House Dust Mite Sublingual Tablet Research Articles

Safety and effectiveness of a 300 IR house dust mite sublingual tablet: descriptive 4-year final analysis of a post-marketing surveillance in Japan.

Background: Data are limited for clinical outcomes with house dust mite (HDM) allergen immunotherapy beyond 2years' observation. Materials & methods: A post-marketing drug-use survey assessed the safety and effectiveness of the 300 index of reactivity (IR) HDM tablet during use forup to 4years in Japan. Results: 538 patients were evaluable for safety and 383 for effectiveness. Most adverse drug reactions (ADRs) occurred early and were local reactions; 5.6% of 249 total events were reported during years 2 to 4 as new ADRs after the interim analysis. The CAP-RAST score was identified as a potential risk factor for ADRs. The proportion of evaluable patients with severe allergic rhinitis symptoms decreased from 46.4% at baseline (n= 317) to 1.0% at 4years (n=104). Patients (n=16) who discontinued 300 IR HDM tablet due to symptomatic improvement had sustained improvement relative to baseline 1 to 2years later. Conclusion: Long-term use of the300 IR HDM tablet is safe and effective.

Efficacy of House Dust Mite Sublingual Tablet in the Treatment of Allergic Rhinoconjunctivitis: A Randomized Trial in a Pediatric Population

To investigate the efficacy, safety, and immunologic response of standardized sublingual house dust mite (HDM) tablets in Japanese pediatric patients.Included in the study were patients ≥5 and ≤16 years of age with allergic rhinitis symptoms for ≥2 years, a score of ≥3 on quantitative analysis of specific immunoglobulin E antibody to Dermatophagoides pteronyssinus and/or Dermatophagoides farinae antigens, positive nasal provocation test result for HDM, and Rhinitis Total Symptom Score ≥6 points per day for 7 days before randomization. Those with symptoms from other allergens, mild persistent or more-severe asthma, or inhaled corticosteroid use were excluded.This multicenter, double-blind, randomized placebo-controlled trial was conducted at 51 Japanese medical institutions from October 2015 to December 2016. Subjects were randomly assigned 1:1 to placebo or HDM tablets with an index of reactivity of 300 daily for 52 weeks. Symptoms and rescue medication use were recorded daily in a patient diary. The primary end point was the average adjusted symptom score for week 48 to 52, derived from daily Rhinitis Total Symptom Scores and adjusted for rescue medication use.Of 438 patients who were randomly assigned, 193 patients in the treatment group and 210 patients in the placebo group completed the study. The average adjusted symptom score was significantly lower in the treatment group compared with placebo (6.32 vs 7.27, P = .0005), with a least-squares mean difference of −13.1%. Improvement was seen at weeks 8 to 10 and was maintained throughout. Nasal Individual Symptom Scores were significantly lower in the treatment group, whereas Average Rescue Medication Scores and Ocular Individual Symptom Scores were not. Specific immunoglobulin E antibodies to HDM nearly doubled, whereas specific immunoglobulin G4 antibodies approximately tripled in the treatment group. Mild or moderate adverse events (oral pruritus, mouth edema, throat irritation, ear pruritus, and mouth swelling) occurred in most patients (96.8% of treated patients, 94.5% of placebo patients), typically from days 1 to 14. Two serious adverse events were reported in the placebo group and 6 were reported in the treatment group, leading to drug discontinuation in 1 patient with pseudocroup. Overall, 8% of randomly assigned patients discontinued the study, mostly because of adverse effects. There were no deaths or anaphylactic events requiring intramuscular epinephrine.This study demonstrates efficacy and safety of HDM sublingual tablets in pediatric patients with perennial allergic rhinitis due to HDM allergy. Treatment conferred significant and sustained improvement in symptom scores, with a similar immunologic response and safety profile, as previously shown in older age groups.This study is limited by a lack of objective outcomes, such as peak nasal inspiratory flow or nasal provocation tests. The investigators also excluded patients with persistent asthma and symptomatic rhinitis due to other allergens, which commonly occur in patients with HDM-triggered rhinitis. Although modest improvement in symptoms was shown, daily therapy over a 52-week treatment course may be impractical for pediatric patients. One likely goal of HDM immunotherapy may be to decrease use of other medications, but this was not seen in the current study. Further studies are needed in this population to assess optimal treatment duration and whether treatment confers sustained benefit after drug discontinuation.

