Disease-Modifying Effect of Japanese Cedar Pollen Sublingual Immunotherapy Tablets.

BACKGROUND: Japanese cedar (JC) pollinosis is a common allergic rhinitis in Japan. JC pollen sublingual immunotherapy (SLIT) tablets are licensed for the treatment of JC pollinosis. OBJECTIVE: To assess the disease-modifying effects of JC pollen SLIT tablets over 5 years (2014-2019), comprising a 3-year treatment period and 2-year follow-up. METHODS: A total of 1042 patients with JC pollinosis (aged 5-64 years) were included in the study. An optimal dose-finding study was performed in the first 15 months, after which 240 patients in the placebo (P) group and 236 patients in the optimal active dose (A) group (5000 Japanese allergy units) were re-randomized to receive P or A for an additional 18 months (designated AA, AP, PA, and PP groups). Clinical efficacy was evaluated by the total nasal symptom and medication score (TNSMS) during the peak symptom period of each JC pollen season over 3 years of treatment and 2 years of observation after treatment cessation. RESULTS: The AA, AP, and PA groups exhibited significantly reduced TNSMS; however, the largest relative reduction was seen in the AA group both during the treatment period (third season, 46.3% vs PP, P < .001) and during the 2-year follow-up period (fourth and fifth seasons, 45.3% and 34.0% vs PP, respectively; P < .001). The most common adverse drug reactions were mild reactions at the administration site. CONCLUSIONS: JC pollen SLIT tablets show sustained clinical efficacy during 3 years of treatment and sustained disease-modifying effects for at least 2 years after treatment cessation.

Long-term treatment of Japanese cedar pollinosis with Japanese cedar pollen SLIT drops and persistence of treatment effect: A post-marketing clinical trial.

BACKGROUND: There have been no reports of treatment effect persistence after long-term sublingual immunotherapy (SLIT) in patients with Japanese cedar (JC) pollinosis. Therefore, we conducted a post-marketing clinical trial to investigate the efficacy, safety, and effect persistence of JC pollen SLIT drops after approximately 3 years of treatment. METHODS: This was an open-label trial of 233 patients with JC pollinosis who were treated with JC pollen SLIT drops for approximately 3 years (2015-2017) and followed-up for an additional 2 years (2018-2019). Efficacy and effect persistence were evaluated using nasal and ocular symptom scores, daily use of rescue medication, and Japanese Rhinoconjunctivitis Quality of Life Questionnaire scores recorded during the JC pollen dispersal season of each year. Safety was evaluated by monitoring adverse events and adverse drug reactions. RESULTS: The mean combined total nasal symptom and medication score (range 0-18) during the peak symptom periods of 2015 through 2019 were 5.47 ± 3.38, 4.52 ± 3.13, 3.58 ± 2.63, 5.28 ± 4.01, and 6.83 ± 4.65, respectively. The percentage of patients who used no rescue medications during the same periods was 64.8%, 75.2%, 80.3%, 63.7%, and 50.3%, respectively. A total of 138 adverse drug reaction incidents were recorded in 73 of the 233 patients (31.3%), of which 134 incidents (97.1%) were mild in severity. CONCLUSIONS: JC pollen SLIT drops demonstrated treatment duration-dependent efficacy with effects that persisted for 2 years after cessation of treatment. The drug had a favorable safety profile over the 5-year study period.

Safety profile and immunological response of dual sublingual immunotherapy with house dust mite tablet and Japanese cedar pollen tablet.

BACKGROUND: There have been no studies of dual administration of sublingual immunotherapy (SLIT) tablets for perennial and seasonal allergic rhinitis. This trial (JapicCTI-184014) was conducted to investigate the safety profile and immunological response during dual therapy with SQ house dust mite (HDM) and Japanese cedar pollen (JCP) SLIT tablets. METHODS: This was a multicenter, open-label, randomized trial of 109 Japanese patients with coexisting HDM and JCP allergic rhinitis who had positive tests for HDM- and JCP specific IgE (≥0.7 kU/L). Patients were allocated to receive HDM (N = 54) or JCP (N = 55) SLIT tablets alone for 4 weeks followed by 8 weeks of dual therapy with both SLIT tablets administered within 5 min of each other. Adverse events (AEs), adverse drug reactions (ADRs), and serum IgE and IgG4 specific for HDM (Dermatophagoides farinae, Dermatophagoides pteronyssinus) and JCP were recorded. RESULTS: The percentage of subjects with AEs and ADRs was similar between the two groups and between the two periods of monotherapy and dual therapy. Most AEs and ADRs were mild in severity, and no serious events were observed. The most common ADRs were local events in the oral cavity. Levels of IgE and IgG4 specific for HDM (D. farinae, D. pteronyssinus) and JCP were increased after treatment with HDM and JCP SLIT tablets, respectively. CONCLUSIONS: Dual therapy with both SLIT tablets administered within 5 min after 4 weeks of monotherapy with HDM or JCP tablet was well tolerated and induced the expected immunological responses.

