SQ House Dust Mite SLIT-tablet Research Articles

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.

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 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.

The SQ House Dust Mite SLIT-Tablet Is Well Tolerated in Patients with House Dust Mite Respiratory Allergic Disease

Background: The SQ house dust mite (HDM) SLIT-tablet (ALK, Denmark) addresses the underlying cause of HDM respiratory allergic disease, and a clinical effect has been demonstrated for both HDM allergic rhinitis and allergic asthma. Here, we present pooled safety data from an adult population with HDM respiratory allergy, with particular focus on the impact of asthma on the SQ HDM SLIT-tablet tolerability profile. Methods: Safety data from 2 randomised double-blind, placebo-controlled clinical trials were included: MT-04: 834 adults with HDM allergic asthma not well controlled by inhaled corticosteroids and with HDM allergic rhinitis, and MT-06: 992 adults with moderate-to-severe HDM allergic rhinitis despite the use of allergy pharmacotherapy and with or without asthma. Results: The proportion of subjects experiencing adverse events (AEs) was greater in the active treatment group (12 SQ-HDM; 73% of subjects) compared to placebo (53%). The most common treatment-related AEs were local allergic reactions. No AEs were reported as systemic allergic reactions. Regardless of asthma status, most AEs were mild or moderate (>97% of AEs) and the frequency of serious AEs was low. Subgroup analysis revealed no statistically significant difference in the risk of experiencing moderate or severe treatment-related AEs for subjects with asthma compared to subjects without asthma (p = 0.88). In addition, subjects with partly controlled or uncontrolled asthma were no more likely to experience moderate or severe treatment-related AEs than subjects with controlled asthma (p = 0.42). Conclusion: The SQ HDM SLIT-tablet is well tolerated, and the safety profile was comparable for subjects with HDM respiratory allergic disease irrespective of asthma status.

Cost-effectiveness of SQ® HDM SLIT-tablet in addition to pharmacotherapy for the treatment of house dust mite allergic rhinitis in Germany.

BackgroundAllergic rhinitis is a global health problem that burdens society due to associated health care costs and its impact on health. Standardized quality (SQ®) house dust mite (HDM) sublingual immunotherapy (SLIT)-tablet is a sublingually administered allergy immunotherapy tablet for patients with persistent moderate to severe HDM allergic rhinitis despite use of allergy pharmacotherapy.ObjectiveTo assess the cost-effectiveness of SQ HDM SLIT-tablet in Germany for patients suffering from HDM allergic rhinitis.MethodsA pharmacoeconomic analysis, based on data collected in a double-blinded, phase III randomized placebo-controlled trial (n=992), was undertaken to compare SQ HDM SLIT-tablet in addition to allergy pharmacotherapy to placebo plus allergy pharmacotherapy. Quality-adjusted life year (QALY) scores and health care resource use data recorded in the trial were applied to each treatment group and extrapolated over a nine-year time horizon. A series of scenarios were used to investigate the impact of changes on long-term patient health for both treatment groups, which was measured by annual changes in QALY scores. Deterministic and probabilistic sensitivity analyses were also performed.ResultsIn the base case analysis, compared with allergy pharmacotherapy, SQ HDM SLIT-tablet led to a QALY gain of 0.31 at an incremental cost of €2,276 over the nine-year time horizon, equating to an incremental cost-effectiveness ratio of €7,519. The treatment was cost-effective for all scenarios analyzed; however, results were sensitive to changes in individual parameter values during the deterministic sensitivity analysis.ConclusionSQ HDM SLIT-tablet in addition to pharmacotherapy is cost-effective compared with allergy pharmacotherapy plus placebo for the treatment of persistent moderate to severe HDM allergic rhinitis that is not well controlled by allergy pharmacotherapy.

Long-term effects of a house dust mite sublingual immunotherapy tablet in an environmental exposure chamber trial

