Sublingual Immunotherapy Group Research Articles

Efficacy of sublingual immunotherapy with dermatophagoides farinae drops in children with allergic rhinitis and the change of TGF-β and IL-13 mRNA level

Objective:The aim of this study is to evaluate the efficacy of sublingual immunotherapy (SLIT) with standardized dermatophagoides farinae drops and to examine the change of TGF-β and IL-13 mRNA level after 12 months SLIT in children with allergic rhinitis (AR). Method:Ninety-two children with AR were collected and randomly divided into two groups: SLIT group (n=62) and control group (n=30). Before and after SLIT for 6 months and 12 months, total nasal symptoms score (TNSS) and total medication score (TMS) were evaluated. In addition, the mRNA expression of TGF-β and IL-13 in peripheral blood mononuclear cells of AR children after immunotherapy were examined by qRT-PCR. Result:There were significant differences (P<0.01) in symptom and medication scores between the two groups after 12 months treatment. The patients in SLIT group had fewer symptoms and lower intake of medication.The rates for well controlled, partly controlled and uncontrolled children were 45.2%, 32.3% and 22.6%, respectively. Five children (5.4%) experienced local adverse events and 1 children (1.1%) experienced mild systemic adverse events. No severe adverse events happened during the treatment. Accordingly, comparing with the baseline value, the mRNA levels of TGF-β increased significantly, and IL-10 mRNA level decreased significantly in well controlled children after 12 months treatment. Conclusion:SLIT with dermatophagoides farinae drops is efficient and safe treatment for children with HDM induced AR. The change of TGF-β and IL-13 mRNA level may be considered as an indicator for evaluating the clinical efficacy of SLIT.

Clinical evaluation for sublingual immunotherapy with Dermatophagoides farinae drops in adult patients with allergic asthma.

The efficacy and safety of sublingual immunotherapy (SLIT) in house dust mite-induced allergic asthma (AA) have yet to be firmly established, especially in adult patients. Our objective is to evaluate the efficacy of SLIT with Dermatophagoides farinae drops in adult patients with AA. One hundred and thirty-four adult patient data with house dust mite (HDM)-induced AA who had been treated for 2years were collected. These patient data that we collected were divided into the SLIT group (n=85) and control group (n=49). All patients were treated with low to moderate dose of inhaled glucocorticoid and long-acting β2 agonists. Patients in the SLIT group were further treated with D. farinae drops. Clinical scores including the total asthma symptom score (TASS), total asthma medicine score (TAMS), asthma control test (ACT), and peak flow percentage (PEF%) were assessed before treatment and at yearly visits. The presence of adverse events (AEs) were recorded once a month. Before treatment, the PEF% in the SLIT group was significantly lower than that in the control group (p<0.05). After 2years, both treatments were effective in the clinical scores when compared with baseline values (all p<0.001). Meanwhile, the SLIT group showed significantly lower TASS and TAMS (all p<0.001) and higher ACT (p<0.001) and PEF% (p<0.05) when compared with the control group. No severe systemic AEs were reported. SLIT with D. farinae drops plus pharmacotherapy is more effective than routine drug treatment in adult patients with AA.

Could Sublingual Immunotherapy Affect Oral Health in Children with Asthma and/or Allergic Rhinitis Sensitized to House Dust Mite?

Background: Sublingual immunotherapy (SLIT) has been successfully employed in IgE-mediated respiratory allergies. However, it is not known whether the modulation of immune responses in the sublingual area during SLIT has any deleterious effect on oral health. We sought to determine the oral health prospectively in children receiving SLIT for house dust mite allergy. Material and Methods: Eighteen children with allergic asthma and/or rhinitis and 31 age-matched healthy controls (HC) were included in an open-labeled trial. Oral health was evaluated by scoring the decayed, missing, and filled teeth for primary (dmft) and permanent (DMFT) dentition, and the plaque and gingival indices. Moreover, cariogenic food intake and teeth-brushing habits were also noted at baseline and at 19 months. Results: The mean age of the SLIT participants was 9.5 ± 3.1 years and that of the HC was 9.2 ± 3.7 years. The mean duration of SLIT was 19.13 ± 3.81 months. At baseline, the total dmft and DMFT indices were similar in the SLIT and HC groups (p > 0.05), which demonstrated poor hygiene overall. In the within-group comparisons at the examination at 19 months, the SLIT group had a lower number of carious primary teeth and a higher number of filled primary teeth compared to the count at baseline (p = 0.027 and p = 0.058, respectively). Conclusion: Our study showed no detrimental effect of SLIT on oral health during a period of 19 months of follow-up. Parents should be motivated to use dental health services to prevent new caries formation since our cohort had overall poor oral hygiene at the baseline.

