State of the Art: Development of a Sublingual Allergy Immunotherapy Tablet for Allergic Rhinitis in Japan

Abstract

Allergic rhinitis (AR) caused by house dust mite (HDM) and Japanese cedar pollen (JCP) represents a significant, expanding health problem in Japan. Allergic symptoms often have a severe impact on the QOL such as sleep disturbance and reduced school and work performance. In addition to the classical symptoms, AR is known to be a risk factor for the development of allergic asthma, a potentially life-threatening condition. Allergy immunotherapy (AIT) is a well-documented, safe, effective treatment option for respiratory allergic disease. It has been demonstrated that AIT can provide relief from clinical symptoms and that AIT has the potential to provide long-term post-treatment effect. Although the mechanism of AIT is not fully understood, it can actively modulate protective allergen-reactive pathways of the immune system and alter the natural course of disease. Unlike pharmacotherapy, AIT addresses the basic immunological mechanisms that are responsible for the development and persistence of allergic conditions. Currently two main routes of AIT administration are commonly available, subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT). Both SCIT and SLIT are clinically effective, and SLIT is particularly well tolerated, with a lower risk of systemic allergic reactions compared with SCIT. To date, SLIT tablets have been developed for a range of different allergies including HDM and JCP and are the best-documented AIT treatment form. Here we introduce the current status of development of a SLIT tablet in Japan for AR, examine the clinical aspects and mechanism of action of AIT, and discuss the future directions of SLIT.

Allergen Release Profiles of Fast-Dissolving Freeze-Dried Orodispersible Sublingual Allergy Immunotherapy Tablets

“…50 In AIT, where the more conventional regimens of repeated subcutaneous injections may be considered invasive and resource demanding for both children and parents/caregivers, fast-dissolving SLIT-tablets provide a treatment option with daily self-administration after the first dose has been taken under medical supervision. 10 , 11 , 18 , 20 …”

“… 6 , 7 , 8 Allergy is an immunologic disease and through repeated administration of extracts of the sensitizing allergen, the immune-modulatory effects of AIT lead to a series of events starting with rapid desensitization of effector cells (ie, mast cells and basophils) followed by production of protective allergen-specific antibodies (eg, immunoglobulin G 4 and immunoglobulin A) and suppression of allergen-specific effector T-cell subsets by regulatory B-cells and T-cells. 9 , 10 …”

Allergen-specific immunotherapy in allergic rhinitis

“…Существует по крайней мере пять способов введения аллергенов при АСИТ: подкожный [7-9], подъязычный [10][11][12], оральный [13][14][15], эпикутанный [16,17] и внутрилимфатический [18,19]. В настоящее время документировано и апробировано два пути введения аллергенов для применения в практике: подкожный [7] и подъязычный [10]. Третий путь, оральный, находится в разработке.…”

“…Таблетки и капли вводятся под язык и держатся до проглатывания или выплевываются. Потенциал подъязычной АСИТ обусловлен безопасностью и низким риском системных побочных реакций, достижением долгосрочного клинического эффекта и отсутствием необходимости частого посещения медицинского учреждения и консультирования у аллерголога [10,11]. Поэтому лечение может быстро претерпевать изменения в составе аллергенов, если это потребуется.…”

Next-Generation Allergen-Specific Immunotherapy for Japanese Cedar Pollinosis Using Molecular Approaches

“…SLIT with a new standardized JC pollen extract for JC pollinosis was approved in October 2014 by the Japanese Ministry of Health, Labour, and Welfare. 21 At present, SLIT for JC pollinosis is achieved by placing the allergen under the tongue via either SLIT drops (Cedartolen) in an aqueous formulation of allergen extract or SLIT tablets (CedarCure) in a freeze-dried formulation. JC-pollen SLIT drops (Cedartolen) have usually been used at a dose of 2,000 JAU (Japanese allergy unit) containing 1.5–4.2 µg Cry j 1 as the maximum concentration for the maintenance phase.…”