Treatment duration-dependent efficacy of Japanese cedar pollen sublingual immunotherapy: Evaluation of a phase II/III trial over three pollen dispersal seasons.

BACKGROUND: We conducted a randomized, placebo-controlled, double-blind clinical trial to investigate the optimal dose and long-term efficacy and safety of Japanese cedar (JC) pollen tablets for SLIT (JapicCTI-142579). Here, we report details of the effects of the JC pollen SLIT tablet on rhinitis and conjunctivitis symptoms over three pollen dispersal seasons. METHODS: A total of 1042 JC pollinosis patients (aged 5-64 years) were randomized to receive tablets containing placebo (P), 2000, 5000, or 10,000 Japanese allergy units (JAU) of JC pollen for 15 months to identify an optimal dose. Patients receiving P (n = 240) and the optimal dose (5000 JAU; A, n = 236) were then randomized to receive P or A for an additional 18 months (AA, AP, PA, and PP groups, allocation ratio 2:1:1:2). Nasal and ocular symptoms, rescue medication use, and quality of life (QOL) were assessed on quantitative scales. RESULTS: In the second and third seasons, the AA, AP, and PA groups exhibited significantly better improvements in nasal, ocular, and medication scores compared with the PP group in the order AA > AP > PA > PP during the second season and AA > PA > AP > PP during the third season. Rescue medication use and QOL scores were also significantly better in the AA, AP, and PA groups compared with the PP group. CONCLUSIONS: The JC pollen SLIT tablet relieved nasal and ocular symptoms and medication use and improved QOL in a treatment duration-dependent manner. Continuous dosing regimens appear to enhance the efficacy of the drug.

Long-Term Efficacy and Dose-Finding Trial of Japanese Cedar Pollen Sublingual Immunotherapy Tablet.

BACKGROUND: Japanese cedar (JC) pollinosis is a common allergic rhinitis in Japan. The JC pollen sublingual immunotherapy (SLIT) tablet was developed using the highest concentration of JC pollen extract. OBJECTIVE: This was a randomized, double-blind, placebo-controlled phase II/III trial to investigate the optimal dose of the JC pollen SLIT tablet and examine long-term efficacy and safety for 3 years with the selected dose, and 2-year follow-up. METHODS: A total of 1042 patients with JC pollinosis (aged 5-64 years) were equally randomized into 4 groups and received daily treatment with 2,000, 5,000, or 10,000 Japanese allergy unit (JAU) or placebo. The primary end point was the total nasal symptom and medication score (TNSMS) during the peak symptom period in the first season. Key secondary end points were TNSMS for the JC pollen dispersion season and total nasal and ocular symptom and medication score for the peak symptom period and JC pollen dispersion season. RESULTS: For the primary end point, absolute reductions and relative mean reductions in TNSMS compared with placebo were 1.50 and 21.4%, 2.24 and 32.1%, and 2.18 and 31.2% for 2,000, 5,000, and 10,000 JAU, respectively (P < .001 in all groups). For all key secondary end points, efficacy was confirmed for all doses (P < .001 in all groups). The treatment was well tolerated. Long-term efficacy of 5,000 JAU was shown over the 3 years. CONCLUSIONS: The optimal dose of the JC pollen SLIT tablet was 5,000 JAU, with good efficacy and safety over a 3-year treatment period. This sustained effect was dependent on treatment duration.

[INVESTIGATION OF TREATMENT GOAL IN ALLERGEN IMMUNOTHERAPY FOR JAPANESE CEDAR POLLINOSIS].

BACKGROUND/OBJECTIVE: As few reports are available on treatment goal for Japanese cedar pollinosis treated with allergen immunotherapy, therapeutic effect has to be assessed based on subjective symptoms in clinical practice. This research was conducted to investigate the informative treatment goal in clinical practice by using the results of TO-194SL phase III clinical trial. METHODS: In this investigation, correlation between total nasal symptom medication score (TNSMS), which was predefined as the primary endpoint, and secondary endpoints evaluated by severe symptom day, quality of life (QOL) score, and overall evaluation by subject, was firstly investigated. Based on the results, stratified analyses of the secondary endpoints to confirm relationships on the stratified results, TNSMS, and cedar season were performed. RESULTS: Correlation between TNSMS and evaluations which were severe symptom day, QOL score, and overall evaluation by subject was reasonably observed. TNSMS generally showed 3 or below (classified as mild) throughout the entire pollen season when these evaluations reached each threshold. CONCLUSIONS: The results of this investigation suggest that a few evaluation items would help patients to realize the therapeutic effects of allergen immunotherapy if they could be the treatment goal in clinical practice.