Efficacy of house dust mite sublingual tablet in the treatment of allergic rhinoconjunctivitis: A randomized trial in a pediatric population.

BackgroundThe efficacy and safety of 300 index of reactivity (IR) tablets of house dust mite (HDM) allergen extracts in Japanese pediatric (5‐16 years old) patients with allergic rhinitis (AR) were assessed in a double‐blind, randomized, placebo‐controlled study (JAPIC CTI‐152981).MethodsPatients were randomized 1:1 to HDM sublingual tablets or placebo once daily for 52 weeks. The primary end‐point was average adjusted symptom score (AASS; average of daily Rhinitis Total Symptom Scores, comprising sneezing, rhinorrhea, nasal congestion, and nasal pruritus, adjusted for rescue medication use), analyzed during Weeks 48‐52 (mixed‐effects model for repeated measures).ResultsOf 438 patients randomized, 403 (92%; 193 active, 210 placebo) completed the study. AASS (least‐squares [LS] mean [SE]) during Weeks 48‐52 was significantly (P = 0.0005) lower in the active group compared with placebo (6.32 [0.20] vs 7.27 [0.19]; relative LS mean difference, −13%). Immunological responses (IgE and IgG4 antibodies specific to antigens of two HDM species) were significantly greater in the active group compared with placebo (P < 0.0001). Almost all patients experienced mild or moderate adverse events (AEs). The most common treatment‐related AEs were oral pruritus, mouth edema, throat irritation, and ear pruritus. One patient experienced serious pseudocroup (subglottic laryngitis) that recovered. There were no deaths or anaphylaxis requiring the use of injectable adrenaline.ConclusionsThe HDM tablet significantly improved symptoms of HDM‐induced perennial AR and was associated with a significant immunological response. The safety profile in pediatric patients was consistent with that in adults, with no new safety concerns.

Immunological Markers In House Dust Mite Allergic Subjects Treated With 300IR House Dust Mite Sublingual Tablets: Results From Two Phase III Trials

Immunological Markers In House Dust Mite Allergic Subjects Treated With 300IR House Dust Mite Sublingual Tablets: Results From Two Phase III Trials

P105 House dust mite sublingual tablets: efficacy and safety results from two phase III trials

Here, we report efficacy and safety results with house dust mite (HDM) sublingual tablets* investigated in two DBPC Phase III trials, one in adults in Europe (Study 1), one in adults/adolescents in Japan (Study 2).

P108 House dust mite sublingual tablets: subject profile and exposure in clinical development program

The clinical program of house dust mite (HDM) tablets* is conducted for treatment of patients with HDM-associated allergic rhinitis (HDM-AR). Here we present the clinical profile of enrolled adults, adolescents and children.

Clinical benefits of treatment with SQ house dust mite sublingual tablet in house dust mite allergic rhinitis.

Treatment with SQ (standardised quality) house dust mite sublingual tablet for 1year resulted in a decreased probability of having an allergic rhinitis (AR) exacerbation day (from 11% [placebo] to 5% [SQ house dust mite sublingual tablet]) and an increased probability of having a mild AR day (from 16% [placebo] to 34% [SQ house dust mite sublingual tablet]).

Standardized quality house dust mite sublingual tablets (Acarizax®): a guide to their use as sublingual allergy immunotherapy in Europe

Standardized quality (SQ) house dust mite (HDM) allergen extract tablets (Acarizax®) are a valuable option for sublingual allergy immunotherapy (SLIT) in adults with confirmed HDM-induced allergic rhinitis or allergic asthma. In placebo-controlled natural-field and environmental exposure challenge chamber trials, Acarizax® reduced the symptoms of allergic rhinitis in adults with HDM-induced allergic rhinitis (± asthma) and reduced the risk of asthma exacerbations in adults with HDM-induced allergic asthma. A systemic antibody response to HDM allergens has been observed within 4 weeks of initiating SLIT with Acarizax®. Precautions should be followed to minimize the risk of systemic and local allergic reactions inherent to SLIT.

