Standardized quality (SQ) house dust mite sublingual immunotherapy tablet (ALK) reduces inhaled corticosteroid use while maintaining asthma control: A randomized, double-blind, placebo-controlled trial

doi:10.1016/j.jaci.2014.03.019

Journal of Allergy and Clinical Immunology

Volume 134, Issue 3, September 2014, Pages 568-575.e7

https://doi.org/10.1016/j.jaci.2014.03.019 Get rights and content

Background

Investigations meeting current standards are limited for the effect of house dust mite (HDM) allergy immunotherapy in asthmatic patients.

Objective

This trial investigated the efficacy and safety of a standardized quality (SQ; allergen standardization method proprietary to the trial sponsor) HDM SLIT-tablet (ALK, Hørsholm, Denmark) in adults and adolescents with HDM respiratory allergic disease. This publication reports the results of the endpoints related to asthma.

Methods

Six hundred four subjects 14 years or older with HDM allergic rhinitis and mild-to-moderate asthma were randomized 1:1:1:1 to double-blind daily treatment with one of 3 active doses (1, 3, or 6 SQ-HDM) or placebo. Their use of inhaled corticosteroid (ICS) was standardized and adjusted at baseline and the end of treatment to the lowest dose providing asthma control. The primary end point was a reduction in ICS dose from the individual subject's baseline dose after 1 year of treatment.

Results

The primary analysis revealed a mean difference between 6 SQ-HDM and placebo in the reduction in daily ICS dose of 81 μg (P = .004). Relative mean and median reductions were 42% and 50% for 6 SQ-HDM and 15% and 25% for placebo, respectively. No statistically significant differences were observed for the other assessed asthma parameters, reflecting the intended controlled status of the trial subjects. The most common adverse events were local reactions in the mouth. The rate and severity of adverse events were higher for 3 and 6 SQ-HDM than for 1 SQ-HDM and placebo.

Conclusion

Efficacy in mild-to-moderate asthma of 6 SQ-HDM relative to placebo was demonstrated by a moderate statistically significant reduction in the ICS dose required to maintain asthma control. All active doses were well tolerated.

Section snippets

Ethics

The trial is identified by EudraCT number 2006-001795-20 and ClinicalTrials.gov Identifier NCT00389363. The trial was designed, approved, consented to, and conducted according to the principles of ICH Good Clinical Practice.¹⁷

Intervention medication

The tablets (active and placebo) were manufactured and provided by the sponsor and were oral lyophilisates, either containing standardized extracts of Dermatophagoides pteronyssinus and Dermatophagoides farinae in a 1:1 ratio or a placebo that was similar in appearance,

Trial population

Subject disposition is summarized in Table I. The full analysis set (FAS) comprised 604 randomized subjects. Eighty-eight percent completed the trial, evenly distributed over treatment groups. The rate of AE discontinuations was numerically slightly higher for 3 SQ-HDM than for the other treatment groups.

Demographic and selected baseline characteristics are summarized in Fig 2. All parameters were generally similar between treatment groups, and baseline body characteristics were within the

Discussion

The trial was double-blinded, and no indications of generally compromised blinding were present during the trial. It has previously been discussed whether the occurrence of local side effects with SLIT-tablets could potentially compromise blinding.³⁵ An analysis of data pooled from 4 clinical trials investigating the effect of an SQ grass SLIT-tablet in patients with allergic rhinoconjunctivitis has been conducted. The data were pooled to ensure sufficient power of the subgroup analyses, and

