Sublingual Immunotherapy in Children: Recent Experiences

Abstract and Introduction

Abstract

Purpose of review Sublingual immunotherapy (SLIT) is indicated for the use in pediatric patients suffering from allergic rhinitis or allergic rhinoconjunctivitis caused by environmental allergens, such as ragweed pollen, grass pollen, and dust mite. This review focuses on recent and relevant studies associated with the use of SLIT for these allergens in children by examining efficacy, safety, and immunological data in comparison to subcutaneous immunotherapy, therapeutic treatments, and placebo.

Recent findings In several of the case studies examined in this article, involving mainly grass and dust mite allergic patients, SLIT has been shown to have similar efficacy to subcutaneous immunotherapy. SLIT has been proven as a safer therapy. In comparing the adverse events related to both therapies, SLIT has fewer cases of anaphylaxis and fewer incidents of local reactions of mild-to-moderate severity. In comparison to therapeutic treatments and placebo, SLIT significantly improved symptom and medication scores. In addition to allergic rhinitis and allergic rhinoconjunctivitis, additional uses for SLIT in pediatric patients, such as asthma, atopic dermatitis, and food allergies, are under development.

Summary SLIT treatment is a well tolerated and effective approach to treat allergic rhinitis and allergic rhinoconjunctivitis in pediatric patients. Three SLIT tablets are currently approved by the US Food and Drug Administration to treat grass and ragweed allergies. The research discussed in this review will further the knowledge of physicians searching for an alternative treatment for their pediatric patients.

Introduction

Sublingual immunotherapy (SLIT) is a type of specific immunotherapy utilized to treat allergic rhinitis or allergic rhinoconjunctivitis (ARC).^[1] SLIT is ideally suited for use in children because it is needleless and convenient (given at home). Over 75 clinical research studies have been performed to prove the clinical efficacy of SLIT with at least 20 of those trials including only children.^[1,2] SLIT has become recognized as a low-risk, high-benefit option for adults and children suffering from allergic rhinitis or ARC, and more recently, clinical trials have begun to demonstrate efficacy in diseases such as asthma, atopic dermatitis, and food allergies.^[3] The most-studied SLIT allergens for pediatrics are dust mite and grass. Currently, three nature-based tablets have gained approval by the US Food and Drug Administration (FDA), two grass (Oralair and Grastek) and one ragweed (Ragwitek).^[4] No SLIT dust mite tablets have been approved in the US, Grastek (Merck Sharp & Dohme Corp. Whitehouse Station, New Jersey, USA) is approved by FDA for individuals 5–65 years old, Oralair (Stallergenes S.A., Antony, France) is approved for individuals 10–65 years old, and Ragwitek (Merck Sharp & Dohme Corp. Whitehouse Station, New Jersey, USA) is approved for individuals 18–65 years old. Twenty-eight research trials conducted from 2009 to 2012 included children.^[4] SLIT has been proven as a well tolerated therapy for not only adults but also children.^[5] Specifically, children did not have any more adverse events than adults in any SLIT studies.^[3] The use, benefit, and safety of SLIT in children and recent, relevant clinical trials, which are presented in Table 1,^[6,7–20] will be discussed.

Table 1. Sublingual immunotherapy in pediatric patients
Study (year)	Sample size[ age (years)]	Diagnosis	Allergen (s)	Study treatment arms	Double-blind	Study duration	Results
De Castro et al. (2013) [6]	140 (6–14)	Allergic rhinitis Allergic asthma	Grass pollen or house dust mite	SLIT vs. symptomatic therapy	No	36 months	SLIT significantly decreased asthma and allergic rhinitis symptom scores
Nolte et al. (2013) [7]	565 (18–50)	Allergic rhinitis/rhinoconjunctivitis	Ragweed pollen	SLIT vs. placebo	Yes	12 months	Daily medication and daily allergic rhinitis symptom scores significantly decreased compared with placebo
Pastorello et al. (2013) [8]	47 (12–45)	Allergic rhinitis	Grass pollen	SLIT	Yes	24 months	SLIT caused a significant decrease in use of oral antihistamines and nasal decongestants in patients who were unresponsive to drugs
Wahn et al. (2008) [9]	278 (5–17)	Allergic rhinoconjunctivitis	Grass pollen	SLIT vs. placebo	Yes	7 to 8 months	The SLIT treatment reduced symptom and medication scores in both children and adolescents
Blaiss et al. (2011) [10]	345 (5–17)	Allergic rhinoconjunctivitis with or without asthma	Grass pollen	SLIT vs. placebo	Yes	23 weeks	SLIT was found effective in both children and adolescents through reducing the total medication and symptom scores in comparison to the placebo group. The quality of life also improved for these patients by 18% in comparison to placebo
Maloney et al. (2014) [11 ]	1501 (5–65)	Allergic rhinitis/rhinoconjunctivitis with/without asthma	Grass pollen	SLIT vs. placebo	Yes	26 months	SLIT was effective in treating allergic rhinitis in North American adults and children
Marcucci et al. (2012) [12]	30 (mean age 11.3)	Allergic rhinitis	Grass pollen	SLIT vs. no treatment	UNK	5 months	SLIT treatment of grass pollen enhances specific immunoglobulin E synthesis, which is involved in the same allergen components that occur during natural exposure
Aydogan et al. (2013) [13]	22 (5–10)	Allergic rhinitis	Dermatophagoides pteronyssinus or D. farinae	SLIT vs. placebo	Yes	12 months	SLIT significantly improved skin, nasal, and bronchial reactivity
Bergmann et al. (2013) [14]	595 (18–50	Allergic rhinitis	D. pteronyssinus or D. farinae	SLIT vs. placebo	Yes	12 months	SLIT therapy at 300 IR and 500 IR was well tolerated and significantly decreased symptom scores as compared with placebo
Yukselen et al. (2013) [15 ]	32 (mean average 11.5	Allergic rhinitis Asthma	D. pteronyssinus or D. farinae	SLIT vs. SCIT	Yes	24 months	No significant difference found between SCIT and SLIT symptom scores
Trebuchon et al. (2014) [16 ]	736 (5–17)	Allergic rhinitis with or without asthma	D. pteronyssinus or D. farinae	SLIT	No	24 months	SLIT was found to be effective and satisfactory by the patients in this 'real-life' setting retroactive study
Shao et al. (2014) [17 ]	264 (3–13)	Allergic rhinitis with or without asthma	D. farinae	SLIT vs. no treatment	No	12 months	SLIT significantly decreased symptom and VAS scores from baseline and significantly reduced rhinitis medication scores over the control group
Chen et al. (2013) [18]	122 (3–14)	Allergic rhinitis Allergic asthma	D. farinae	SLIT at ages 3–6 vs. SLIT at ages 7–14	No	36 months	No significant difference between the two groups of children
Kim et al. (2011) [19]	18 (1–11)	Food allergy	Peanut	SLIT vs. placebo	Yes	12 months	After 6 months of treatment, SLIT patients were able to ingest significantly more peanuts than the placebo group
Fleischer et al. (2013) [20]	40 (12–37)	Food allergy	Peanut	SLIT vs. placebo	Yes	44 weeks	After 44 weeks of SLIT, patients were able to ingest 10 times as much peanut as they could at baseline

