Long-lasting effects of sublingual immunotherapy according to its duration: A 15-year prospective study

Pneumology Unit, Cuasso al Monte, Macchi Hospital Foundation, Varese, Italy.
The Journal of allergy and clinical immunology (Impact Factor: 11.48). 10/2010; 126(5):969-75. DOI: 10.1016/j.jaci.2010.08.030
Source: PubMed


Data on the long-term effects of sublingual immunotherapy (SLIT) are sparse, and the optimal duration of treatment is a matter of debate.
We sought to prospectively evaluate the long-term effect of SLIT given for 3, 4, or 5 years and to compare the effect of those different durations.
In this prospective open controlled study we followed up patients with respiratory allergy who were monosensitized to mites for 15 years. The subjects were divided in 4 groups receiving drug therapy alone or SLIT for 3, 4, or 5 years. Clinical scores, skin sensitizations, methacholine reactivity, and nasal eosinophil counts were evaluated every year during the winter months. The clinical effect was considered to persist until clinical scores remained at less than 50% of the baseline value, and then patients underwent another course of SLIT.
Seventy-eight patients were enrolled, and 59 completed the study. In the 12 control subjects no relevant change in clinical scores was seen throughout the study. In the patients receiving SLIT for 3 years, the clinical benefit persisted for 7 years. In those receiving immunotherapy for 4 or 5 years, the clinical benefit persisted for 8 years. New sensitizations occurred in all the control subjects over 15 years and in less than a quarter of the patients receiving SLIT (21%, 12%, and 11%, respectively). The second course of vaccination induced a benefit more rapidly than the first course. The behavior of bronchial hyperreactivity and nasal eosinophils paralleled the clinical score.
Under the present conditions, it can be suggested that a 4-year duration of SLIT is the optimal choice because it induces a long-lasting clinical improvement similar to that seen with a 5-year course and greater than that of a 3-year vaccination.

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Available from: Maurizio Marogna, Feb 22, 2015
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    • "Na podstawie dostępnych badań można przyjąć, że największą skutecznością cechują się szczepionki zawierające alergeny pyłku traw i brzozy [9] [54]. Szczególnie istotny jest długotrwały efekt kliniczny utrzymujący się po zaprzestaniu SLIT, który wykazano u pacjentów leczonych z powodu uczulenia na pyłek traw oraz roztocze kurzu domowego [50] [55]. Szczególnie ważnym zagadnieniem jest skuteczność SLIT w grupie pacjentów pediatrycznych. "
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    ABSTRACT: SLIT (sublingual immunotherapy) is a therapeutic method aiming at producing allergen-specific tolerance of the immune system to a gradually increasing dose of an allergen that is administered sublingually. SLIT initiates similar immune mechanisms as does subcutaneous immunotherapy (SCIT). The aim of the study at this position is to update the current knowledge on sublingual immunotherapy. Randomized double-blind, placebo-controlled (RDBPC) studies that compared both immunotherapy forms point to an advantage of SCIT over SLIT in decreasing symptoms of asthma and allergic rhinitis, a comparable effect of both the methods on immune parameters (sIgE, IL-10) and upper respiratory tract inflammations and an advantage of SCIT over SLIT with respect to lower respiratory tract inflammations as based on provocation tests. At present, there are no grounds for recommending SLIT in food allergy. In view of the high safety profile and absence of anxiety-provoking infections, SLIT may be the method that is more often selected in children as compared to adults. On the other hand, immune mechanisms and results of clinical trials provide an argument for preferential employment of SCIT in adults. It should be borne in mind, however, that SLIT is effective if a good quality vaccine with a high allergen dose, is employed for at least three years. National and international reports indicate the necessity of conducting further clinical trials, especially including a direct comparison between SCIT and SLIT with respect to effectiveness and safety.
    01/2014; 1(1):30–37. DOI:10.1016/j.alergo.2014.03.002
    • "In a further study, the same authors prospectively evaluated the long-term effect of SLIT given for 3, 4, or 5 years on 78 patients, 59 of whom completed the study, compared with 12 control subjects. The total duration of the follow-up was 15 years [27]. According to new sensitizations, all the control subjects over the 15 years period developed positive test to allergens previously negative, while this occurred in less than a quarter of the patients receiving SLIT (21% in treated for 3 years, 12%, in treated for 4 years, and 11% in treated for 5 years, respectively). "
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    ABSTRACT: Allergen immunotherapy (AIT) is the practice of administering gradually increasing doses of the specific causative allergen to reduce the clinical reactivity of allergic subjects. A bulk of literature demonstrates that AIT is an effective and safe treatment to reduce allergic symptoms and the use of drugs. The preventive capacity of AIT is less investigated. The studies thus far available showed that this treatment, in both forms of subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) is able to prevent the development of asthma in patients with allergic rhinitis and the occurrence of new sensitizations in patients monosensitized. Such outcomes demonstrate the ability of AIT to change the natural history of respiratory allergy. Of particular importance, SCIT with Hymenoptera venom has an invaluable role in preventing potentially fatal anaphylactic reactions to the culprit sting in venom-allergic patients. Ongoing studies are aimed at evaluating the possible capacity of AIT in primary prevention of allergy. All these capabilities are related to the mechanisms of action of AIT. In fact, both SCIT and SLIT are able to modify the allergen presentation by dendritic cells that in turn modify the phenotype of allergen-specific T cells, switching from the Th2-type response, typical of allergic inflammation, to a Th1-type response. An important role is played by allergen-specific T regulatory (Treg) cells, which produce suppressive cytokines such as IL-10 and TGF-beta.
    Journal of preventive medicine and hygiene 06/2013; 54(2):71-4.
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    • "Another large-scale study has also documented the clinical efficacy of SLIT in perennial allergy (i.e., to house dust mites) using a tablet containing extracts from the two common D. pteronyssinus and D. farinae mite species [30]. Other trials have demonstrated a long-term efficacy of sublingual immunotherapy, for example, following a three-year administration of grass pollen tablets [31] [32]. In addition, those allergic patients remained protected for at least two years after stopping the treatment, thus documenting a " disease-modifying " effect of SLIT. "
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    ABSTRACT: The clinical efficacy of sublingual immunotherapy (SLIT) with natural allergen extracts has been established in IgE-dependent respiratory allergies to grass or tree pollens, as well as house dust mites. Sublingual vaccines have an excellent safety record, documented with approximately 2 billion doses administered, as of today, in humans. The oral immune system comprises various antigen-presenting cells, including Langerhans cells, as well as myeloid and plasmacytoid dendritic cells (DCs) with a distinct localisation in the mucosa, along the lamina propria and in subepithelial tissues, respectively. In the absence of danger signals, all these DC subsets are tolerogenic in that they support the differentiation of Th1- and IL10-producing regulatory CD4(+) T cells. Oral tissues contain limited numbers of mast cells and eosinophils, mostly located in submucosal areas, thereby explaining the good safety profile of SLIT. Resident oral Th1, Th2, and Th17 CD4(+) T cells are located along the lamina propria, likely representing a defence mechanism against infectious pathogens. Second-generation sublingual vaccines are being developed, based upon recombinant allergens expressed in a native conformation, possibly formulated with Th1/T reg adjuvants and/or mucoadhesive particulate vector systems specifically designed to target oral dendritic cells.
    Clinical and Developmental Immunology 01/2012; 2012(1740-2522):623474. DOI:10.1155/2012/623474 · 2.93 Impact Factor
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