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Long-term efficacy of house dust mite sublingual immunotherapy on clinical and pulmonary function in patients with asthma and allergic rhinitis
2024, Journal of Allergy and Clinical Immunology: Global
A previous study reported that house dust mite (HDM) sublingual immunotherapy (SLIT) for 48 weeks was effective as add-on treatment for allergic asthma; however, data regarding its long-term efficacy are scarce.
We sought to evaluate the effect of HDM SLIT on asthma control, pulmonary function, and airway inflammation and remodeling throughout the 5-year treatment period.
A total of 140 patients with asthma and allergic rhinitis sensitized to HDM were randomized to receive either drugs alone or drugs plus SLIT for 5 years. The 5-item Asthma Control Questionnaire (ACQ-5), Asthma Quality of Life Questionnaire (AQLQ), Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), spirometry, quantitative computed tomography, and type 2 biomarkers were assessed.
An improvement in the ACQ-5, AQLQ, and RQLQ scores was observed in the SLIT group compared with the control group. HDM SLIT increased lung function and reduced the percentage of airway wall area. The levels of fractional exhaled nitric oxide (Feno), blood eosinophil, serum specific IgE for HDM, and total IgE decreased and were sustained during the 5 years. The change in type 2 biomarkers correlated with change in the AQLQ score. On the basis of receiver-operating characteristic analysis for predicting responders, the area under the receiver-operating characteristic curve in FEV₁% predicted, airway wall area, Feno, and specific IgE was high. Multivariate regression analysis showed that the strongest predictor of responders was Feno.
HDM SLIT continued to provide sustained efficacy, improve lung function, and prevent progression of airway inflammation and remodeling in asthma throughout the 5-year treatment period.
Short-term and long-term efficacy of sublingual immunotherapy in different courses for house dust mite-induced allergic rhinitis
2024, American Journal of Otolaryngology - Head and Neck Medicine and Surgery
Sublingual immunotherapy (SLIT) has been proven to be an effective and safe treatment for patients with house dust mite (HDM)-induced allergic rhinitis (AR) to achieve short-term and long-term efficacy. This study aimed to investigate the relationship between SLIT duration and long-term efficacy.
This study involved 134 patients who underwent SLIT between 2019 and 2021 (in the 2-year group), between 2018 and 2021(in the 3-year group), or between 2017 and 2021 (in the 4-year group). The total nasal symptoms score (TNSS), total medication score (TMS), visual analogue scale (VAS), the Mini Rhinoconjunctivitis Quality of Life Questionnaire (MiniRQLQ) and adverse events (AEs) were assessed at baseline, after treatment (2021) and one year after the treatment completion (2022). The correlation between MiniRQLQ and other indicators was also analyzed.
After SLIT, patients in all three groups showed significant improvements in TNSS, TMS, VAS and MiniRQLQ scores (all p < 0.001). These improvements were sustained even one year after SLIT. Patients who received 3–4 years of SLIT showed significant improvement compared with those who received 2 years of SLIT in all clinical outcomes (all p < 0.01). The analysis showed positive correlations between the MiniRQLQ and TNSS, TMS, and VAS (all p < 0.001). No significant difference was observed in the AE rate in all three groups (p > 0.05).
Different duration of HDM SLIT could generate various short-term and long-term clinical efficacy. The MiniRQLQ could be applied to evaluate SLIT efficacy in clinical practice.
Allergen Immunotherapy for Asthma
2024, Journal of Allergy and Clinical Immunology: In Practice
Allergen immunotherapy is a disease-modifying treatment for IgE-mediated allergies reducing disease burden and symptoms in patients with allergic rhinitis, with or without asthma. The growing evidence that allergen immunotherapy also has the potential to facilitate achieving asthma control in patients with allergic asthma resulted in its acknowledgment by international bodies (Global Initiative for Asthma and European Academy of Allergy and Clinical Immunology) as add-on treatment for mild/moderate asthma. Although there have been promising developments in biomarkers for patient selection and for allergen immunotherapy efficacy evaluation in patients with asthma, a lot more data are still required.
Prevention Is Better than Cure: Impact of Allergen Immunotherapy on the Progression of Airway Disease
2024, Journal of Allergy and Clinical Immunology: In Practice
Allergen immunotherapy is highly effective for seasonal pollinosis. Three years of treatment results in long-term efficacy. This disease modification is accompanied by downregulation of allergen-specific Th2 responses and the induction of persistent specific IgG- and IgA-associated IgE-blocking activity. In children with seasonal rhinitis, both subcutaneous and sublingual pollen immunotherapy have been shown to reduce the development of asthma symptoms and asthma medication requirements. House dust mite tablet allergen immunotherapy has been shown to be effective for perennial mite–driven rhinitis in adults and children and may suppress asthma exacerbations, whereas its long-term efficacy has yet to be explored. The success of primary prevention of peanut allergy in childhood by introduction of peanut into the diet during infancy provides a strong rationale to explore whether primary prevention of inhalant allergies and asthma may also be possible. House dust mite allergy is a major risk factor for developing asthma. Preliminary data in at-risk children suggest that sublingual house dust mite immunotherapy initiated during infancy could reduce the onset of multiple allergen sensitizations and prevent the development of asthma at age 6 years. This possibility should now be explored in an adequately powered, prospectively randomized controlled trial.
Advancing precision medicine in asthma: Evolution of treatment outcomes
2023, Journal of Allergy and Clinical Immunology
The article discusses the historical evolution of asthma treatment and highlights recent advancements in personalized medicine, specifically the use of biologics in severe asthma therapy and its potential combination with allergen immunotherapy (AIT). One of the major breakthroughs of biologics is their potential effect on airway remodeling, a crucial aspect of asthma chronicity. The article introduces the concept of disease-modifying antiasthmatic drugs, which aim to modify the course of asthma and possibly modulate or prevent airway remodeling. Furthermore, the critical importance of patient-centered outcome measures to evaluate the efficacy and effectiveness of asthma treatments is emphasized, with the innovative concept of asthma remission introduced as a potential outcome. Recent studies suggest that AIT can be used as an additional therapy to biologic agents for the treatment of allergic asthma. The combination of these treatments has been shown to induce improved clinical outcomes. However, AIT is actually not recommended for use in patients with severe asthma, but encouraging results from studies investigating the combined use of AIT and biologics indicate a novel approach to exploring these treatment modalities. In conclusion, the introduction of biologics and AIT has changed the scenario of respiratory allergy treatment, from a “one size fits all” approach to embracing “individual treatments.”
Allergen immunotherapy for allergic asthma: The future seems bright
2023, Respiratory Medicine
Allergen specific immunotherapy (AIT) is the only causal therapeutic option for allergic airway diseases including asthma and allergic rhinitis. AIT has been shown to restore the allergen immune tolerance, can modify both the early and late-onset allergen-specific airway hyperreactivity, helps to achieve disease control/remission and prevents new sensitisations. Recent real life data on long-term effectiveness of house dust mite (HDM) AIT in a large group of patients with HDM-driven asthma further underscored its unique therapeutic potential as well as confirmed previous data with pollen AIT. More widespread use of this causal treatment in select patient populations should further move this promising therapeutic field. In this mini-review, we discuss updates on new insights based on real world patient data.

