House Dust Mite SLIT-tablet Research Articles

Consistent efficacy and safety of sublingual immunotherapy tablets across allergens and geographic regions.

Background: The clinical development program of the SQ grass, ragweed, tree, and house dust mite (HDM) sublingual immunotherapy (SLIT)-tablets for allergic rhinitis/conjunctivitis (AR/C) included clinical trials conducted in North America, Europe, and Japan. Objective: Data from these trials were analyzed to assess efficacy, immunologic mechanisms, and safety outcomes across allergens and geographic regions. Methods: Thirteen phase III, double-blind, placebo controlled trials in the subjects with AR/C were conducted in North America, Europe (including Russia), and Japan (N = 7763 analyzed). Trials were generally similar with respect to medical practice, target population, eligibility criteria, and efficacy and safety monitoring. Data were analyzed for the approved doses in North America and Europe. Four statistical models were used to enhance comparison of the efficacy end points among the trials. Results: The SLIT-tablets demonstrated consistent efficacy across allergens and regions, regardless of the statistical analysis used. Relative improvement in the primary efficacy end point compared with placebo by using the predefined protocol analysis ranged from 17.9% to 32.8%, 17.5% to 19.3%, 20.6% to 38.3%, and 39.6% with the grass, HDM, ragweed, and tree SLIT-tablets, respectively. The kinetics of specific immunoglobulin E (IgE) and IgG4 responses were similar among the allergens and regions. Local application-site reactions were the most common adverse events for all allergens and in all regions. Most treatment-related adverse events for all allergens and in all regions were mild in severity. The rate of systemic allergic reactions was similar across regions (0%-0.54%). Conclusion: Confirmatory phase III trials for SLIT-tablets in the treatment of AR/C showed consistent efficacy, immunologic, and safety outcomes across allergens and geographic regions.

Real-world assessment of anaphylaxis and eosinophilic esophagitis with 12 SQ house dust mite SLIT-tablet sublingual immunotherapy

Sublingual immunotherapy (SLIT) with 12 SQ house dust mile SLIT-tablet (HDM SLIT-tablet) for dust mite-induced perennial allergic rhinitis is reported as effective and safe. Although serious allergic reactions (SARs) and eosinophilic esophagitis (EoE) have infrequently occurred under trial conditions, the safety of HDM SLIT-tablet challenge under real-world conditions is unknown. Our aim was to estimate the incidence of SARs and EoE due to HDM SLIT-tablet challenge. Through use of administrative data from Kaiser Permanente Southern California, this prospective observational study identified patients newly administered HDM SLIT-tablet with follow-up until SLIT discontinuation or end of study. Suspected cases of SARs and EoE were detected by using International Classification of Diseases, 10th Revision, diagnosis and Current Procedural Terminology procedure codes and medication dispensing records. A3-member clinical review committee of allergists adjudicated suspected reactions. The incidence rate of confirmed SARs and EoE per 1000 person years of exposure were determined. A total of 521 patients (93.9% adult and 6.1% pediatric) were exposed to HDM SLIT-tablet challenge from January 2018 through May 2023, for 440.4 person years of exposure. The patients' average age (SD) was 39.3 (14.1) years, 58.7% were female, 44.3% were non-Hispanic White, 40.3% had asthma, and 15.0% had gastroesophageal reflux disease. ASAR occurred in 1 adult patient, and during initial HDM SLIT-tablet challenge, SARs occurred in 2 pediatric adolescents, for an overall incidence of 6.8 SARs per 1000 patient years (95% CI= 2.2-21.1). EoE occurred in 1 adult patient, for an overall incidence of 2.3 cases of EoE per 1000 patient years (95% CI= 0.3-16.1). This real-world study demonstrated that SARs and EoE were infrequent events with HDM SLIT-tablet use, supporting the safety of HDM SLIT-tablets and need for physician supervision with initial challenge.

Efficacy of 300 IR house dust mite immunotherapy as a function of disease activity: Tertile analysis in clinical trials.