Quality-of-life outcomes in patients who underwent subcutaneous immunotherapy and sublingual immunotherapy in a real-world clinical setting.

To compare changes in quality of life (QOL) that resulted from sublingual immunotherapy (SLIT) and subcutaneous immunotherapy (SCIT) in a real-world clinical setting. SLIT is established as a viable alternative to SCIT for the treatment of allergic rhinitis. Although comparative trials are increasingly available, few studies have examined QOL outcomes between these two treatments. One hundred and five participants who underwent immunotherapy for airborne allergies were enrolled in this prospective, single-center study. Forty participants completed the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) at initiation of therapy, after 6 months, and after 1 year of therapy. Only patients with complete time points were included in the ultimate analysis. Twenty-nine of these participants underwent SCIT and 11 underwent SLIT. The effects of age, sex, and asthma history were also examined. The participants in both groups demonstrated improvements in QOL regarding allergic rhinoconjunctivitis over the study period. However, the change in the RQLQ score from both baseline to 6 months and baseline to 1 year was only statistically significant in the SCIT group (p = 0.002, 6 months and 1 year). The participants in the SCIT group also demonstrated statistically significant improvement from baseline to 1 year in the specific domains of practical and emotional functioning, nasal symptoms, non-nasal/eye symptoms, and sleep. After 1 year, both SCIT and SLIT demonstrated a minimally important difference from baseline in the overall RQLQ score. Age <35 years in the SCIT group had a significant positive impact on QOL improvement (p = 0.038). Although improvements in QOL were noted in both groups, changes in overall scores and the majority of domains only achieved statistical significance in the SCIT group. A small study population and difficulties adhering to immunotherapy dosing schedules in the SLIT group may be contributing factors.

Sublingual immunotherapy in patients with latex allergy: systematic review and meta-analysis of randomized controlled trials

Latex allergy (LA) is a commonly observed entity for which sublingual immunotherapy (SLIT) has been shown to be effective in many small randomized clinical trials. The present study was conducted with an aim of systematically reviewing the existing literature on the efficacy and safety of SLIT in patients with LA and to apply the principles of meta-analysis. A search for randomized controlled trials with appropriate search strategy in PubMed and CENTRAL was conducted. Studies with documented clinical history of LA and SLIT administered in any dose, duration and regimen compared with placebo were included. Outcome measures were symptom scores, glove provocation test score, serum IgE levels, induration following latex skin prick test, medication scores and adverse effects. Random effects model was used when moderate to severe heterogeneity was observed and fixed effects model when there was mild heterogeneity. Forest plots for standardized mean difference (95% confidence interval) for all the continuous outcome measures were created. A total of 152 records were identified from the electronic databases and four studies were finally included in the meta-analysis. A statistically significant reduction for induration following glove provocation test (pooled results from two studies) was observed in the SLIT group with SMD of −0.9 [−1.71, −0.08]. No significant differences were observed in any other outcome measures between the interventions. We did not identify significant reduction in most of the outcome measures with SLIT in patients with LA except for glove provocation test score wherein only two studies were included. Large and more randomized controlled trials are required to ascertain and confirm the utility of SLIT in such patients.

Sublingual immunotherapy for allergic rhinitis: subjective versus objective tools to evaluate its success

Biomarkers that enable objective evaluation of the clinical effects of immunotherapy for allergic rhinitis have yet to be identified. This study included 40 patients who were enrolled in a large randomized, double-blind, placebo-controlled, multicenter study examining the efficacy of sublingual immunotherapy (SLIT) using Japanese cedar (JC) pollen extract during two consecutive pollen seasons from 2010 to 2012. Based on changes in total nasal symptom medication score, patients in the SLIT and placebo groups were subdivided into two subgroups: good responders and poor responders. The levels of JC pollen-specific IL-10+Foxp3+ cells and specific Th2 cytokine-producing cells were measured and the association with the efficacy of SLIT was analysed. The total nasal symptom medication score was significantly lower in the SLIT group compared with the placebo group. The number of JC pollen-specific Th2 cytokine-producing cells increased during the pollen season in the placebo group and in poor responders in the SLIT group; however, the increases were inhibited in the good responders in the SLIT group. The number of JC pollen-specific IL-10+Foxp3+ cells increased only in these good responders. Changes in levels of allergen-specific Th2 cytokine-producing cells and IL-10+Foxp3+ cells could be objective biomarkers for SLIT.

