Efficacy and safety of sublingual tablets of house dust mite allergen extracts: Results of a dose-ranging study in an environmental exposure chamber

Roux, Michel J.; Devillier, Philippe; Yang, William H.; Montagut, A.; Abiteboul, Kathy; Viatte, Auguste; Zeldin, Robert K.

doi:10.1016/j.jaci.2016.03.039

Cited by 60 publications

(48 citation statements)

References 21 publications

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“…The drug substance HDM allergen content can be used as a representative measure of product strength for SLIT tablets of identical formulations and identical extract compositions, but it cannot be used to compare the actual, effective strengths of SLIT tablets that differ with regard to allergen composition, disintegration, and dissolution properties. This is supported by the finding that, while MTC (6 SQ-HDM/10,000 JAU) and ACZX (12 SQ-HDM/20,000 JAU) have shown consistent clinical effects [3,5,7], 100 IR/19,000 JAU ACT failed to meet statistically significant clinical endpoints in a phase 2 dose-finding trial [28], despite the higher or near-equal nominal strength (in JAU) and Der 1 content compared to MTC and ACZX, respectively. This strongly indicates that additional properties other than allergen content influence the clinical efficacy of SLIT tablets.…”

Section: Discussionmentioning

confidence: 85%

“…The optimal allergen dose must always be determined in clinical trials, as each AIT product has unique properties such as allergen content (dose and composition), formulation, and treatment regimen [27]. Clinically efficacious and non-efficacious doses were identified for 2 different HDM SLIT tablets in phase 2 HDM SLIT tablet dose-finding trials [8,28,29], and the clinical efficacy of the selected treatment doses on HDM-induced AR were later confirmed for both products in large phase 3 trials [3,5,6]. The freeze-dried SQ HDM SLIT tablet also reduced the risk of moderate or severe asthma exacerbations compared to placebo in a phase 3 trial in HDM allergic asthma [7].…”

Section: Discussionmentioning

confidence: 99%

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Bioavailability of House Dust Mite Allergens in Sublingual Allergy Tablets Is Highly Dependent on the Formulation

Ohashi-Doi¹,

Kito²,

Du³

et al. 2017

Int Arch Allergy Immunol

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Background: In sublingual immunotherapy (SLIT), the immune system is addressed by solubilized allergen that interacts with immunocompetent cells of the oral mucosa, the efficiency of which is governed by 2 main factors of SLIT allergen bioavailability: the allergen concentration and the mucosal contact time. Recently, 3 house dust mite (HDM) SLIT tablets were developed that differ with regard to allergen content, nominal strength (maintenance doses: 6 SQ-HDM/10,000 Japanese Allergen Units [JAU], 12 SQ-HDM/ 20,000 JAU, and 300 IR/57,000 JAU), and formulation (freeze-dried/compressed). Here, the importance of the SLIT tablet formulation for HDM major allergen bioavailability is examined. Methods: The HDM major allergen content, tablet disintegration times, and allergen release kinetics were determined. Dissolution kinetics (allergen concentration vs. time) of Der f 1, Der p 1, and Der 2 were measured. Area under the curve (AUC) was used as a surrogate parameter for allergen bioavailability. Results: The release of HDM major allergens from the freeze-dried tablets was complete after 30 s, while only partial release was achieved with the compressed tablets, even after prolonged dissolution. At 1 min, i.e., the recommended sublingual holding time for the freeze-dried tablets, the allergen bioavailability (AUC) of the compressed 300 IR/57,000 JAU tablet was 4.7-fold (Der f 1), 10.8-fold (Der p 1), and 23.6-fold (Der 2) lower than that of the freeze-dried 12 SQ-HDM/20,000 JAU tablet and similar to (Der f 1) and 5.3-fold (Der p 1) and 12.5-fold (Der 2) lower than that of the freeze-dried 6 SQ-HDM/10,000 JAU tablet. Conclusions: SLIT tablet allergen bioavailability depends highly on the tablet formulation. Only the fast-dissolving freeze-dried tablets provide maximal delivery of soluble allergens and achieve allergen concentrations that reflect the nominal tablet strengths within the recommended sublingual holding time.

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Section: Discussionmentioning

confidence: 85%

Section: Discussionmentioning

confidence: 99%

Bioavailability of House Dust Mite Allergens in Sublingual Allergy Tablets Is Highly Dependent on the Formulation

Ohashi-Doi¹,

Kito²,

Du³

et al. 2017

Int Arch Allergy Immunol

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“…Although the 2 HDM extracts have demonstrated their efficacy and safety in several studies, the extracts were usually compared with placebo or even self‐control group . In addition, the designs and predefined clinical outcomes varies greatly in different trials, which make the comparison of clinical benefits of different commercial HDM extracts become quite difficult . Until now, there have been very few head‐to‐head studies for HDM immunotherapy in AR patients.…”

Section: Discussionmentioning

confidence: 99%

The efficacy and safety of two commercial house dust mite extracts for allergic rhinitis: a head‐to‐head study