The symptoms of house dust mite (HDM)-induced allergic rhinitis (AR) vary with changes in exposure related to the weather or the domestic environment. In allergen immunotherapy (AIT) studies, a certain level of AR disease activity is necessary to demonstrate treatment efficacy; the latter can be underestimated if a substantial proportion of the patient population is weakly symptomatic. To better estimate the real treatment effect of a HDM sublingual AIT (SLIT) tablet, we analysed the results of natural field studies in detail by applying a tertile approach. We used data from three randomised, controlled trials (RCT) in a total of 2585 patients with AR treated with the 300 index of reactivity (IR) HDM SLIT-tablet or placebo. The study centres were grouped into tertiles according to the level of combined symptom and medication scores in patients in the placebo group. In each tertile, the difference between SLIT and placebo was assessed through an analysis of covariance. In the three RCTs, combined scores were found to be similar in the SLIT and placebo groups in the low tertiles. The treatment effect of the 300 IR HDM tablet increased in the medium and high tertiles, with notably significant differences versus placebo in the highest tertile and greater (ranging from -21% to -39%) than in the entire study population (-13% to -20%). The positive relationship between treatment efficacy and the combined score in each tertile was independent of the RCT and the score used. Application of the tertile approach to AIT studies in a field in which many variables interact strongly might provide more accurate and meaningful measurements of efficacy and benefit for patients, better reflecting their real-life condition.

House dust mite sublingual allergen immunotherapy tablet is safe and well-tolerated in Dutch clinical practice.

Half (49%) of clinically diagnosed allergic rhinitis (AR) patients are sensitized to house dust mite (HDM). If allergen avoidance and symptomatic medication fail, allergen immunotherapy may be indicated. We investigated safety and tolerability of HDM-sublingual immunotherapy by HDM-SLIT tablets in Dutch daily clinical practice. Daily intake of 12 SQ-HDM SLIT-tablet was investigated in a prospective, multicenter, observational study (EUPAS43753). It comprised 4 consultations in 1 year. Data on safety, tolerability, treatment satisfaction, symptomatic medication, compliance, and clinical effectiveness (Control of Allergic Rhinitis and Asthma Test; CARAT) were collected. Descriptive and longitudinal regression data analysis were performed. Adult patients (n = 415), mean (SD) age 36.6 (12.2) years, 61.4% female and 36% asthmatic were included. The preponderance (65.1%) experienced adverse events (AEs). These, mostly mild (67%), AEs comprised: oral allergic reactions (58.6%), respiratory (12.4%) and gastrointestinal symptoms (9.4%). Sixty (14.5%) patients stopped due to AEs and 76 (18.3%) for non-AE reasons. CARAT scores improved clinically significant by 6 points and symptomatic medication use decreased from 96.1% to 77.4%. Most patients (74.5%) tolerated the treatment and were compliant (>86.5%). The majority of patients (62.4%) and investigators (69.4%) were satisfied with treatment. HDM SLIT-tablet is a safe and well-tolerated AR treatment. AEs occur often but are mostly mild and decreasing during the first year. CARAT scores improved and symptomatic medication use decreased suggesting better control of AR with treatment. Compliance, tolerability, and treatment satisfaction are good. However, patient follow-up and compliance remain important points of attention when initiating treatment.

Genetic and T2 biomarkers linked to the efficacy of HDM sublingual immunotherapy in asthma

BackgroundHypersensitivity to house dust mite (HDM) allergens is a common cause of allergic asthma symptoms and can be effectively treated with allergy immunotherapy (AIT).ObjectiveTo investigate whether genetic and type 2...