SUBLINGUAL IMMUNOTHERAPY IN THE TREATMENT OF ALLERGIC ASTHMA: A SYSTEMATIC REVIEW WITH META-ANALYSIS

Introduction: The guidelines for the management of allergic respiratory diseases oriented towards control from medical treatment combined with measures of environmental hygiene. Immunotherapy is one of several types of treatment, applied in combination with prophylactic drugs and environmental care. The aim of the study is to evaluate the efficacy of sublingual immunotherapy (SLIT) for house dust mites (HDM) in people with allergic asthma. Methods: The study is based on a systematic review with meta-analysis of randomized clinical trials, associating sublingual immunotherapy with the treatment of allergic patients with HDM. Results: The searches were applied in PubMed, ScienceDirect and Scielo databases. Initially, 98 articles were recovered, of which only nine were eligible. Of these, eight (88.9%) were conducted in Europe and only one (11.1%) in Asia. Comparing the outcomes expiratory volume in the first minute (FEV 1 ) and sensitivity to allergens (HDM) between SLIT and placebo groups before and after intervention, no differences were observed between the groups. Conclusions: SLIT is not evidenced significantly by meta-analysis for the treatment of allergic asthma. Keywords: Mites; asthma; rhinitis; respiratory disease

スギ花粉症舌下免疫療法の治療2年目における症状改善の増強効果

Sublingual immunotherapy (SLIT) is thought to have enhanced efficacy in the second year of treatment. We studied treatment efficacy in both the first and the second years of treatment (2015 and 2016, respectively) in patients who began SLIT in 2014. Methods: We compared 132 patients who underwent SLIT (age, 41.8 ± 17.5 years; male-to-female ratio, 75: 57) and a control group of 56 patients who underwent primary pharmacotherapy (age, 44.9 ± 13.5 years; male-to-female ratio, 25: 31). The study was performed during the peak pollen seasons of 2015 and 2016. Pollen dispersal was similar in 2015 and 2016 (2,509 grains/cm2 and 3,505 grains/cm2, respectively). The clinical efficacy of SLIT was evaluated by assessing nasal and eye symptoms and total symptoms with symptom scores and combined symptom-medication scores, visual analog scale scores, and quality of life (QOL) scores according to the Japanese rhino-conjunctivitis QOL questionnaire (JRQLQ No. 1). QOL was also evaluated with JRQLQ No. 1. The first endpoint was enhanced efficacy of SLIT in the second year compared with that in the first year. Results: With respect to nasal and eye symptoms, the assessments in the primary pharmacotherapy group were unchanged in the second year; however, most of these assessments in the SLIT group demonstrated significantly enhanced efficacy of SLIT in the second year. In QOL of SLIT, only 2 of 17 showed significantly enhanced efficacy of SLIT in the second year. Conclusion: SLIT shows enhanced efficacy in the second year.

Sublingual immunotherapy for allergic rhinitis: subjective versus objective tools to evaluate its success.

Biomarkers that enable objective evaluation of the clinical effects of immunotherapy for allergic rhinitis have yet to be identified. This study included 40 patients who were enrolled in a large randomized, double-blind, placebo-controlled, multicenter study examining the efficacy of sublingual immunotherapy (SLIT) using Japanese cedar (JC) pollen extract during two consecutive pollen seasons from 2010 to 2012. Based on changes in total nasal symptom medication score, patients in the SLIT and placebo groups were subdivided into two subgroups: good responders and poor responders. The levels of JC pollen-specific IL-10+Foxp3+ cells and specific Th2 cytokine-producing cells were measured and the association with the efficacy of SLIT was analysed. The total nasal symptom medication score was significantly lower in the SLIT group compared with the placebo group. The number of JC pollen-specific Th2 cytokine-producing cells increased during the pollen season in the placebo group and in poor responders in the SLIT group; however, the increases were inhibited in the good responders in the SLIT group. The number of JC pollen-specific IL-10+Foxp3+ cells increased only in these good responders. Changes in levels of allergen-specific Th2 cytokine-producing cells and IL-10+Foxp3+ cells could be objective biomarkers for SLIT.

