The global development and clinical efficacy of sublingual tablet immunotherapy for allergic diseases

Abstract

Allergy immunotherapy (AIT) is a treatment option for respiratory allergy that is complementary to pharmacotherapy, with a distinct mechanism of action. Alternative methods to subcutaneous administration of AIT that enable patients to safely self-administer AIT is considered an unmet clinical need. The sublingual immunotherapy tablet (SLIT-tablet) is an orally disintegrating pharmaceutical formulation (oral lyophilisate) containing standardized allergens. SLIT-tablets have been developed for sublingual immunotherapy (SLIT) of cedar-pollen, grass-pollen, ragweed-pollen, tree-pollen, and house dust mite allergies. It is a once-daily tablet treatment to be self-administered after the first dose has been provided under the supervision of a physician with experience in the diagnosis and treatment of allergic diseases. Once the first dose is adequately tolerated, subsequent doses may be self-administered. SLIT-tablets have proven efficacy for allergic rhinitis (AR) with and without conjunctivitis (C) and allergic asthma (AA) in adults, children, and poly-sensitized allergic patients. Meta-analyses indicate that SLIT-tablets have superior or similar efficacy compared with anti-allergic pharmacotherapies for seasonal AR and superior efficacy for perennial AR. SLIT-tablets have also demonstrated clinically relevant improvements of asthma, with significant reductions in the following: daily inhaled corticosteroid use, risk of asthma exacerbations, and asthma symptoms. SLIT-tablets are generally well tolerated, with a low risk of systemic allergic reactions. The most common treatment-related adverse events are mild-moderate oral reactions. Current evidence supports SLIT-tablets to be considered as an alternative or add-on treatment to pharmacotherapy for AR/C and asthma. Future SLIT developments may include early intervention to prevent the development or progression of allergic disease in children.

Allergen Immunotherapy in Children User’s Guide

“…For regulatory reasons, clinical trials on pediatric patients are performed after first evidence in adults; thus, the evidence arising from pediatric trials is lower. However, combined experience performed on the trials for grass sublingual tablet registration both in adults and in children supports similar clinical effect and underlying mechanisms …”

Impact on quality of life and safety of sublingual and subcutaneous immunotherapy in children with severe house dust mite and pollen-associated allergic rhinoconjunctivitis

“…13 (11)(12)(13)(14) 15 (14)(15)(16) < 0.001 11 (10)(11)(12)(13)(14)(15) 12 (9)(10)(11)(12)(13)(14)(15)(16) 0.5…”

Diverse Mechanisms of Allergen Specific Immunotherapy

“…Different formulations of allergens have been developed as alternatives to SCIT, such as the sublingual immunotherapy tablet (SLIT-tablet). Particularly SLIT-tablets may be beneficial for children who are scared of injections and needles [14]. The SLIT-tablets have been developed for the treatment of grass pollen-induced AR and HDMinduced AR but the allergen content and dosing have not been standardized to date.…”

“…The varied content among different products also affects the guidelines [15]. In addition, a limitation of SLIT tablet occurs from its ingredient which consists of only one antigen [14]. It has been recently demonstrated that pharmaceutical SLIT-tablet formulations are also important and affects the efficacy with which allergen has delivered from the dry state of the tablet into a soluble form [16].…”

“…It has been recently demonstrated that pharmaceutical SLIT-tablet formulations are also important and affects the efficacy with which allergen has delivered from the dry state of the tablet into a soluble form [16]. SLIT has a good safety and tolerability profile compared to SCIT owing to the lack of systemic exposure to intact allergens and low frequency of systemic allergic reactions [14].…”