House dust mite sublingual immunotherapy tablet safety in adolescents with allergic rhinoconjunctivitis: Worldwide clinical trial results

BackgroundThe house dust mite (HDM) sublingual immunotherapy (SLIT)-tablet is a treatment option for allergic rhinitis with/without conjunctivitis (AR/C) approved in adults worldwide and in adolescents in some countries. ObjectiveTo supplement existing adolescent HDM SLIT-tablet safety data by conducting the MT-18 trial in adolescents. MethodsMT-18 (EudraCT:2020-000446-34) was a phase 3, open-label, single-arm, 28-day safety trial of daily HDM SLIT-tablet (12 SQ-HDM dose) in European adolescents (12-17 years) with HDM AR/C, with or without asthma. The primary end point was at least 1 treatment-emergent adverse event (TEAE). MT-18 results were compared with 12 SQ-HDM adolescent subpopulation data from previously described 1-year phase 3 trials conducted in North America (P001; clinicaltrials.gov:NCT01700192) or Japan (TO-203-3-2; JapicCTI:121848). ResultsNo treatment-related anaphylaxis, epinephrine administrations, severe local swellings, severe mouth or throat edema, or eosinophilic esophagitis occurred in the trials. For MT-18 (N = 253), P001 (N adolescents = 189), and TO-203-3-2 (N adolescents = 206), the percentage of adolescents treated with 12 SQ-HDM reporting any TEAE was 88%, 95%, and 93%, respectively, and the percentage reporting any treatment-related AE (TRAE) was 86%, 93%, and 66%, respectively. The most common TRAEs were local application site reactions. Most TRAEs were mild in intensity and were typically experienced the first 1 to 2 days of treatment. There were no asthma-related TEAEs with the HDM SLIT-tablet. The safety profile appears similar between adolescents with or without asthma at baseline. ConclusionThe HDM SLIT-tablet was well tolerated in European, North American, and Japanese adolescents with HDM AR/C, indicating safety of the HDM SLIT-tablet is insensitive to age or geographic region. Trial registrationClinicalTrials.gov Identifier: (P001: NCT01700192); EudraCT: (MT-18; 2020-000446-34); JapicCTI: (TO-203-3-2; 121848)

Efficacy and safety of sublingual allergen immunotherapy.

Sublingual immunotherapy (SLIT)-tablets represent a new allergen immunotherapy option for clinicians. In North America, there are five SLIT-tablets approved for the treatment of allergic rhinoconjunctivitis (ARC). No SLIT-drops products are currently approved in the United States or Canada. This work reviewed the efficacy of the timothy grass SLIT-tablet, five-grass SLIT-tablet, ragweed SLIT-tablet, house-dust mite SLIT-tablet, and tree SLIT-tablet in patients with ARC. All the SLIT-tablets showed consistent clinical efficacy for the treatment of ARC in large, double-blind, placebo-controlled trials, including for both patients who were monosensitized and those who were polysensitized. Treatment with house-dust mite SLIT-tablet has shown efficacy in patients who are pollen sensitized during their respective pollen seasons. In contrast to SLIT-tablets, efficacy studies of SLIT-drops show high heterogeneity of treatment effect. Although data are scarce, data that compared the efficacy of SLIT-tablets versus ARC pharmacotherapy generally indicated that SLIT-tablets had a greater benefit than pharmacotherapy when compared with placebo, particularly for perennial ARC. When compared with subcutaneous immunotherapy, analysis of these data indicated that SLIT-tablets had a benefit over subcutaneous immunotherapy in regard to safety but somewhat less benefit in regard to efficacy. The safety of SLIT-tablets has been well documented, and a U.S. Food and Drug Administration class label with safety considerations is present in the prescribing information for all SLIT-tablets. No new safety signals have been observed after reinitiating SLIT-tablets after a short treatment interruption.

The SQ HDM SLIT-Tablet is safe and well tolerated in patients with House Dust Mite allergic rhinitis with or without asthma: A "real-life" French study.