The Relationship of Pollen Dispersal with Allergy Symptoms and Immunotherapy: Allergen Immunotherapy Improves Symptoms in the Late Period of Japanese Cedar Pollen Dispersal.

BACKGROUND: The severity of symptoms of pollen-induced allergic rhinitis is affected by the amount of scattered pollen. However, the relationships between the pollen dispersal pattern, symptom severity, and treatment efficacy are not clear. METHODS: Between 2007 and 2012, we performed 4 randomized, placebo-controlled studies of sublingual immunotherapy (SLIT) on patients with Japanese cedar-induced allergic rhinitis who lived in or around Chiba, Japan. The participants were asked to avoid using rescue medicines during the cedar pollen season as much as possible and to record their nasal symptoms in allergy diaries. The amount of pollen dispersed daily was quantified using the Durham method, and the season was divided into early and late periods based on the pollen count. RESULTS: A total of 721 patients were enrolled in the 4 studies during the 6-year study period. In the placebo group (n = 349), a correlation was observed between the amount of pollen dispersed and the severity of symptoms in the early but not late period of pollen dispersal. Treatment with SLIT (n = 372) significantly improved symptom severity in the late but not early period. CONCLUSION: For patients with Japanese cedar pollen-induced allergic rhinitis, the fluctuation of daily pollen dispersal had a minimal effect on the severity of symptoms during the late period. SLIT was remarkably effective in alleviating symptoms during this period but not in the early period.

An analysis of factors related to the effect of sublingual immunotherapy on Japanese cedar pollen induced allergic rhinitis.

BACKGROUND: Sublingual immunotherapy (SLIT) can improve the symptoms of allergic rhinitis and modify its natural history; however, its efficacy varies among patients. This study aimed to determine which factors modify the effect of SLIT through post hoc analysis of a previous phase 3 trial of standardized Japanese cedar (JC) pollen extract (CEDARTOLEN®). METHODS: The study included 482 patients who had previously completed a phase 3 trial during two seasons. The SLIT and placebo groups each contained 241 subjects. Because pollen dispersal differed in the two seasons, we identified good and poor responders from the SLIT group in the 2nd season. We compared patient baseline characteristics, changes in serum immunoglobulin, and severity of symptoms in the 1st season between good and poor responders, as well as between SLIT and placebo groups. RESULTS: When we compared the baseline characteristics of good and poor responders, a significant difference was observed in body mass index (BMI) such that the patients with BMI ≥25 presented with lower treatment efficacy. No significant difference was observed in correlation with any other factors or treatment-induced alterations of serum immunoglobulin levels. We found that 75.3% of the patients with moderate symptoms and 50.9% of the patients with severe or very severe symptoms in the 1st season met our criteria for good responders in the 2nd season. CONCLUSIONS: BMI might modify the effect of SLIT; however, other factors were not related clearly. The severity of symptoms in the 1st season of treatment does not predict that in the 2nd season.

Efficacy and safety of sublingual immunotherapy for two seasons in patients with Japanese cedar pollinosis.

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.

Mental health survey of truck drivers.

OBJECTIVES: The health management of truck drivers has long been considered extremely important from the perspective of prevention of diseases and traffic accidents. Today, truck drivers may have various underlying health problems, including psychological burden caused by deregulation with the enforcement of the Trucking Business Act, rising fuel costs, and even economic stagnation. In this study, we investigated the mental health of individuals working in transportation and logistics sectors, which ensures the secure supply and sound development of safe and high-quality transportation services. METHODS: To ascertain the mental health status in this population, we used the General Health Questionnaire (GHQ30), an assessment of mental health and currently the general health questionnaire most widely used by the department of psychosomatic medicine and other clinical departments. RESULTS: Although the mean GHQ30 score of all the subjects in this study was below the cutoff point of 6-7, which separates individuals with mental health problems from those who without 30% of the subjects were classified as having mental health problems, revealing the need for routine screening of the mental health status and severity of symptoms of truck drivers. CONCLUSIONS: There is growing recognition of the importance of establishing mental healthcare services in the workplace because of the sharply increasing number of applications for workers' compensation due to suicides from overwork. In this study, 16.7% of truck drivers expressed suicidal thoughts, indicating that it is necessary to conduct follow-up surveys of the mental conditions of truck drivers in order to put in place appropriate mental health measures.