ASCIA‐P46: REVIEW OF IMMUNOTHERAPY PATIENTS IN A PRIVATE CLINIC

Specific Immunotherapy is a treatment offered to patients with severe allergic rhinoconjunctivitis or with insect venom hypersensitivity. We collated patients’ information from our computerised database over January 2012 to June 2016. Particular interests included patient demographic, allergen prescribed, method of delivery, compliance and completion rate of immunotherapy. A total of 311 patients were prescribed immunotherapy. 276 patients underwent subcutaneous immunotherapy (SCIT) and 44 patients received sublingual immunotherapy (SLIT). Approximately 50% of patients were administered SCIT comprising of a single injection with predominantly a single allergen. The commonest therapies instigated for single allergen were for dust mite 57% and bee venom 9%. The majority of patients (81%) who received 2 injections were for dust mite and grass pollen. As part of their grass pollen immunotherapy, up to 90% of patients also had subtropical grass pollen in their kit. At the conclusion of the study, data was again collated with regards to looking at patient completion rate. This finalisation of data interestingly coincided with the delay and disruption of immunotherapy supply in Australia. The data from the SCIT arm showed 15% of patients completed the course within the recommended time period, 28% ceased immunotherapy with no reasons given and 29% ceased due to delay in product availability. In the SLIT group 7% completed their course, 11% ceased with no reasons cited and 6% ceased due to delay in product availability. This completion rate of specific immunotherapy is compared to current available literature.

Effect of Japanese cedar–specific sublingual immunotherapy on allergen-specific TH2 cell counts in blood

BackgroundThe contribution of antigen-specific TH cells in peripheral blood to immunologic mechanisms underlying sublingual immunotherapy (SLIT) remains unclear, partly because of the lack of a standardized method for the analysis of this rare lymphocyte subset. ObjectiveTo clarify the role of antigen-specific TH cells during SLIT using a sensitive method analyzing activation marker CD154-positive TH cells with multicolor flow cytometry. MethodsWe assessed antigen-specific TH cells using multicolor flow cytometry based on the expression of the activation marker CD154 and intracellular cytokines in patients with Japanese cedar pollinosis receiving SLIT at baseline and during the first pollen season after the initiation of SLIT. ResultsA total of 18 patients between 12 and 44 years of age were enrolled in the present study. Of these, 8 patients received SLIT (SLIT group) and 10 patients received symptomatic treatment only (control group). Although seasonal pollen exposure significantly increased the number of Japanese cedar–specific interleukin 5– and interleukin 4–producing TH cells in the control group (P < .01 for both), SLIT ameliorated this increase in the SLIT group (P = .64 and P = .84, respectively). ConclusionThe present study indicates that allergen-specific TH2 cells in peripheral blood are involved in mechanisms underlying SLIT. The analysis of antigen-specific TH cells using multicolor flow cytometry based on the expression of the activation marker CD154 represents a sensitive and relatively simple, standardized method for monitoring peripheral antigen-specific TH cells during allergen-specific immunotherapy.

Oral mucosal immunotherapy for allergic rhinitis: A pilot study.

Background:The sublingual mucosa has been used for many years to apply allergenic extracts for the purpose of specific immunotherapy (IT). Although sublingual IT (SLIT) is both safe and efficacious, the density of antigen-presenting cells is higher in other regions of the oral cavity and vestibule, which make them a potentially desirable target for IT.Objective:To present the concept of oral mucosal IT (OMIT) and to provide pilot data for this extended application of SLIT.Methods:An open-label, 12-month, prospective study was undertaken as a preliminary step before a full-scale clinical investigation. Twenty-four individuals with allergic rhinitis received IT by applying allergenic extracts daily to either the oral vestibule plus oral cavity mucosa by using a glycerin-based toothpaste or to the sublingual mucosa by using 50% glycerin liquid drops. Adverse events, adherence rates, total combined scores, rhinoconjunctivitis quality-of-life questionnaire scores, changes in skin reactivity, and changes in serum antibody levels were measured for each participant.Results:No severe adverse events occurred in either group. The adherence rate was 80% for the OMIT group and 62% for the SLIT group (p = 0.61). Decreased total combined scores were demonstrated for both the OMIT group (15.6%) and the SLIT group (22.3%), although this decrease did not reach statistical significance in either group. Both groups achieved a meaningful clinical improvement of at least 0.5 points on rhinoconjunctivitis quality-of-life questionnaire. A statistically significant rise in specific immunoglobulin G4 (IgG4) was seen in both groups over the first 6 months of treatment.Conclusion:OMIT and SLIT demonstrated similar safety profiles and adherence rates. Measurements of clinical efficacy improved for both groups, but only changes in IgG4 achieved statistical significance. These pilot data provide enough evidence to proceed with a full-scale investigation to explore the role of OMIT in the long-term management of allergic rhinitis.

