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Respiratory Allergy Editorial
Sublingual Immunotherapy for Respiratory Allergy
Moises A Calderon
Professor of Internal Medicine and Allergy, Imperial College London, National Heart and Lung Institute, Royal Brompton Hospital NHS, London, UK
Abstract Sublingual allergen immunotherapy (SLIT) is a new alternative for the treatment of respiratory allergy. Strong evidence-based medicine data
on clinical efficacy and safety about SLIT support the new standardised products register in Europe and the US. SLIT-tablets significantly
reduce nasal and ocular symptoms scores, reduce the use of relief medication and improves quality of life in both adults and children with
pollen respiratory allergy. New data support its efficacy and safety for house dust mites (HDM) respiratory allergy.
Keywords Sublingual immunotherapy, allergic rhinitis, allergic asthma, respiratory allergy
Disclosure: Moises A Calderon has received lecture fees from ALK, Allergopharma, Merck and Stallergenes and served as a consultant to ALK, Hal Allergy, Merck and
Stallergenes. No funding was received for the publication of this article.
Open Access: This article is published under the Creative Commons Attribution Noncommercial License, which permits any non-commercial use, distribution, adaptation
and reproduction provided the original author(s) and source are given appropriate credit.
Received: 23 June 2015 Published Online: 17 August 2015 Citation: European Respiratory and Pulmonary Diseases, 2015;1(1):25–6
Correspondence: Moises A Calderon, Imperial College London, National Heart and Lung Institute, Royal Brompton Hospital NHS, Dovehouse Street, London SW3 6LY, UK.
In the late 1980s, sublingual allergen immunotherapy (SLIT) was
proposed as an ‘alternative’ to subcutaneous allergen immunotherapy
(SCIT). 1,2 The main aim was to reduce systemic reactions and the risk of
anaphylaxis, which were frequently associated with SCIT and also to
increase the number of patients receiving allergen immunotherapy by
facilitating its regular use at home.
Over the years, through well-designed, well-powered studies, the
scientific community has increased the levels of evidence of SLIT
regarding its efficacy and safety. Nowadays, the use of SLIT has been
included in international guidelines for the treatment of allergic rhinitis
with or without conjunctivitis. 3
SLIT can be administered as drops or tablets for respiratory allergies due
to grass, tree and ragweed pollens, and house dust mites (HDM). Some
SLIT products are commercialised and routinely used in some European
countries. More recently, the US Food and Drug Administration (FDA) gave
the approval for three SLIT products (two for grasses; one for ragweed).
The clinical efficacy of SLIT is well documented in different double blind,
placebo-controlled, randomised clinical trials (DB PC RCTs) and meta-
analyses. 4 SLIT significantly reduces nasal and ocular symptoms scores,
reduces the use of relief medication and improves quality of life in both
adults and children with pollen respiratory allergy.
Large and complex clinical development programmes on SLIT have
been conducted in Europe and the US. Well-powered, well-designed
multinational DB PC RCTs using almost comparable clinical outcomes
and well-standardised sublingual products have demonstrated
sustained clinical efficacy of the SLIT tablets compared with placebo for
pollen respiratory allergy. These studies have also indicated a disease
modification 2 years after completion of 3 years of treatment with SLIT-
tablets for grass allergy. 5,6
Tou ch MEd ica l MEdia
More recently, the significant clinical effect of SLIT tablets for HDM
respiratory allergy have been demonstrated in adults with perennial
HDM rhinitis and asthma due to HDM. Nasal and ocular symptoms and
the risk of asthma exacerbations have been reduced after treatment
with SLIT-tablets for HDM.
SLIT’s safety profile is extremely good. 7 Symptoms are mainly localised
to the oral mucosa, such as itching/tingling of the lips or mouth, mild
local swelling of lips, sublingual area or tongue. These symptoms are
mild in severity and are self-limiting. 5–7 To re-assure the patient of the
safety profile and to inform about the expected local symptoms of
SLIT, it is always recommended that the first dose should be taken at
the doctors’ office. SLIT is prescribed to be self-administrated by the
patients in their homes.
Systemic reactions due to SLIT are rare. Very few ‘so-called’ anaphylactic
cases have been reported globally. There have been no fatalities related
Good adherence to SLIT is critical for its success, at least three to four
visits per year should be scheduled to evaluate SLIT’s adherence and
SLIT drops or tablets should be placed under the tongue, allowing
the allergen to be in contact for at least 2 minutes with the oral
mucosa. The proposed mechanism is that the allergens are captured by
tolerogenic dendritic cells and processed as small peptides. SLIT takes
advantage of this tolerogenic environment of the oral mucosa to promote
tolerance to the allergen. 8 Following the uptake of allergen during SLIT,
there is differentiation of T helper cell type 1 (Th1) and the induction
of interleukin (IL)-10-producing regulatory T cells. Following SLIT, allergic
disease-promoting Th2 responses shift to a Th1 inflammatory response,
and IL-10 and transforming growth factor (TGF)-β production by