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: Sponsored by ALK-Abelló, Hørsholm, Denmark, who assumes overall responsibility for the trial and has been involved in both trial design and conduct.

: Disclosure of potential conflict of interest: H. Mosbech has received consultancy fees for help in preparation of protocol, has received support for travel to European congresses and international allergologic and pulmonologic congresses, is an advisory board member, and has received lecture fees for postgraduate educational activities on allergologic topics from ALK-Abelló. F. de Blay has received research support, consultancy fees, travel support, and participation fees from ALK-Abelló; is a board member for and has received consultancy fees from Novartis, Boehringer, Stallergenes, and Meda Pharma; has received research support from AstraZeneca; and has received lecture fees from Novartis, Stallergenes, Meda Pharma, GlaxoSmithKline, and MSD. L. Prieto Andres is a board member for GlaxoSmithKline, Novartis, and Stallergenes and has received lecture fees from GlaxoSmithKline and Novartis. C. Ljørring is employed by and has stock/stock options in ALK-Abelló. G. W. Canonica has received research support from ALK-Abelló, Almirall, Allergy Therapeutics, Allergopharma, Anallergo, HAL, Lofarma, and Stallergenes. The rest of the authors declare that they have no relevant conflicts of interest.

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Asthma and lower airway diseaseStandardized quality (SQ) house dust mite sublingual immunotherapy tablet (ALK) reduces inhaled corticosteroid use while maintaining asthma control: A randomized, double-blind, placebo-controlled trial

Background

Objective

Methods

Results

Conclusion

Section snippets

Ethics

Intervention medication

Trial population

Discussion

J Allergy Clin Immunol

J Allergy Clin Immunol

WAO J

Respir Med

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

Prevalence and rate of diagnosis of allergic rhinitis in Europe

Eur Respir J

Global burden of asthma

Allergy

A population-based clinical study of allergic and non-allergic asthma

J Asthma

Sensitisation to airborne moulds and severity of asthma: cross sectional study from European Community respiratory health survey

BMJ

The link between allergic rhinitis and allergic asthma: a prospective population-based study. The Copenhagen Allergy Study

Allergy

WHO Position Paper. Allergen immunotherapy: Therapeutic vaccines for allergic diseases

Allergy

Allergic Rhinitis and its Impact on Asthma (ARIA) 2008 update (in collaboration with the World Health Organization, GA(2)LEN and AllerGen)

Allergy

Long-term clinical efficacy of grass-pollen immunotherapy

N Engl J Med

Specific immunotherapy has long-term preventive effect of seasonal and perennial asthma: 10-year follow-up on the PAT study

Allergy

SQ-standardized sublingual grass immunotherapy: confirmation of disease modification 2 years after 3 years of treatment in a randomized trial

J Allergy Clin Immunol

Asthma and lower airway disease
Standardized quality (SQ) house dust mite sublingual immunotherapy tablet (ALK) reduces inhaled corticosteroid use while maintaining asthma control: A randomized, double-blind, placebo-controlled trial