3.
Figure 3.
Efficacy summary: change from placebo for primary end point (mean TNSS over 3 h) and subgroup analyses by age and for patients who did not exhibit a placebo effect (FAS population). Based on longitudinal data analysis model with baseline TNSS as a covariate, sequence, treatment, and period as fixed effects and subject as a random effect. The values in P for post hoc subgroup analyses were nominal because they were not adjusted for multiplicity. FAS, full analysis set. *No clinically important difference (ie, change in 1 point on 6-point TNSS scale) between the screening placebo run-in period and the placebo sequence of the treatment period.

References

    1. Blaiss MS. Pediatric allergic rhinitis: physical and mental complications. Allergy Asthma Proc. 2008; 29(1):1–6.
    1. Borres MP. Allergic rhinitis: more than just a stuffy nose. Acta Paediatr. 2009; 98(7):1088–1092.
    1. Mir E, Panjabi C, Shah A. Impact of allergic rhinitis in school going children. Asia Pac Allergy. 2012; 2(2):93–100.
    1. Yuksel H, Sogut A, Yilmaz H, Yilmaz O, Dinc G. Sleep actigraphy evidence of improved sleep after treatment of allergic rhinitis. Ann Allergy Asthma Immunol. 2009; 103(4):290–294.
    1. Okubo K, Kurono Y, Ichimura K, et al. Japanese guidelines for allergic rhinitis 2017. Allergol Int. 2017; 66(2):205–219.
    1. Cingi C, Muluk NB, Ipci K, Sahin E. Antileukotrienes in upper airway inflammatory diseases. Curr Allergy Asthma Rep. 2015; 15(11):64.
    1. Haberal I, Corey JP. The role of leukotrienes in nasal allergy. Otolaryngol Head Neck Surg. 2003; 129(3):274–279.
    1. Yilmaz O, Altintas D, Rondon C, Cingi C, Oghan F. Effectiveness of montelukast in pediatric patients with allergic rhinitis. Int J Pediatr Otorhinolaryngol. 2013; 77(12):1922–1924.
    1. Figueroa DJ, Borish L, Baramki D, Philip G, Austin CP, Evans JF. Expression of cysteinyl leukotriene synthetic and signalling proteins in inflammatory cells in active seasonal allergic rhinitis. Clin Exp Allergy. 2003; 33(10):1380–1388.
    1. Peters-Golden M, Gleason MM, Togias A. Cysteinyl leukotrienes: multi-functional mediators in allergic rhinitis. Clin Exp Allergy. 2006; 36(6):689–703.
    1. Hashiguchi K, Tang H, Fujita T, et al. Validation study of the OHIO Chamber in patients with Japanese cedar pollinosis. Int Arch Allergy Immunol. 2009; 149(2):141–149.
    1. Hashiguchi K, Tang H, Fujita T, et al. Preliminary study on Japanese cedar pollinosis in an artificial exposure chamber (OHIO Chamber). Allergol Int. 2007; 56(2):125–130.
    1. Okubo K, Baba K. Therapeutic effect of montelukast, a cysteinyl leukotriene receptor 1 antagonist, on Japanese patients with seasonal allergic rhinitis. Allergol Int. 2008; 57(3):247–255.
    1. Okubo K, Baba K. A double-blind non-inferiority clinical study of montelukast, a cysteinyl leukotriene receptor 1 antagonist, compared with pranlukast in patients with seasonal allergic rhinitis. Allergol Int. 2008; 57(4):383–390.
    1. Philip G, Malmstrom K, Hampel FC, et al. Montelukast for treating seasonal allergic rhinitis: a randomized, double-blind, placebo-controlled trial performed in the spring. Clin Exp Allergy. 2002; 32(7):1020–1028.
    1. van Adelsberg J, Philip G, LaForce CF, et al. Randomized controlled trial evaluating the clinical benefit of montelukast for treating spring seasonal allergic rhinitis. Ann Allergy Asthma Immunol. 2003; 90(2):214–222.
    1. Chervinsky P, Philip G, Malice MP, et al. Montelukast for treating fall allergic rhinitis: effect of pollen exposure in 3 studies. Ann Allergy Asthma Immunol. 2004; 92(3):367–373.
    1. van Adelsberg J, Philip G, Pedinoff AJ, et al. Montelukast improves symptoms of seasonal allergic rhinitis over a 4-week treatment period. Allergy. 2003; 58(12):1268–1276.
    1. Wakabayashi K, Hashiguchi K, Kanzaki S, et al. Pranlukast dry syrup inhibits symptoms of Japanese cedar pollinosis in children using OHIO Chamber. Allergy Asthma Proc. 2012; 33(1):102–109.
    1. Biopharmaceutical Testing and Analysis of ONO-1078 Dry Syrup 10% Formulation. Ono Pharmaceutical. . Published 2011. Accessed June 5, 2018.
    1. Fujieda S, Kurono Y, Okubo K, et al. Examination, diagnosis and classification for Japanese allergic rhinitis: Japanese guideline. Auris Nasus Larynx. 2012; 39(6):553–556.
    1. Gotoh M, Okubo K, Hashiguchi K, et al. Noninvasive biological evaluation of response to pranlukast treatment in pediatric patients with Japanese cedar pollinosis. Allergy Asthma Proc. 2012; 33(6):459–466.
    1. Rondon C, Fernandez J, Canto G, Blanca M. Local allergic rhinitis: concept, clinical manifestations, and diagnostic approach. J Investig Allergol Clin Immunol. 2010; 20(5):364–371; quiz 2 p following 71.

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