ASCIA‐P49: SAFETY OF 300IR SUBLINGUAL TABLET OF HOUSE DUST MITE ALLERGEN EXTRACTS IN ADOLESCENTS WITH HOUSE DUST MITE‐ASSOCIATED ALLERGIC RHINITIS

Safety of house dust mite (HDM) sublingual tablets for the treatment of HDM-associated allergic rhinitis (AR) has been assessed across the clinical program. Here we present pooled safety data in adolescents treated with the 300IR dose. Adolescents (12–17 years) with medically confirmed HDM-associated AR were randomized in two Phase II/III double-blind studies conducted in Europe and Japan to receive a 300IR HDM tablet or placebo once daily for one year. Adverse events (AEs) were monitored throughout the studies and analyzed descriptively. 345 adolescents (300IR=173, Placebo = 172) comprised the Safety Set including 150 (43%) subjects with intermittent asthma at enrollment. The most commonly reported AEs during active treatment in the adolescents were mild or moderate application-site reactions such as throat irritation (13.9%), oral pruritus (9.8%) or mouth edema (8.7%). They occurred during the first day of treatment in nearly 20% of subjects and within the first month in about 50% of them. None of the serious AEs reported in 11 subjects (300IR=5, Placebo = 6) were considered drug-related. 18 subjects [300IR=12 (6.9%) and Placebo = 6 (3.5%)] withdrew due to an AE, mainly as a result of application-site reactions (e.g., upper abdominal pain, tongue edema). There were no reports of anaphylaxis and no use of epinephrine. Percentages of adolescents reporting at least one AE during active treatment or those reporting adverse reactions (ADRs) were similar in subjects with or without asthma [with asthma: 77% (AEs) and 50% (ADRs); without asthma: 78% (AEs) and 56% (ADRs)]. In both asthmatic and non-asthmatic subjects, the most frequent adverse reactions were those reported at the application site and were of similar incidences. A favorable safety profile of 300IR HDM sublingual tablets was demonstrated in adolescents with HDM-induced allergic rhinitis associated or not with intermittent asthma.

House dust mite sublingual tablets (Actair®): a guide to their use as allergy immunotherapy for house dust mite-induced allergic rhinitis

House dust mite (HDM) allergen extract sublingual tablets (Actair®) are a valuable option to reduce allergy symptoms in patients with HDM-induced allergic rhinitis. Allergy immunotherapy (AIT) with 300 index of reactivity (IR) Actair® reduced the symptoms of allergic rhinitis in placebo-controlled natural-field and environmental exposure challenge chamber trials. Significant beneficial effects with 300 IR Actair® relative to placebo were shown as early as 2 months after the initiation of treatment, with efficacy being continuously maintained during the rest of the 1-year AIT period, as well as during a subsequent AIT-free year. Precautions should be followed to minimize the risk of systemic and local allergic reactions inherent to AIT.

Pharmacodynamic and pharmacokinetic evaluation of house dust mite sublingually administered immunotherapy tablet in the treatment of asthma

Introduction: Sublingual immunotherapy (SLIT) for house dust mite (HDM) allergy has an evidence of efficacy demonstrated by meta-analyses, but marked differences are reported between the various SLIT products. The standardized quality (SQ) HDM sublingual tablet containing Dermatophagoides pteronyssinus and Dermatophagoides farinae in a 1:1 ratio (MK-8237) is a qualitative advance for SLIT products.Areas covered: The rationale for developing the HDM tablets is discussed against the other available SLIT products, analyzing the clinical data on efficacy and safety obtained by controlled trials.Expert opinion: Following preliminary Phase I and II studies, a double-blind, placebo-controlled trial on 604 patients with mite-induced asthma, aged more than 14 years and treated by inhaled budesonide, was performed using one of three active doses (1, 3 or 6 SQ) or placebo. The results showed a significant mean difference between 6 SQ-HDM and placebo in the reduction in daily budesonide dose of 81 µg (p = 0.004), with relative mean and median reductions of 42 and 50% for 6 SQ-HDM and 15 and 25% for placebo, respectively. Safety was very good, with no report of anaphylactic reaction. These findings suggest a role to the HDM SLIT tablets in the treatment of patients with mite-induced asthma.