BackgroundThe SQ House Dust Mite (HDM) SubLingual ImmunoTherapy (SLIT)‐Tablet (Acarizax) is the only allergen immunotherapy authorized by European regulatory authorities to treat HDM‐induced allergic asthma (AA) that is not well‐controlled by inhaled corticosteroids and associated with mild‐to‐severe HDM allergic rhinitis (AR). The aim of this study was to add evidence on the safety of the SQ HDM SLIT‐Tablet in patients with AR, alone or with AA, under real‐life conditions.MethodsThis was a French “real‐life”, multicenter, non‐comparative, longitudinal, prospective study. It included patients initiating the SQ HDM SLIT‐Tablet for either persistent moderate‐to‐severe HDM AR or AA not well‐controlled by inhaled corticosteroids and associated with mild‐to‐severe HDM AR. Adverse Events (AEs) were collected at the first intake and throughout the study. Logistic regression was used to compare safety according to asthma control before treatment initiation.ResultsBetween May 09, 2018 and May 29, 2019, 1526 patients were enrolled at 185 sites and 1483 were included in the safety population (SAF). Of them, 33.6% had suspected clinical manifestations of AA. Asthma was uncontrolled for 18.2% of the patients, partially controlled for 27.9% and well‐controlled for 53.8%. Overall, 31.9% of the SAF patients experienced at least one AE. The percentage of patients with AEs was 29.9% among patients with AR alone and 35.9% among those with AA (p = 0.0193). No significant difference was observed in the rate of AE or SAE depending on asthma control at inclusion (2.2% of SAEs reported for patients with uncontrolled asthma, 1.4% for partly controlled and 1.1% for well‐controlled).ConclusionsThe overall results indicate a good SQ HDM SLIT‐Tablet safety profile consistent with that reported in previous studies, regardless of asthma control.

Post-Marketing Survey Evaluating the Safety and Efficacy of the SQ House Dust Mite (HDM) Sublingual Immunotherapy-Tablet in Japanese Patients with HDM-Induced Allergic Rhinitis (Stratified analysis by 18 years, 2016-2020)

The SQ house dust mite (HDM) sublingual immunotherapy (SLIT) tablet (10,000 JAU, Torii, Japan/6 SQ-HDM, ALK, Denmark) has been available for HDM allergic rhinitis (AR) in Japan since 2015. This post-marketing surveillance investigates the safety and efficacy of 3 years of treatment with the SQ HDM SLIT-tablet.

A Real-Life One-Year Non-Interventional Study Assessing Safety, Tolerability, and Treatment Outcome of the SQ HDM SLIT-Tablet (Acarizax®) in House Dust Mite Allergic Rhinitis With or Without Asthma.

IntroductionThe aim of this study was to investigate the safety profile, tolerability, and outcome of the SQ® house dust mite (HDM) sublingual immunotherapy (SLIT)-tablet after 1 year of treatment in clinical practice among adults with HDM-related allergic rhinitis (AR) ± allergic asthma (AA).MethodsIn a non-interventional multicenter, observational study, patients were followed at 3 visits for 1 year. Adverse events (AE) were recorded at all visits. Patients graded their allergic symptoms as none, mild, moderate, or severe, and recorded AR and AA medication use. Asthma symptom control was assessed according to the Global Initiative for Asthma (GINA).ResultsOne hundred and ninety-eight patients were included; 115 (58%) had AR without asthma and 83 (42%) had both AR and AA. One hundred and sixty-six (84%) patients completed the study. Eighty percent of patients experienced an AE: 151 (75%) AEs were mild, 42 (21%) moderate, and 4 (2%) severe. Three patients (1.5%) reported four events that were considered serious (SAEs). One SAE was considered possibly treatment-related. No anaphylactic reactions occurred. The proportion of patients experiencing allergy symptom reductions by at least one step were 75% (nasal), 62% (eye), 16% (skin), and 13% (other symptoms); 75% of patients with AA experienced a decrease of at least one step in bronchial symptoms. AR medication and inhaled corticosteroids were statistically significant reduced.ConclusionThe SQ HDM SLIT-tablet was safe and well tolerated; the type, frequency, and severity of AEs resembled what RCTs have previously demonstrated. As explorative endpoints, statistically significant reductions in AR and AA symptoms and medication use were seen along with improved asthma control after 1 year of treatment, implying that clinically meaningful changes were seen after 1 year of treatment with the SQ HDM SLIT-tablet.Supplementary InformationThe online version contains supplementary material available at 10.1007/s41030-021-00150-z.

House dust mite SLIT-tablet is well tolerated in pediatric patients with controlled asthma.