The effects of house dust mite sublingual immunotherapy in patients with allergic rhinitis according to duration.

The safety and efficacy of sublingual immunotherapy (SLIT) have been demonstrated in the recent 2 decades. However, the data is still mixed regarding the efficacy of house dust mite (HDM) SLIT. The objective of this work was to evaluate the different clinical efficacy SLIT in patients with allergic rhinitis (AR) according to different durations of treatment. A total of 500 subjects with HDM-induced AR were randomized to receive SLIT with Dermatophagoides farinae (Der.f) drops or pharmacotherapy with oral antihistamines. Patients in the SLIT group were further divided into SLIT1, SLIT2, and SLIT3 subgroups. After SLIT completion, a yearly follow-up visit was given to patients in the SLIT1 and SLIT2 subgroups. The total nasal symptom score (TNSS), the proportion of medication withdrawal, the visual analogue scale (VAS) score, and Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) scores were assessed at each monthly visit. Comparing with the baseline value, TNSS, VAS, and RQLQ were significantly improved in 3 SLIT subgroups after treatment (p < 0.05). In addition, patients in SLIT3 subgroup achieved the highest proportion of medication withdrawal compared to the SLIT1 and SLIT2 subgroups (p < 0.05). After 1-year follow-up, no significant differences were observed in TNSS, VAS scores, and the proportion of medication withdrawal of SLIT1 and SLIT2 subgroups (p > 0.05) with respect to the completion value. No severe systemic adverse events (AEs) were reported. The randomized study suggested that 3-year courses of SLIT in patients with AR was more efficacious than 1-year or 2-year courses. Furthermore, patients achieved 1-year long-term clinical benefits from HDM SLIT.

Increased Expression of miR-146a in Children With Allergic Rhinitis After Allergen-Specific Immunotherapy.

PurposeMicroRNAs (miRs) were recently recognized to be important for immune cell differentiation and immune regulation. However, whether miRs were involved in allergen-specific immunotherapy (SIT) remains largely unknown. This study sought to examine changes in miR-146a and T regulatory cells in children with persistent allergic rhinitis (AR) after 3 months of subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT).MethodsTwenty-four HDM-sensitized children with persistent AR were enrolled and treated with SCIT (n=13) or SLIT (n=11) for 3 months. Relative miR-146a and Foxp3 mRNA expression, the TRAF6 protein level, and the ratio of post-treatment to baseline IL-10+CD4+ T cells between the SCIT and SLIT groups were examined in the peripheral blood mononuclear cells (PBMCs) of AR patients using quantitative reverse transcription polymerase chain reaction (qRT-PCR), flow cytometry, and Western blot analysis, respectively. Serum levels of IL-5 and IL-10 were determined using ELISA.ResultsAfter 3 months of SIT, both the TNSS and INSS scores were significantly decreased compared to the baseline value (P<0.01). The relative expression of miR-146a and Foxp3 mRNA was significantly increased after both SCIT and SLIT (P<0.01). The ratio of post-treatment to baseline IL-10+CD4+ T cells and the serum IL-10 level were significantly increased in both the SCIT and SLIT groups (P<0.01), whereas the TRAF6 protein level and serum IL-5 level were significantly decreased (P<0.01). No significant differences in these biomarkers were observed between the SCIT and SLIT groups.ConclusionsOur findings suggest that miR-146a and its related biomarkers may be comparably modulated after both SCIT and SLIT, highlighting miR-146a as a potential therapeutic target for the improved management of AR.

Efficacy of Grass Pollen Allergen Sublingual Immunotherapy Tablets for Seasonal Allergic Rhinoconjunctivitis: A Systematic Review and Meta-analysis.

