Dust Mite Sublingual Immunotherapy Tablet Research Articles

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.

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)

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.

Efficacy of Sublingual Immunotherapy Tablets for Allergic Rhinoconjunctivitis in Adult Monosensitized and Polysensitized Subjects

Most patients with allergic rhinitis/conjunctivitis (AR/C) are sensitized to more than one allergen. This analysis evaluated the efficacy of grass, ragweed, tree, and house dust mite (HDM) sublingual immunotherapy (SLIT) tablets in adults who are monosensitized or polysensitized.

Efficacy and safety of house dust mite sublingual immunotherapy tablets in allergic rhinitis: A systematic review and meta-analysis

BackgroundHouse dust mite (HDM) sublingual immunotherapy (SLIT) tablets have been approved for the treatment of patients with allergic rhinitis (AR). However, the meta-analysis on the efficacy of HDM-SLIT tablets for HDM-induced AR patients remained limited. MethodsFive databases were searched including: PubMed/MEDLINE, EMBASE, Web of Science, the Cochrane Central Register of Controlled Trials, and CINAHL for randomized controlled trials (RCTs) that addressed the efficacy and safetyof HDM-SLIT tablets compared with placebo until January 2022. The primary outcome was a combined symptom and medication score (CSMS) after treatment. ResultsEight eligible RCTs were identified with a total of 3601 patients treated with HDM-SLIT tablets and 2783 patients who received a placebo. The CSMS was significantly lower in the HDM-SLIT tablet group compared with the placebo (standardized mean difference (SMD) −0.28 [95% CI: −0.32 to −0.23]). There was a significant reduction in rhinitis symptom scores, rhinitis medication scores, total combined conjunctivitis scores, and rhinoconjunctivitis quality of life questionnaire scores. The consistent efficacy compared to the placebo has been exhibited over the different kinds and doses of HDM tablets (6 SQ, 12 SQ, 300 IR, and 500 IR) and age groups (>5 years old, adolescents and adults) with low degrees of variability across the studies. There was no significant difference in proportions of participants who were injected with epinephrine between the treatment- and placebo groups. ConclusionsHDM-SLIT tablet is an effective treatment in reducing rhinitis symptoms and medication use in AR patients with favorable safety. They also improve quality of life and conjunctivitis symptoms.

Efficacy of a house dust mite sublingual immunotherapy tablet as add-on dupilumab in asthma with rhinitis

BackgroundHDM SLIT is one of the disease-modifying treatment for allergic asthma, and has demonstrated efficacy in clinical trials. Dupilumab, blocks IL-4 and IL-13 signaling, key drivers of type 2 inflammation, and is approved for patients with uncontrolled, moderate-to-severe asthma. The aim of this study was to evaluate outcomes after HDM SLIT initiation in asthma with rhinitis not optimally controlled with dupilumab in a real-world setting. MethodsAt baseline and 48 weeks after treatment, asthma control questionnaire (ACQ)-5, asthma quality of life questionnaire (AQLQ) and rhinoconjunctivitis quality of life questionnaire (RQLQ) were assessed. Spirometry, type 2 inflammatory biomarkers and quantitative computed tomographic parameters of airway remodeling were also collected. ResultsOf 47 patients received HDM SLIT and 41 completed the study. Combined HDM SLIT and dupilumab improved ACQ-5 (p < 0.05), AQLQ (p < 0.05), RQLQ (p < 0.05), and increased lung function and reduced FeNO (p < 0.05) and airway percentage wall area, and wall thickness (each, p < 0.05). The change in ACQ-5 and AQLQ score correlated with both changes in FeNO and FEV1 percent predicted. Multiple regression analysis showed that the change in FEV1 percent predicted was independent factor for improvement of AQLQ (r2 = 0.510, p = 0.012). Based on ROC analysis for predicting SLIT responders, the baseline area under the curves in serum HDM specific-IgE, total IgE and FEV1 percent predicted were high (>0.8). ConclusionsThese results support the benefits of adding HDM SLIT to pharmacotherapy plus dupilumab in uncontrolled asthma with rhinitis.