: Despite the reported clinical effectiveness of house dust mite (HDM) sublingual immunotherapy (SLIT) in pediatric patients, the risk of treatment remains unclear in pediatric patients with allergic asthma. To show a risk of adverse drug reactions (ADRs) in pediatric patient with allergic asthma during the initiation period of HDM SLIT. We retrospectively analyzed the clinical data of pediatric patients aged ≤ 15 years who initiated allergen immunotherapy (AIT) with the SQ HDM SLIT-tablet for allergic rhinitis between February 2017 and September 2019. Asthma severity at baseline and ADRs during the first 4 weeks of the treatment were determined for each subject. In our study population (n = 217; median age, 8.4 years), 99 patients (45.6%) were classified as having asthma. One hundred and one patients (46.5%) in the whole cohort experienced ADRs during the first 4 weeks of therapy, but a major gap in the frequency of ADRs was not observed between an asthma group and a non-asthma group. The SQ HDM SLIT-tablet was well tolerated in pediatric patients with controlled HDM-driven allergic asthma. HDM-SLIT is an option to treat their allergic rhinitis without excessive concern for its ADRs.

The Effective Allergenic Reactivity of House Dust Mite Sublingual Immunotherapy Tablets Is Determined by Tablet Formulation.

House dust mite (HDM) sublingual immunotherapy (SLIT) in the form of SLIT-tablets is now an established treatment option for HDM allergy and HDM-induced allergic asthma. In SLIT-tablet immunotherapy allergen extracts are formulated as dry tablets and administered under the tongue where it must be solubilized in saliva in order to be able to interact with the immune system of the sublingual mucosa. Solubilization of the extract must occur within a short time span of about one minute after administration, determined by the sublingual holding time recommended by the manufacturer. Currently, two types of HDM SLIT-tablets are available. Both tablet types contain natural HDM extracts from two common HDM species as the active ingredient, but differ with regard to formulation as one tablet type is based on a freeze-dried tablet formulation while the other is based on a compressed formulation. HDM extracts contain a number of major and minor allergens, which in combination provide the allergenic activity that drives the immunological response and in turn the clinical efficacy of the tablets. Here, a biologically relevant human immunoglobulin E (IgE)-based assay is used to compare the ability of the two HDM SLIT-tablet types to deliver HDM allergenic reactivity from the dry tablet into soluble form. The experiments demonstrate that the freeze-dried formulation delivers HDM allergenic activity into solution faster and more efficiently than the compressed formulation.

Effect of House Dust Mite SLIT-tablet Treatment on Quality of Sleep in Allergic Rhinitis Patients

Effect of House Dust Mite SLIT-tablet Treatment on Quality of Sleep in Allergic Rhinitis Patients

Safety profile of the SQ house dust mite sublingual immunotherapy-tablet in Japanese adult patients with house dust mite-induced allergic asthma: a randomized, double-blind, placebo-controlled phase I study

Objective: The SQ house dust mite (HDM) sublingual immunotherapy (SLIT)-tablet has demonstrated effective treatment of HDM-induced allergic asthma in patients 18 years or older in European trials. This study investigated its safety and immunology profile in Japanese adult patients with mild-to-moderate HDM-induced allergic asthma. Methods: In this randomized, double-blind, placebo-controlled study, 48 Japanese patients were randomly assigned to a daily treatment of SQ HDM SLIT-tablet or placebo (3:1) for 14 d with or without an up-dosing regimen. Active groups comprised 5000, 10,000 or 20,000 Japanese Allergy Unit (JAU) for 14 d, and the up-dosing group comprised 5,000 JAU in day 1–3, 10,000 JAU in day 4–7 and 20,000 JAU in day 8–14. Results: No marked differences were observed in the incidence rate of adverse events (AEs) and their severity among active groups. The five most common investigational medicinal product (IMP)-related AEs were local events at the application site observed within 30 min after the intake of the SQ HDM SLIT-tablet. Although most events recovered within 1 h, mouth edema indicated a different profile of duration with more than 25% of the events lasting for more than 1 h. Conclusions: The SQ HDM SLIT-tablet of up to 20,000 JAU was well tolerated, and safety profile was acceptable for Japanese subjects with HDM-induced allergic asthma.