Randomized clinical trials (RCTs) and meta-analyses of sublingual immunotherapy (SLIT) for the treatment of seasonal allergic rhinoconjunctivitis (SARC) have shown a modest clinical benefit compared with placebo. Furthermore, indirect comparison by meta-analyses showed that subcutaneous immunotherapy is more effective than SLIT. Despite these data, SLIT has become the most prescribed treatment of SARC in Europe in recent years, and it was approved by the US Food and Drug Administration for the treatment of SARC to grass pollen in the United States on April 1, 2014. To assess the efficacy and safety of the grass pollen sublingual tablets licensed as drugs in the treatment of patients with SARC to grass pollen. Computerized bibliographic searches of MEDLINE, EMBASE, the Cochrane Library, and ClinicalTrials.gov (from inception to April 30, 2014) were supplemented with a manual search of reference lists. Randomized clinical trials were included if they compared the grass pollen SLIT tablets approved by regulatory authorities in the European Union and the United States for SARC with placebo. Data on populations, interventions, and outcomes were extracted from each RCT according to the intent-to-treat method by 2 independent observers and were combined using the method by DerSimonian and Laird. The primary end point was the difference in the symptom score and medication score between SLIT and placebo. We pooled data using random-effects meta-analysis, with standardized mean differences (SMDs) and 95% CIs reported. Data were available in 13 RCTs for the symptom score (4659 patients) and in 12 RCTs for the medication score (4558 patients). We found a small treatment benefit in the symptom score (SMD, -0.28; 95% CI, -0.37 to -0.19; P < .001) and in the medication score (SMD, -0.24; 95% CI, -0.31 to -0.17; P < .001). Adverse events were reported in 1384 of 2259 patients (61.3%) receiving SLIT and in 477 of 2279 patients (20.9%) receiving placebo. Seven patients in the SLIT group reported treatment-related adverse events requiring epinephrine. Findings show a small benefit of the grass pollen sublingual tablets in reducing symptoms and in decreasing the use of symptomatic medication (antihistamines and corticosteroids) in patients with SARC. Considering the low magnitude of the benefit, the convenience and easy administration do not seem to be sufficient reasons for the choice of SLIT.

Sublingual Immunotherapy for Asthmatic Children Sensitized to House Dust Mite: A Meta-Analysis.

The house dust mite is one of the most common allergens worldwide. There is good evidence that house dust mite subcutaneous immunotherapy is efficacious and has long-term benefit in children. However, the evidence of the benefit of house dust mite sublingual immunotherapy (SLIT) is less convincing. The purpose of this meta-analysis was to evaluate that efficacy and safety of dust mite SLIT in children with asthma.Medical Literature Analysis and Retrieval System Online, ISI Web of Knowledge, and Cochrane Central Register of Controlled Trials databases until February 2014 were searched. The primary outcome was mean change in asthma symptom score. Secondary outcomes included mean change in serum immunoglobulin G4 (sIgG4), specific Dermatophagoides pteronyssinus, immunoglobulin E (IgE) levels, and medication score. Safety was also assessed.We found that SLIT significantly decreased asthma symptom score (P = 0.007) and increased sIgG4 levels (P = 0.011) greater than control in children (<18 years of age) with asthma. There was no difference between SLIT and control groups in specific D pteronyssinus IgE levels (P = 0.076) and medication score (P = 0.408). The safety profile was similar between groups.Our study indicates that dust mite SLIT therapy was effective in reducing asthma symptoms and in increasing sIgG4 but did not significantly reduce medication scores or specific D pteronyssinus IgE levels. Our findings are not enough to support the use of dust mite SLIT in children with asthma.

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.