Efficacy and Safety of House Dust Mite Sublingual Immunotherapy Tablet in Allergic Asthma: A Systematic Review of Randomized Controlled Trials

House dust mite sublingual immunotherapy (HDM SLIT) effectively treats allergic rhinitis (AR). However, the evidence of HDM SLIT for allergic asthma remained limited. To systematically review the efficacy and safety of HDM SLIT tablets in patients with allergic asthma. We performed a systematic search through PubMed, Scopus, EMBASE, Web of Science, the Cochrane Center of Controlled Trials, and Google Scholar for randomized controlled trials (RCTs) that addressed the efficacy and safety of HDM SLIT tablets compared with placebo or no intervention in allergic asthma from their inception date until September 2021. The primary outcome was the reduction in inhaled corticosteroids (ICS) dose. Additional outcomes were asthma control, exacerbation, lung function, quality-of-life, and adverse events. There were 7 RCTs, 5 studies in allergic asthma (4 in adults and 1 in children), and 2 in AR with or without asthma. The 6 standardized quality (SQ) HDM effectively reduced ICS dose in well- to partly controlled mild-to-moderate asthma in 1 RCT. Two RCTs evaluated the efficacy of 6 SQ and 12 SQ HDM in reducing asthma exacerbation in partly controlled moderate-to-severe asthma, and their results were inconsistent. One study in children with mild-to-moderate asthma found no benefit of HDM SLIT. Two RCTs in AR with or without mild-to-moderate asthma showed improvement of asthma symptoms. Adverse events were primarily local, and anaphylaxis treated with epinephrine was reported in 3 patients. The HDM SLIT tablets tend to effectively reduce ICS use in adults and adolescents with well- to partly controlled mild-to-moderate allergic asthma with a favorable safety profile.

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.

Which patients with asthma are most likely to benefit from allergen immunotherapy?

If allergen immunotherapy (AIT) is to be considered as a treatment option for allergic asthma, it must undergo the same developmental steps as other antiasthmatic drugs. The bronchial allergen challenge model has demonstrated excellent negative predictive value for the development of new therapies for asthma. Subcutaneous immunotherapy appears to have a clinical and significant effect on the early asthmatic response to mite, cat, and birch and grass pollens in children and adults. Use of AIT in children with asthma is widely practiced but not supported by as strong a level of evidence as in adults. House dust mite sublingual immunotherapy tablets demonstrate efficacy in asthma exacerbations and other outcomes when used as add-on therapy in adult patients. Using a biologic to improve the patient's lung functions and asthma control before initiating AIT can transform unsuitable candidates for AIT into appropriate candidates. Because AIT is a form of personalized medicine, phenotyping the most suitable patient is necessary. Field studies of adults and children have suggested that polysensitized patients with rhinitis and Global Initiative for Asthma class 2 to class 4 asthma appear the most likely to be good responders. We hypothesized that AIT responders are those who demonstrate a high eosinophilic response to natural or experimental exposure.

Safety and tolerability of the standardized quality house dust mite sublingual immunotherapy tablet in real life: A noninterventional, open-label study

House dust mites (HDMs) are a major source of indoor allergens and an important factor for triggering airway diseases such as allergic rhinitis (AR) and allergic asthma (AA). The worldwide prevalence of sensitization to HDM is high and is estimated to affect 1% to 2% of the global population.1 In Germany, about 16% of the adult population is sensitized to HDMs.2

No Severe Anaphylaxis in Clinical Trials of House Dust Mite Sublingual Immunotherapy Tablet Using a Standardized Identification Algorithm

A standardized anaphylaxis definition is needed for clinical trials of allergy immunotherapy products. An algorithm in the Standardized MedDRA Query (SMQ) was used to identify anaphylaxis in house dust mite (HDM) sublingual immunotherapy (SLIT)-tablet clinical trials.

Successful treatment of atopic dermatitis with house dust mite sublingual immunotherapy tablets.