Cost-effectiveness of the SQ HDM SLIT-tablet for the treatment of allergic asthma in three Eastern European Countries.

Background.The SQ® house dust mite (HDM) sublingual immunotherapy (SLIT)-tablet (ACARIZAX®, ALK-Abelló A/S, Hørsholm, Denmark) is an allergy immunotherapy tablet for people with allergic respiratory disease. This analysis aims to assess the cost-effectiveness of the SQ HDM SLIT-tablet from the perspective of three Eastern European countries: Czech Republic, Poland and Slovakia. Methods.A cost-utility model per country was developed, which compared the SQ HDM SLIT-tablet as add-on to pharmacotherapy with pharmacotherapy alone in patients with HDM allergic asthma (AA) over a five year time horizon. The effectiveness of the two interventions was based on the results from a large-scale randomised controlled trial. In the models, annual costs and quality-adjusted life year (QALY) scores from the trial were extrapolated over a five year period, and the incremental cost-effectiveness ratios (ICERs) were estimated. One-way deterministic sensitivity and scenario analyses were undertaken. Results.The SQ HDM SLIT-tablet is cost-effective in all three markets over the five year time horizon (ICERs of less than € 10,000 per additional QALY). Treatment with the SQ HDM SLIT-tablet improves patient outcomes, with QALY gains of 0.35, versus pharmacotherapy only. In all three countries, the SQ HDM SLIT-tablet also incurs increased costs compared to pharma-cotherapy treatment only. The sensitivity analysis identified utility values from the clinical trial as the main driver of the model results. Conclusion.The SQ HDM SLIT-tablet is a cost-effective treatment option for people with HDM AA in three different health care settings in Eastern Europe.

UNCONTROLLED ALLERGY IS ASSOCIATED WITH SIGNIFICANT PRODUCTIVITY LOSS AMONG WORKING AMERICANS

Introduction Uncontrolled allergic rhinitis negatively impacts workplace productivity. House dust mite (HDM) is the most prevalent perennial allergy, but it can be effectively treated with allergy immunotherapy (AIT). Subcutaneous injection (SCIT) is the most common route of HDM AIT, however SCIT itself can adversely affect workplace productivity when the travel time required to receive the injections overlaps the workday. Methods This is an assessment, using an economic model, of the productivity impact of uncontrolled allergy in the US and an evaluation of the productivity impact of SCIT versus a new FDA-approved form of AIT, sublingual immunotherapy tablet (SLIT-tablet). The productivity impact is split into absenteeism and presenteeism. Results For the average employee with uncontrolled allergy the estimated annual productivity loss is $4,500, where presenteeism accounts for 81% of that total. In the pivotal North American placebo-controlled trial with HDM SLIT-tablet, statistical significant improvement was demonstrated by the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) in the activities domain (p=0.0001 vs placebo), which includes work-related actions. The HDM SLIT-tablet is home-administered and associated with considerably fewer doctor's office visits, contributing to less workplace productivity loss versus SCIT. The additional productivity loss of SCIT and SLIT-tablet due to related doctor visits are $1,147 and $80, respectively. Conclusions Uncontrolled allergic rhinitis is associated with workplace productivity loss. HDM SLIT-tablet offers an AIT treatment option that demonstrates improved RQLQ and contributes to decreased productivity loss. Furthermore, the home-administration of SLIT-tablet optimizes productivity versus SCIT because of fewer visits to the doctor.