Clinical and cytokine responses to house dust mite sublingual immunotherapy

BackgroundCytokine responses accompanying sublingual immunotherapy (SLIT) responder phenotypes have not previously been reported. ObjectiveTo investigate clinical and cytokine responses of house dust mite (HDM) sensitive patients with allergic rhinitis receiving HDM SLIT or placebo for 2 years. MethodsSixty adults were randomized to receive SLIT or placebo. Clinical symptoms were measured using the Total 5 Symptom Score (TSS5) and Juniper Rhinitis Quality of Life Questionnaire. HDM specific IgE, IgG, skin prick tests, and HDM-stimulated release of interleukin (IL) 5 and interferon γ (IFN-γ) in peripheral blood mononuclear cells was studied at 0, 6, 12, and 24 months and IL-13, IL-4, and IL-10 at 0 and 24 months. ResultsA total of 32 of 39 SLIT and 16 of 21 placebo patients completed the study. There was significant clinical improvement in both the SLIT and placebo groups. Median T5SS decreased from 14.75 to 5.25 in the SLIT group (P < .001) and 12.7 to 6.0 in the placebo group (P = .003). The median quality-of-life score also decreased in the SLIT group (P < .001) and the placebo group (P < .001). A subgroup analysis of patients found a 60% or greater improvement (on the T5SS and the Juniper Rhinitis Quality of Life Questionnaire) in the good responders group and a 30% to 59% improvement or no improvement in the intermediate responders group. This subgroup analysis also found more good responders in the SLIT group (47%) compared with the placebo group (25%; P = .07). Significant decreases in the IL-5/IFN-γ (P < .001), IL-13/IFN-γ (P < .001), and IL-4/IFN-γ (P = .03) ratios were found in the combined good clinical improvement group at 24 months. ConclusionA good clinical response (≥60% improvement in both TSS5 and quality of life) is associated with significant decreases in IL-5, IL-13, and IL-4 relative to IFN-γ during 2 years of SLIT therapy for HDMs.

Changes of micro-RNAs in asymptomatic subjects sensitized to Japanese cedar pollen after prophylactic sublingual immunotherapy.

Japanese cedar pollinosis is the predominant seasonal allergic rhinitis in Japan, and it has increased in prevalence during the past 10 years. Sublingual immunotherapy (SLIT) is considered a safe and effective treatment for pollinosis. Micro-RNAs (miRNAs) are a class of short single-stranded RNA molecules that posttranscriptionally silence gene expression and may mediate allergic immune responses. The aim of this study was to investigate the miRNA alteration in asymptomatic subjects sensitized to Japanese cedar pollen under prophylactic SLIT under part of a randomized, double-blind, placebo-controlled, multiple-center trial. Analysis was undertaken in 15 asymptomatic subjects sensitized to Japanese cedar pollen–specific IgE (ImmunoCAP class ≥2) who participated in 2013. The SLIT group (n = 6) received standardized Japanese cedar pollen extract and the placebo group (n = 9) received an inactive placebo for 5 months covering the cedar pollen season. Changes in serum miRNAs were measured by real-time quantitative polymerase chain reaction to determine whether SLIT had effects on profiles of circulating miRNA. Seven subjects in the placebo group developed pollinosis symptoms, whereas no subjects in the SLIT group did (p = 0.007). Serum hsa-miR-223 was significantly up-regulated in postseason compared with preseason samples. The hsa-let-7b was significantly more down-regulated in postseason than in preseason samples from the placebo group; however, no significant differences were observed in those from the SLIT group. A significant decrease in circulating let-7b was also observed in the subjects who developed symptoms. Prophylactic SLIT was effective in preventing the development of pollinosis. Alterations in miRNA expression occurred in asymptomatic, sensitized subjects during cedar pollen season.

Comparison of short-term effects between subcutaneous and sublingual immunotherapies in children with house dust mite-sensitized allergic rhinitis and asthma

Purpose: There have been several studies on comparisons of efficacy between subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) in children with house dust mite (HDM)-sensitized allergic rhinitis (AR), without consistent results. This study was conducted to compare short-term effects between SCIT and SLIT in Korean children with HDM-sensitized AR. Methods: Fifty-three children (mean age, 11.15±2.82 years) with HDM-sensitized AR and with/without asthma (SCIT group, n=33; SLIT group, n=20) were enrolled. Clinical symptom scores and skin prick test results were assessed before, and after 3, 6, and 12 months of immunotherapy. Blood tests, including eosinophils, total serum IgE, and HDM-specific IgE, and adenosine 5’-monophosphate, and methacholine bronchial challenge tests were performed before and after 12 months of immunotherapy. Results: In the SCIT group, the symptom scores improved after 3 months compared to those before immunotherapy, whereas they improved after 6 months in the SLIT group. Significant decreases in skin reactivity to HDM were observed after 3 months only in the SCIT group. Decreases in total eosinophil counts and improvements in methacholine bronchial provocation tests were observed after 12 months of immunotherapy only in the SCIT group. No difference in severe adverse reactions was noted in either group. Conclusion: The results of this study suggest that SCIT may have more rapid effects on clinical symptoms and skin reactivity in children with AR, compared to SLIT.(Allergy Asthma Respir Dis 2015;3:180-186)