A milestone in house dust-mite-allergen immunotherapy: the new sublingual tablet S-524101 (actair)

Abstract

Subcutaneous allergen-specific immunotherapy has long been used in the treatment of allergic rhinitis and/or asthma and its efficacy has been confirmed. However, due to the discomfort of injections and the risk of severe adverse reactions, alternative routes of allergen administration have emerged. Delivery of allergens through the mucosal route had been proposed and investigated thoroughly, confirming the sublingual route to be the most efficacious. Later, the efficacy and safety of this route have been documented by numerous controlled trials both for house dust mite (HDM) and pollens. Recently, sublingual orodispersable grass pollen allergen tablets were in use followed by the newly developed HDM allergen tablets with satisfactory clinical results: Moreover, very recently 1 year of HDM tablet treatment was demonstrated to exert its clinical efficacy 1 year after discontinuation of tablet IT. The persistence of efficacy after only 1 year of treatment is a new and promising era. Currently, Sublingual Immunotherapy is the most easily administered and safe treatment option until more immunogenic, less allergenic and more efficient allergen extracts are developed.

Keywords::

• allergic rhinitis
• asthma
• house dust mite
• orodispersible tablets
• sublingual

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• The oral mucosa is efficient in immunological processes leading to a reduction of allergic symptoms during SLIT due to the presence of oral Langerhans cells located within the suprabasal epithelia. Oral Langerhans’ cells highly express FcεRI on their surface which captures the allergen during SLIT, then matures and migrates to proximal draining lymph nodes for tolerance induction.

• SLIT induces; allergen-specific IgG production in a dose-dependent manner and blunts allergen-specific IgE responses, allergen-induced CD4+CD25+Foxp3+ T regulatory cells and their production of TGF-β and IL-10, Foxp3 expression of sublingual T cells and serum inhibitory activity for IgE facilitated binding.

• House dust mites (HDMs) are one of the major aeroallergens worldwide and nearly 85% of patients with asthma are sensitized to HDM. Sensitization to HDM is a risk factor for development of asthma in children.

• Efficacy and safety of HDM SLIT drops have been proven and being used widely for a few decades all over Europe, development of HDM oro-dispersable sublingual tablets, is one of the most important contributions to the cure of allergic diseases, due to its stability on room temperature when compared to liquid formulations.

• Recombinant HDM allergen tablets are expected to strengthen the efficacy and immunogenity, and reduce allergenity and duration of treatment of allergen vaccines.