Atopic dermatitis (AD) is the most common chronic inflammatory skin disease. Allergen-specific immunotherapy is a treatment option for selected patients with severe AD sensitization to house dust mites (HDM). To report the first case of successful treatment with HDM sublingual immunotherapy (SLIT) tablets in patients with severe AD. A Thai male patient with HDM sensitization and severe AD who had not responded to topical corticosteroids and calcineurin inhibitors underwent 1 month of HDM subcutaneous immunotherapy (SCIT), after which his skin symptoms were minimally improved. He lost follow-up SCIT and the symptoms worsened, with large wheal lesions appearing at the SCIT injection site, so we decided to switch from SCIT to HDM SLIT tablets. After the SLIT treatment, the AD and skin lesions improved and the medication could be stopped. HDM SLIT might be an alternative treatment in patients with HDM sensitization and severe AD who are refractory to conventional treatment.

Utility of Environmental Exposure Unit Challenge Protocols for the Study of Allergic Rhinitis Therapies.

This paper explores how the Environmental Exposure Unit (EEU) experimental model can be used to further our understanding of pharmacotherapies and immunotherapies for the treatment of allergic rhinitis (AR). EEUs are used increasingly for the study of combination therapies, immunotherapies, and novel AR treatments. A combined antihistamine/corticosteroid nasal spray formulation was seen to have a faster onset of action relative to the therapies individually in the Environmental Exposure Chamber. House dust mite sublingual immunotherapy tablets are both safe and efficacious as evaluated by the Vienna Challenge Chamber. The Kingston EEU found that a novel peptide-based immunotherapy approach to be effective in reducing grass pollen-induced AR. Lastly, nasal filters were determined to reduce seasonal AR symptoms, given out-of-season in the Denmark Environmental Exposure Unit. EEUs are controlled, replicable models that provide valuable insight into the efficacy, onset and duration of action, and dose-related impacts of AR therapeutics, with direct clinical relevance.

Efficacy and Safety of HDM SLIT Tablet in Japanese Adults with Allergic Asthma

The standardized quality (SQ) house dust mite (HDM) sublingual immunotherapy (SLIT) tablet has demonstrated efficacy and safety for allergic asthma (AA) in European trials. To evaluate the efficacy and safety of SQ HDM SLIT tablet treatment for up to 19 months in Japanese adults with AA. In this randomized, double-blind, placebo-controlled trial, patients aged 18 to 64 years with AA were randomly assigned (1:1:1) to SQ HDM SLIT doses of 10,000 or 20,000 Japanese Allergy Unit or placebo. Subjects had Asthma Control Questionnaire score of 1.0 to 1.5 and daily inhaled corticosteroid use of 200 to 400 μg of fluticasone propionate at randomization. The primary end point was the time from randomization to the first asthma exacerbation as the inhaled corticosteroid dose was being reduced. Of the 826 randomized subjects, 693 (84%) completed the trial. No statistically significant differences between the active groups and the placebo group were observed for the primary or any other efficacy end points. However, post hoc analysis indicated a significant difference between the 20,000 Japanese Allergy Unit and placebo groups among subjects who used a short-acting β2-agonist during the baseline period (hazard ratio, 0.70; 95% CI, 0.48-1.00; P= .04997). No deaths or anaphylactic reactions were reported. Most adverse events were mild to moderate in severity. The trial demonstrated a favorable safety profile of the SQ HDM SLIT tablet in Japanese adult patients with AA. The treatment appeared to be efficacious in patients requiring rescue medication (ie, short-acting β2-agonist) at baseline in the efficacy assessment using asthma exacerbation during inhaled corticosteroid reduction (JapicCTI number 121847).

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.

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.

House Dust Mite Tablets Now Officially Accepted as Treatment in GINA: What Is the Evidence and What’s Next?

Purpose of Review This review analyzes the growing evidence regarding the standardized quality house dust mite (SQ-HDM) sublingual immunotherapy (SLIT) tablets as a valuable therapeutic option in asthma, as recently included in the treatment algorithm of the Global Initiative for Asthma (GINA) as an add-on treatment for adult patients with allergic asthma not well controlled with inhaled corticosteroids (ICS).

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.