BackgroundTreatment with SQ house dust mite (HDM) sublingual immunotherapy (SLIT) tablet is effective for HDM respiratory allergic disease, but data on long-term effects are lacking. ObjectivePost hoc analyses were conducted to determine the long-term effect of SQ HDM SLIT-tablet on nasal, ocular, and cough symptoms 1 year after discontinuation of treatment. MethodsStudy participants underwent environmental exposure chamber (EEC) challenges at baseline and week 24 in a randomized, placebo-controlled, double-blind trial (NCT01644617) during which participants received daily 12 SQ-HDM, 6 SQ-HDM, or placebo for 24 weeks. Asthma had to be stable, well controlled, and nonsevere. The mean total asthma symptom score (TASS; sum of 3 symptoms: cough, wheeze, and dyspnea) during baseline and week 24 EEC challenge was analyzed in all participants who completed the trial (n = 106). Approximately 1 year after trial completion, another EEC challenge was conducted in a subset of participants (n = 51). Total nasal symptom score (sum of 4 symptoms), total ocular symptom score (sum of 2 symptoms), and cough were assessed. ResultsCompared with baseline and end-of-treatment values, sustained improvement of all symptoms assessed at the 1-year follow-up EEC challenge was evident in participants treated with 12 SQ-HDM. Results with 6 SQ-HDM were less notable. After 24 weeks of 12 SQ-HDM, TASS during EEC challenge was improved 65% vs baseline; at 1-year follow-up, cough was improved 57% vs baseline. ConclusionPersistent improvement of nasal and ocular symptoms was observed up to 1 year after completing 24 weeks of 12 SQ-HDM treatment. Beneficial effects on cough were also observed. Trial Registrationclinicaltrials.gov Identifier NCT01644617.

Major allergen content consistency of SQ house dust mite sublingual immunotherapy tablets and relevance across geographic regions

BackgroundConsistency in composition and potency, particularly regarding major allergens, is crucial for the quality of extracts for allergen immunotherapy. ObjectiveTo characterize the major allergen composition of house dust mite (HDM) extracts commercially available in the United States and the SQ HDM sublingual immunotherapy (SLIT) tablet, and to relate the composition to patient sensitization patterns. MethodsDer 1/Der 2 ratios were determined in 10,000- and 30,000-AU/mL HDM extracts from 5 US companies and the SQ HDM SLIT-tablet. Allergen content was analyzed by enzyme-linked immunosorbent assay and compared with an in-house reference. Sensitivity toward Der p 1, Der p 2, and Der p 10 was determined in serum from randomly selected subgroups of 220 individuals from North American and European SQ HDM SLIT-tablet trials. ResultsMean Der 1/Der 2 ratios in US HDM extracts ranged from 0.4 to 20.5. For the SQ HDM SLIT-tablet (20 batches), variability did not exceed 12% regarding content of Der f 1 (SD, 11.9%; 95% confidence interval [CI], 0.94–1.06), Der p 1 (SD, 6.1%; 95% CI, 0.97–1.03), and combined Der 2 allergen (SD, 6.4%; 95% CI, 0.97–1.03), indicating a consistent Der 1/Der 2 ratio. High allergen sensitivity frequencies toward Der p 1 and Der p 2 were observed regardless of geographic region. Efficacy of the SQ HDM SLIT-tablet has been demonstrated in 5 clinical trials. ConclusionThe SQ HDM SLIT-tablet has efficacy potential for a broad range of patients because it includes a consistent 1:1 ratio of the 2 major HDM allergens to which individuals were most frequently sensitized across geographic regions. Efficacy has been demonstrated.

Efficacy of house dust mite sublingual immunotherapy tablet in North American adolescents and adults in a randomized, placebo-controlled trial

The house dust mite (HDM) sublingual immunotherapy (SLIT) tablet (MK-8237; Merck & Co, Kenilworth, NJ/ALK-Abelló, Hørsholm, Denmark) has demonstrated beneficial effects on allergic rhinoconjunctivitis and asthma outcomes in European trials. This is the first trial to assess the efficacy/safety of HDM SLIT-tablets in North American subjects with HDM-induced allergic rhinitis with or without conjunctivitis (AR/C). In this double-blind, multicenter trial (NCT01700192) 1482 subjects (aged ≥12years) with HDM-induced AR/C with or without asthma were randomized to a daily SQ HDM SLIT-tablet (12 SQ-HDM dose) or placebo for up to approximately 52weeks. Arhinitis daily symptom score (DSS; 4 nasal symptoms, maximum score=12) of 6 or greater, or 5 or greater with 1 symptom being severe, on 5 of 7 consecutive days before randomization was required. The primary end point was the average total combined rhinitis score, which was defined as the rhinitis DSS plus rhinitis daily medication score (DMS), during the last 8 treatment weeks. Treatment with 12 SQ-HDM improved the total combined rhinitis score by 17% (95% CI, 10% to 25%) versus placebo. Improvements versus placebo in the secondary end points of average rhinitis DSS, rhinitis DMS, total combined rhinoconjunctivitis score, and visual analog scale-assessed AR/Csymptoms were 16%, 18%, 17%, and 16%, respectively. All nominal P values were less than .001 versus placebo, except rhinitis DMS (P=0.15). No treatment-related adverse events meeting the International Council on Harmonizationdefinition of a serious adverse event were reported; 1 nonserious treatment-related systemic allergic reaction occurred (assessed as moderate intensity) at first administration under medical supervision and was treated with epinephrine. In the first North American trial of use of a SLIT-tablet for HDM allergy, 12 SQ-HDM was well tolerated and improved HDM-induced rhinitis symptoms in adults and adolescents.