Table 1. Sublingual immunotherapy in pediatric patients

Study (year)

Sample size[ age (years)]

Diagnosis

Allergen (s)

Study treatment arms

Double-blind

Study duration

Results

De Castro et al. (2013) [6]

140 (6–14)

Allergic rhinitis Allergic asthma

Grass pollen or house dust mite

SLIT vs. symptomatic therapy

36 months

SLIT significantly decreased asthma and allergic rhinitis symptom scores

Nolte et al. (2013) [7]

565 (18–50)

Allergic rhinitis/rhinoconjunctivitis

Ragweed pollen

SLIT vs. placebo

Yes

12 months

Daily medication and daily allergic rhinitis symptom scores significantly decreased compared with placebo

Pastorello et al. (2013) [8]

47 (12–45)

Allergic rhinitis

Grass pollen

SLIT

Yes

24 months

SLIT caused a significant decrease in use of oral antihistamines and nasal decongestants in patients who were unresponsive to drugs

Wahn et al. (2008) [9]

278 (5–17)

Allergic rhinoconjunctivitis

Grass pollen

SLIT vs. placebo

Yes

7 to 8 months

The SLIT treatment reduced symptom and medication scores in both children and adolescents

Blaiss et al. (2011) [10]

345 (5–17)

Allergic rhinoconjunctivitis with or without asthma

Grass pollen

SLIT vs. placebo

Yes

23 weeks

SLIT was found effective in both children and adolescents through reducing the total medication and symptom scores in comparison to the placebo group. The quality of life also improved for these patients by 18% in comparison to placebo

Maloney et al. (2014) [11 ]

1501 (5–65)

Allergic rhinitis/rhinoconjunctivitis with/without asthma

Grass pollen

SLIT vs. placebo

Yes

26 months

SLIT was effective in treating allergic rhinitis in North American adults and children

Marcucci et al. (2012) [12]

30 (mean age 11.3)

Allergic rhinitis

Grass pollen

SLIT vs. no treatment

UNK

5 months

SLIT treatment of grass pollen enhances specific immunoglobulin E synthesis, which is involved in the same allergen components that occur during natural exposure

Aydogan et al. (2013) [13]

22 (5–10)

Allergic rhinitis

Dermatophagoides pteronyssinus or D. farinae

SLIT vs. placebo

Yes

12 months

SLIT significantly improved skin, nasal, and bronchial reactivity

Bergmann et al. (2013) [14]

595 (18–50

Allergic rhinitis

D. pteronyssinus or D. farinae

SLIT vs. placebo

Yes

12 months

SLIT therapy at 300 IR and 500 IR was well tolerated and significantly decreased symptom scores as compared with placebo

Yukselen et al. (2013) [15 ]

32 (mean average 11.5

Allergic rhinitis Asthma

D. pteronyssinus or D. farinae

SLIT vs. SCIT

Yes

24 months

No significant difference found between SCIT and SLIT symptom scores

Trebuchon et al. (2014) [16 ]

736 (5–17)

Allergic rhinitis with or without asthma

D. pteronyssinus or D. farinae

SLIT

24 months

SLIT was found to be effective and satisfactory by the patients in this 'real-life' setting retroactive study

Shao et al. (2014) [17 ]

264 (3–13)

Allergic rhinitis with or without asthma

D. farinae

SLIT vs. no treatment

12 months

SLIT significantly decreased symptom and VAS scores from baseline and significantly reduced rhinitis medication scores over the control group

Chen et al. (2013) [18]

122 (3–14)

Allergic rhinitis Allergic asthma

D. farinae

SLIT at ages 3–6 vs. SLIT at ages 7–14

36 months

No significant difference between the two groups of children

Kim et al. (2011) [19]

18 (1–11)

Food allergy

Peanut

SLIT vs. placebo

Yes

12 months

After 6 months of treatment, SLIT patients were able to ingest significantly more peanuts than the placebo group

Fleischer et al. (2013) [20]

40 (12–37)

Food allergy

Peanut

SLIT vs. placebo

Yes

44 weeks

After 44 weeks of SLIT, patients were able to ingest 10 times as much peanut as they could at baseline

Sublingual Immunotherapy in Children: The Recent Experiences

Abstract and Introduction

Abstract

Introduction

Tables

References

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