SQ House Dust Mite 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.

Adverse Event Profile of SQ House Dust Mite Sublingual Immunotherapy Tablet After Longer Treatment Interruption

Treatment interruptions to sublingual immunotherapy (SLIT)-tablets are sometimes necessary, such as after oral surgery. To assess the association between treatment interruption of house dust mite (HDM) SLIT-tablet and adverse events (AE), 3 methods of risk assessment were used.

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.

Safety of Dual Sublingual Immunotherapy with Japanese Cedar Pollen and SQ House Dust Mite Tablets in Children, Adolescents and Adults

Safety of Dual Sublingual Immunotherapy with Japanese Cedar Pollen and SQ House Dust Mite Tablets in Children, Adolescents and Adults

SQ house dust mite sublingual immunotherapy for the treatment of adults with house dust mite-induced allergic rhinitis

ABSTRACTIntroduction: Allergic rhinitis (AR) is one of the most common chronic conditions affecting both children and adults. The house dust mites (HDM) account for a substantial part of the overall sources of allergens. In patients where allergen avoidance and symptom-relieving pharmacotherapy do not provide adequate disease control, specific allergen immunotherapy (AIT) is indicated. While subcutaneous injection (SCIT) is considered as a time-consuming and invasive treatment regimen, sublingual allergy immunotherapy (SLIT) appears as more convenient treatment strategy.Areas covered: This Drug Profile reviews the clinical data behind the development of the SQ HDM SLIT-tablet, including both the early studies and the pivotal studies, which formed the basis for regulatory approval in Europe, Japan, and the U.S.Expert opinion: The clinical trials behind the development of the SQ HDM-SLIT have demonstrated that the tablet provides a safe, well-tolerated and robust efficacy in the treatment of HDM-induced allergic rhinoconjunctivitis. Further, studies show that the SQ HDM SLIT-tablet is a cost-effective treatment option compared with SCIT.

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

BackgroundThere 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. MethodsThis 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. ResultsThe 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. ConclusionsDual 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.

Sublingual immunotherapy tablet for the treatment of house dust mite allergic rhinitis in Canada: an alternative to minimize treatment costs?

BackgroundA cost-minimization analysis (CMA) was performed to estimate the economic impact of introducing the SQ house dust mite sublingual immunotherapy (SQ HDM SLIT)-tablet marketed as ACARIZAX™ (regulatory approval May 2017) for the treatment of HDM-induced allergic rhinitis in Canada (Ontario and Quebec), where house dust mite subcutaneous immunotherapy (HDM SCIT) is already an available treatment option.MethodsA CMA was deemed appropriate and was based on the assumption that the SQ HDM SLIT-tablet has comparable efficacy to HDM SCIT. A societal perspective was adopted in the model, including relevant costs of medications, health care services and productivity loss. A 3 year time horizon was used corresponding to a recommended treatment course of allergy immunotherapy. Resource use and costs were based on published sources, where possible, and validated and complemented by a Canadian specialist clinician (allergist) in active practice in Ontario and in Quebec, respectively, where applicable. A discount rate of 1.5% was applied in accordance with the Canadian Agency for Drugs and Technologies in Health (CADTH) guidelines. To assess the robustness of the results, sensitivity analyses were performed by testing alternative assumptions for selected parameters, to understand their impact on the results of the analysis.ResultsThe direct treatment costs for a 3-year treatment with SQ HDM SLIT-tablets were higher than for HDM SCIT for both provinces, Ontario and Quebec ($4732.12 and $4829.03 vs. $3434.51 and $2987.74). However, when adding the indirect costs to the model, total savings for the treatment with SQ HDM SLIT-tablets of $1833.00 for Ontario and $769.03 for Quebec were observed. Sensitivity analyses with varying HDM SCIT resource use, discount rates, titration and maintenance injections, nurse time, and number of injections per vial resulted in savings of SQ HDM SLIT-tablets over HDM SCIT in all scenarios analysed.ConclusionsThe CMA indicates that SQ HDM SLIT-tablets are a cost-minimizing alternative to HDM SCIT when considered from a societal perspective in Ontario and Quebec.