Safety of the 300 IR and 500 IR Doses of a House Dust Mite Allergen Extracts Sublingual Tablet in Adults with Allergic Rhinitis

U E S D A Y 868 Safety of the 300 IR and 500 IR Doses of a House Dust Mite Allergen Extracts Sublingual Tablet in Adults with Allergic Rhinitis H el ene Nguyen, PharmD, Michel Roux, MD, Josiane CognetSic e, PharmD, Robert K. Zeldin, MD; Stallergenes S.A., Antony, France. RATIONALE: The efficacy of two doses (300IR and 500IR) of house dust mite (HDM) sublingual tablets was demonstrated in a randomized, DBPC study in patients with HDM-associated allergic rhinitis. Here we present the safety of this treatment. METHODS: Adults (18-50 years) with medically confirmed HDMassociated allergic rhinitis for at least one year were randomized to receive 300IR or 500IR HDM tablet or placebo once daily for one year and were followed for the subsequent year. Adverse events (AE) were monitored throughout the study and analyzed descriptively. All patients who received at least one dose of the investigational product were included in the safety set. RESULTS: 509 patients (300IR5170, 500IR5169, Placebo5170) were randomized and received at least one dose. 88% (300IR), 83% (500IR) and 80% (Placebo) reported at least one AE on treatment (TEAE). The most common TEAEs reported in the active groups were mild or moderate application site reactions i.e., oral pruritus (25-30% of patients), throat irritation (21-24%) and mouth edema (12-17%), which mostly occurred within the first month of treatment. Nine participants experienced serious TEAEs of which 4 were considered drug-related: pharyngeal edema (300IR), eczema (300IR), moderate respiratory distress related to a sublingual edema (500IR), and urticaria (Placebo); all recovered. Fortytwo patients (300IR517, 500IR520, and Placebo55) withdrew from the study due to a TEAE, most commonly pharyngeal edema, dyspepsia, nausea and mouth edema. CONCLUSIONS: Treatment with HDM sublingual tablets at doses of 300IR and 500IR was associated with a favorable safety profile. There was no appreciable difference in tolerability between the tested doses.

Efficacy and safety of sublingual tablets of house dust mite allergen extracts in adults with allergic rhinitis

Preliminary studies have suggested the efficacy of sublingual tablets of house dust mite (HDM) extracts in adults with allergic rhinitis. We sought to assess the efficacy and safety of 2 doses of HDM sublingual tablets over 1 treatment year and the subsequent immunotherapy-free year. Adults with HDM-associated allergic rhinitis were randomized in a double-blind, placebo-controlled study to receive 500 index of reactivity (IR) tablets, 300IR tablets, or placebo administered once daily for 1 year and were followed for the subsequent year. The primary efficacy variable was the Average Adjusted Symptom Score over the year 1 primary period (ie, October 1 to December 31). Symptoms and rescue medication scores, onset of action, patient-reported outcomes, and safety were secondary variables. The same end points were evaluated during the immunotherapy-free year. The primary efficacy end point was analyzed by using analysis of covariance. Five hundred nine participants were randomized, and 427 continued in the immunotherapy-free year. Both the 500IR and 300IR HDM sublingual tablets significantly reduced mean Average Adjusted Symptom Scores compared with placebo by -20.2% (P = .0066) and -17.9% (P = .0150), respectively. Efficacy of both doses was maintained during the treatment-free follow-up phase. The onset of action was at 4 months. Participants' global evaluation of treatment success was significantly higher in the 500IR and 300IR groups compared with the placebo group (P = .0206 and P = .0001, respectively). Adverse events were generally application-site reactions. There were no reports of anaphylaxis. Twelve months of treatment with 500IR and 300IR sublingual tablets of HDM allergen extracts was efficacious and well tolerated. Efficacy was maintained during the treatment-free follow-up year.