Efficacy and safety of SQ house dust mite (HDM) SLIT-tablet treatment of HDM allergic asthma

ABSTRACTIntroduction: In the treatment of house dust mite (HDM) respiratory allergic disease, allergy immunotherapy constitutes an add-on treatment option targeting the underlying immunological mechanisms of allergic disease. However, for the treatment of HDM allergic asthma, the use of subcutaneous allergy immunotherapy (SCIT) has been limited by the risk of systemic adverse events. Thus, sublingually administered allergy immunotherapy (SLIT) has been investigated as a treatment option with an improved tolerability profile that allows for safer treatment of patients with HDM allergic asthma.Areas covered: In this Drug Profile, we provide a review of the clinical data behind the SQ HDM SLIT-tablet, which was recently approved for the treatment of HDM allergic asthma and allergic rhinitis by regulatory authorities in several European countries.Expert commentary: The SQ HDM SLIT-tablet is the first allergy immunotherapy to be tested prospectively in patients with asthma, and to favorably modify patient relevant end points such as requirement for inhaled corticosteroid (ICS) or the time to first asthma exacerbation upon ICS reduction, suggesting that SQ HDM SLIT-tablet treatment may contribute to improving overall asthma control.

Fractionation of Source Materials Leads to a High Reproducibility of the SQ House Dust Mite SLIT-Tablets

Background: The production of house dust mite (HDM) allergen products for allergy immunotherapy has traditionally been based on purified mite bodies or whole-mite culture, which are quite different source materials with a limited possibility for adjusting the chemical composition. The SQ HDM SLIT-tablet is a fast-dissolving pharmaceutical formulation that has been developed for sublingual immunotherapy (SLIT) of HDM respiratory allergic disease. Objective: The objective of the present study was to establish a process for the production of drug substances for the SQ HDM SLIT-tablet offering a high reproducibility and independent control of the major allergens. Methods: Process controls were documented in a comprehensive process parameter qualification. The analyses comprised composition by crossed immunoelectrophoresis, protein content by BCA, total IgE binding potency by Centaur assay, quantitative major allergen determination by radial immunodiffusion and ELISA, and the ranking of emPAI scores generated by mass spectrometry. Results: Analysis of 20 batches of final product yielded a normalized mean and standard deviation for IgE binding potency of 100 ± 4.5. The standard deviation in the contents of Der f 1 and Der p 1 were correspondingly 11.9 and 6.1, whereas the variation in the group 2 major allergen content was 6.4. All measured 95% confidence limits between batches were less than 12%. Conclusions: The production process for the SQ HDM SLIT-tablet based on the separation of source material into four fractions each enriched in one major allergen enables precise adjustment of the relative major allergen content and high reproducibility of the final product.

SQ house dust mite (HDM) SLIT-tablet provides clinical improvement in HDM-induced allergic rhinitis

ABSTRACTHouse dust mite (HDM) allergy represents a highly prevalent inhalant allergy, and exposure to HDM allergens results in allergic rhinitis with persistent symptoms that may not be adequately controlled with available allergy pharmacotherapy. Allergy immunotherapy constitutes a complementary treatment option targeting the underlying immunological mechanisms of allergic disease and represents the only treatment with a potential for disease modification and long-term efficacy. As traditional allergy immunotherapy delivered by subcutaneous injection of specific HDM allergens involves a time-consuming treatment regimen and a risk of systemic adverse reactions, sublingually administered allergy immunotherapy (SLIT) has been investigated as a more convenient treatment option with similar levels of efficacy and an improved safety profile that allows for at-home daily administration.In this Drug Profile, we provide a review of the clinical data behind the SQ HDM SLIT-tablet, which was recently approved for the treatment of HDM-induced allergic rhinitis by regulatory authorities in Europe and Japan.