SQ HOUSE DUST MITE SUBLINGUAL IMMUNOTHERAPY TABLET IS WELL TOLERATED IN SUBJECTS WITH ALLERGIC ASTHMA

Introduction Asthma is a risk factor for systemic allergic reactions to subcutaneous immunotherapy. The safety of SQ house dust mite (HDM) sublingual immunotherapy (SLIT)-tablet in subjects with or without asthma was evaluated. Methods Safety data from 6 phase II/III double-blind, placebo-controlled trials of SQ HDM SLIT-tablet for the treatment of allergic rhinitis or mild-to-moderate asthma were pooled and compared between subjects with and without reported asthma. IRB approval was obtained. Data for the 12 SQ-HDM dose approved in Europe/US are presented. Results In all, 3473 subjects were randomized to 12 SQ-HDM (n=1663) or placebo (n=1810), 2036 (59%) of whom had reported asthma. Most asthma was moderate according to GINA criteria (66%, 12 SQ-HDM; 70%, placebo). The proportion of subjects reporting treatment-emergent adverse events (AEs) was similar between subjects with and without asthma (86% vs 85%, respectively) in the 12 SQ-HDM group and in the placebo group (70% vs 64%, respectively). The frequencies of treatment-related AEs, discontinuations due to AEs, severe AEs, and serious AEs were generally similar for subjects with and without asthma. One treatment-related systemic allergic reaction was reported; this event occurred in a subject without asthma. The frequency of asthma events in subjects with asthma was 11% with 12 SQ-HDM and 10% with placebo; in subjects without asthma the frequency was Conclusions SQ HDM SLIT-tablet was well tolerated and did not appear to increase asthma events in patients with mild-to-moderate asthma. The safety profile was comparable for subjects with HDM-induced respiratory allergy irrespective of asthma status. Asthma is a risk factor for systemic allergic reactions to subcutaneous immunotherapy. The safety of SQ house dust mite (HDM) sublingual immunotherapy (SLIT)-tablet in subjects with or without asthma was evaluated. Safety data from 6 phase II/III double-blind, placebo-controlled trials of SQ HDM SLIT-tablet for the treatment of allergic rhinitis or mild-to-moderate asthma were pooled and compared between subjects with and without reported asthma. IRB approval was obtained. Data for the 12 SQ-HDM dose approved in Europe/US are presented. In all, 3473 subjects were randomized to 12 SQ-HDM (n=1663) or placebo (n=1810), 2036 (59%) of whom had reported asthma. Most asthma was moderate according to GINA criteria (66%, 12 SQ-HDM; 70%, placebo). The proportion of subjects reporting treatment-emergent adverse events (AEs) was similar between subjects with and without asthma (86% vs 85%, respectively) in the 12 SQ-HDM group and in the placebo group (70% vs 64%, respectively). The frequencies of treatment-related AEs, discontinuations due to AEs, severe AEs, and serious AEs were generally similar for subjects with and without asthma. One treatment-related systemic allergic reaction was reported; this event occurred in a subject without asthma. The frequency of asthma events in subjects with asthma was 11% with 12 SQ-HDM and 10% with placebo; in subjects without asthma the frequency was SQ HDM SLIT-tablet was well tolerated and did not appear to increase asthma events in patients with mild-to-moderate asthma. The safety profile was comparable for subjects with HDM-induced respiratory allergy irrespective of asthma status.

SAFETY OF FIRST DOSE OF SQ HOUSE DUST MITE SUBLINGUAL IMMUNOTHERAPY TABLET IN CLINICAL TRIALS

Introduction Supervision in the physician's office for 30 minutes following the first dose of SQ house dust mite (HDM) sublingual immunotherapy (SLIT)-tablet is required to monitor for potential adverse reactions. Clinically important adverse events (AEs) occurring in connection to administration of the first dose were evaluated. Methods Safety data from 14 DBPC trials (N=6784) of SQ HDM SLIT-tablet were analyzed for clinically important treatment-related AEs associated with the first dose. IRB approval was obtained. Data for the Europe/US approved dose of 12 SQ-HDM (N=2139) are presented. Results The majority of treatment-related AEs with the first dose were mild or moderate local allergic reactions. In all, 2/2139 (0.09%) subjects experienced AEs requiring treatment with epinephrine within minutes of administration of the first dose. One subject developed laryngeal edema assessed as mild by the investigator, which was treated with epinephrine and resolved after 30 minutes; the subject completed the trial. The other subject discontinued treatment after experiencing a systemic allergic reaction (reported as moderate hypersensitivity), which was treated with epinephrine and resolved after 1 hour. Four additional subjects discontinued treatment on day 1 due to AEs, mainly mild/moderate local allergic reactions, all of which resolved within 2 hours. No late-phase allergic reactions occurred. No serious AEs related to first dose were observed. Conclusions Clinically important AEs related to the first dose of SQ HDM SLIT-tablet occurred within minutes and were manageable with conventional allergy pharmacotherapy.