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.

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).

SQ house dust mite sublingual immunotherapy tablet subgroup efficacy and local application site reaction duration

BackgroundAllergic rhinitis with or without conjunctivitis (AR/C) is common, necessitating evaluation of SQ house dust mite (HDM) sublingual immunotherapy (SLIT)-tablet efficacy in various subgroups. ObjectiveTo evaluate 12 SQ-HDM efficacy and safety across subgroups, and the onset, duration, and recurrence of local application site reactions. MethodsSubgroup (age, sex, race, asthma status, and allergen sensitization) efficacy was assessed using pooled data from 2 previously described trials of daily 12 SQ-HDM vs placebo for AR/C (n = 2,138). Efficacy was measured by average total combined rhinitis score (TCRS; rhinitis daily symptom plus medication score) during the last 8 weeks of treatment. Safety in subgroups and local application site reaction onset, duration, and recurrence were evaluated using pooled data from 5 previously described trials of SQ HDM SLIT-tablet (n = 2,923). ResultsSignificant (based on 95% confidence intervals [CIs]) reduction in TCRS was seen with 12 SQ-HDM relative to placebo across all subgroups, with TCRS improvements ranging from 15% to 25%. The AE profile was generally similar within subgroups. Approximately 95% of local application site reactions were mild to moderate in severity. Median duration on day 1 of treatment for the most common local application site reactions (throat irritation, oral pruritus, ear pruritus, and lip swelling) ranged from 30 to 60 minutes; median first day of onset ranged from days 1 to 4 of treatment; median days that reactions recurred ranged from 3 to 12 days. ConclusionTreatment with 12 SQ-HDM consistently improved symptoms and was well tolerated in relevant subgroups of subjects with HDM AR/C. Local application site reactions to 12 SQ-HDM were typically mild to moderate and transient.

Treatment with the SQ house dust mite sublingual immunotherapy tablet may be initiated year-round

Treatment with the SQ house dust mite sublingual immunotherapy tablet may be initiated year-round

Impact of Adverse Event Solicitation on the Safety Profile of SQ House Dust Mite Sublingual Immunotherapy Tablet

It has been recommended that sublingual immunotherapy (SLIT) safety be assessed using solicited adverse event (AE) collection methods. The objectives of this study were to describe the impact on the safety profile of SQ house dust mite (HDM) SLIT-tablet (12 SQ-HDM dose) when prespecified local application site reactions were solicited versus unsolicited, and discuss ramifications of AE solicitation. Subjects were randomized to daily 12 SQ-HDM or placebo for up to 52 weeks in 4 double-blinded, multicenter trials. In one trial (NCT01700192; N= 1272), subjects documented daily the presence or absence of 15 World Allergy Organization-defined local application site reactions using a structured questionnaire of closed-ended questions (solicited AEs). Subjects in the other trials were not asked about specific AEs (unsolicited AEs), and AE data were pooled (N= 1287). Analysis was limited to adults aged 18 to 65 years. Whether AEs were solicited or unsolicited, the most common AEs leading to study discontinuation with 12 SQ-HDM were throat irritation and oral pruritus. Approximately 95% of treatment-related AEs were mild to moderate. Placebo-subtracted frequencies of local application site reactions associated with 12 SQ-HDM were higher when solicited versus unsolicited (ie, throat irritation, 46% vs 13%, respectively; oral pruritus, 47% vs 17%; ear pruritus, 40% vs 4%; mouth swelling, 8% vs 2%; tongue ulceration, 10% vs 0%; mouth ulceration, 7% vs <1%). Qualitatively, the safety profile of 12 SQ-HDM was similar when AEs were solicited versus unsolicited; hence, solicitation did not alter the safety profile. Higher observed frequencies of local application site reactions with AE solicitation may be partly due to suggestive reporting bias, as observed in placebo-treated subjects.