Yang

et al. 2019

Int Forum Allergy Rhinol

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Background: Several studies have demonstrated the efficacy of house dust mite (HDM) immunotherapy in allergic rhinitis (AR). We aimed to compare the efficacy and safety of 2 commercial HDM extracts in a Chinese AR population. Methods:This was an open-label study. HDM-associated AR patients were randomized into Dermatophagoides pteronyssinus (Dp) extracts (Alutard SQ; ALK, Hørsholm, Denmark) and Dp/Dermatophagoides farinae (Df) extracts (NovoHelisen Depot [NHD]; Allergopharma, Reinbek, Germany) groups. All patients received subcutaneous injections for 1 year, and were followed every 3 months during that 1-year period. Symptom score, medication score, and adverse reactions were recorded. The primary endpoint was the total combined symptom and medication score (CSMS) during the efficacy evaluation period. Blood samples were taken for specific immunoglobulin E (IgE), IgG4, and IgE-blocking factor tests at baseline and a er the 1-year treatment.Results: A total of 230 AR patients were randomized; 29 patients dropped out. Analysis of the primary endpoint demonstrated significant reductions in CSMS of 1.8 vs 3.1 (p < 0.001) in the Alutard group and 1.8 vs 3.3 (p < 0.001) in the NHD group compared with baseline. The 2 groups presented equal effectiveness with regard to CSMS, symptom score, and medication score (p > 0.05). The treatment was well tolerated in both groups; 17 (14.8%) patients experienced systemic reactions (SRs) in the Alutard group and 13 (11.3%) in the NHD group. The rates of SRs showed no difference in the 2 groups (p > 0.05), and no anaphylaxis occurred. IgG4 and IgE-blocking factor to Dp and Df were increased significantly in both groups a er the 1-year treatment. Conclusion:Our study confirmed the equal efficacy and safety profile of both commercial extracts in HDMassociated AR patients. C 2019 ARS-AAOA, LLC. et al. The efficacy and safety of two commercial house dust mite extracts for allergic rhinitis: a head-to-head study. Int Forum Allergy Rhinol. 2019;9:876-882.

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“…Indeed, the efficacy of dust mite SLIT in reducing rhinitis symptoms was recently established in an environmental exposure chamber study. 176 As an extension of this concept, in a randomized trial of asthmatic patients with dust mite allergy whose symptoms were poorly controlled with inhaled corticosteroids, the addition of SLIT to maintenance medications modified the occurrence of asthma exacerbations during a period when inhaled corticosteroids were reduced. 177 …”

Section: Future Directions and Clinical Implicationsmentioning

confidence: 99%

Pathogenic CD4 + T cells in patients with asthma

Muehling

Lawrence

Woodfolk

2017

Journal of Allergy and Clinical Immunology

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Asthma encompasses a variety of clinical phenotypes that involve distinct T cell–driven inflammatory processes. Improved understanding of human T-cell biology and the influence of innate cytokines on T-cell responses at the epithelial barrier has led to new asthma paradigms. This review captures recent knowledge on pathogenic CD4+ T cells in asthmatic patients by drawing on observations in mouse models and human disease. In patients with allergic asthma, TH2 cells promote IgE-mediated sensitization, airway hyperreactivity, and eosinophilia. Here we discuss recent discoveries in the myriad molecular pathways that govern the induction of TH2 differentiation and the critical role of GATA-3 in this process. We elaborate on how cross-talk between epithelial cells, dendritic cells, and innate lymphoid cells translates to T-cell outcomes, with an emphasis on the actions of thymic stromal lymphopoietin, IL-25, and IL-33 at the epithelial barrier. New concepts on how T-cell skewing and epitope specificity are shaped by multiple environmental cues integrated by dendritic cell “hubs” are discussed. We also describe advances in understanding the origins of atypical TH2 cells in asthmatic patients, the role of TH1 cells and other non-TH2 types in asthmatic patients, and the features of T-cell pathogenicity at the single-cell level. Progress in technologies that enable highly multiplexed profiling of markers within a single cell promise to overcome barriers to T-cell discovery in human asthmatic patients that could transform our understanding of disease. These developments, along with novel T cell–based therapies, position us to expand the assortment of molecular targets that could facilitate personalized treatments.

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Efficacy and safety of sublingual tablets of house dust mite allergen extracts: Results of a dose-ranging study in an environmental exposure chamber

Abstract: A dose-dependent effect of sublingual HDM immunotherapy was demonstrated in this environmental exposure chamber study, supporting further development of this treatment.

Cited by 60 publications

References 21 publications

Bioavailability of House Dust Mite Allergens in Sublingual Allergy Tablets Is Highly Dependent on the Formulation

Bioavailability of House Dust Mite Allergens in Sublingual Allergy Tablets Is Highly Dependent on the Formulation

The efficacy and safety of two commercial house dust mite extracts for allergic rhinitis: a head‐to‐head study

Pathogenic CD4 + T cells in patients with asthma

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