ADVERSE EVENT PROFILE OF SQ HOUSE DUST MITE SUBLINGUAL IMMUNOTHERAPY TABLET AFTER TREATMENT INTERRUPTION

Introduction The SQ house dust mite (HDM) sublingual immunotherapy (SLIT)-tablet is approved for daily administration for the treatment of HDM-induced allergic rhinitis. The adverse event (AE) profile following treatment interruption was evaluated. Methods Safety data from 2 DBPC trials were pooled and analyzed for AEs reported at any point after a treatment interruption of ≥ 2 consecutive days for any reason. Data for the Europe/US approved dose 12 SQ-HDM (n=783) and placebo (n=782) are presented. IRB approval was obtained. Results In all, 977/1565 subjects (62%; 476/783, 12 SQ-HDM; 501/782, placebo) reported a treatment interruption for any reason. Median interruption duration was 7 days for 12 SQ-HDM and 8 days for placebo. The proportion of subjects who experienced AEs at any point after treatment re-initiation was similar between 12 SQ-HDM (226/783 [29%]) and placebo (203/782 [26%]). Most AEs after treatment re-initiation were assessed by the investigator as mild or moderate in severity. No systemic allergic reactions, epinephrine administrations, or severe local swellings were reported after treatment re-initiation. In the 12 SQ-HDM group, the most frequently reported AEs after re-initiation were oral pruritus (8%), throat irritation (8%), and ear pruritus (7%); the frequencies of these AEs with placebo were 1%, 2%, and 1%, respectively. This AE profile characterized by local application site reactions is consistent with the known safety profile of the SQ HDM SLIT-tablet. Conclusions Safety data after short-term interruption of SQ HDM SLIT-tablet treatment do not indicate a safety signal after tablet re-initiation. The safety profile after long-term treatment interruption was not determined.

Efficacy and safety of SQ house dust mite sublingual immunotherapy-tablet in Japanese children.

The SQ house dust mite (HDM) sublingual immunotherapy (SLIT)-tablet (TO-203, Torii, Japan/ALK, Denmark) treatment has been effective against respiratory allergic diseases in patients aged ≥12years during European, Japanese, and North American trials. This trial was conducted to investigate the efficacy and safety of this treatment in Japanese children (5-17years) with moderate-to-severe HDM allergic rhinitis (AR). In this randomized, double-blind, placebo-controlled trial, 458 Japanese children were randomly assigned to a daily SQ HDM SLIT-tablet [10000 Japanese Allergy Unit (JAU), equivalent to 6 SQ-HDM in Europe and the US] or placebo (1:1) treatment for 1year. Inclusion required an AR symptom score of ≥7 on at least 7days during a 14-day run-in period while symptomatic treatment was withdrawn. The primary endpoint was the total combined rhinitis score (TCRS) comprising AR symptom and medication scores during the last 8weeks of the treatment period. The analysis of primary endpoint demonstrated statistically significant absolute reduction in TCRS of 1.22 with a relative difference of 23% (95% confidence interval, 14% to 31%) in the 10000 JAU compared with placebo. Predefined stratified analyses revealed the same degree of efficacy of 1.11 (P=0.002), 21% (8% to 32%) and 1.36 (P=0.001), 26% (11% to 38%), respectively, in pediatric (5-11years) and adolescent subjects (12-17years). The treatment was well tolerated by both pediatric and adolescent subjects. This trial, for the first time, demonstrated the efficacy and safety of the HDM SLIT-tablet in pediatric patients with moderate-to-severe HDM AR (JapicCTI-152953).