Table 2 Characteristics of included studies

Valovirta et al. [27]

Results from the 5-year SQ grass sublingual immunotherapy tablet asthma prevention (GAP) trial in children with grass pollen allergy

812 (5–12 years)

SLIT with Phleum pretense grass vs. placebo

5 years (3 years treatment and 2 years follow-up)

Treatment with the SQ grass sublingual immunotherapy tablet significantly reduced the risk of experiencing asthma symptoms or using asthma medication (odds ratio = .66, P < .036) and the use of allergic rhinoconjunctivitis pharmacotherapy (27% less, P < .001)

Durham et al. [29]

Sublingual immunotherapy with once-daily grass allergen tablets: A randomized controlled trial in seasonal allergic rhinoconjunctivitis

855 (18–65 years)

SLIT with Phleum pretense grass vs. placebo

18 weeks

Moderate reductions of rhinoconjunctivitis symptoms (16%) and medications use (28%). Significantly better rhinoconjunctivitis quality of life scores (P = .006) and an increased number of well days (P = .041)

Ibañez et al. [30]

Safety of specific sublingual immunotherapy with SQ standardized grass allergen tablets in children

60 (5–12 years)

SLIT with Phleum pretense grass vs. placebo

1 February 2006 to 3 May 2006

Local reactions were reported at intervention group. The majority of these were local reactions in the mouth or throat and were mostly mild (71%) to moderate (27%) in severity and resolved within days. Two actively treated subjects withdrew from the study: one subject due to four adverse events (moderate eye pruritus, moderate pharyngolaryngeal pain, moderate non-cardiac chest pain and moderate dysphagia) and one subject due to a serious adverse event (asthmatic attack). The subjects recovered completely from the events. SLIT was in general tolerated

Didier et al. [32]

Optimal dose, efficacy, and safety of once-daily sublingual immunotherapy with a 5-grass pollen tablet for seasonal allergic rhinitis

628 (18–45 years)

Standardized 5-grass pollen extract (SLIT) vs. placebo

16 December 2004 to 5 September 2005)

Significantly reduction of rhinoconjunctivitis total score (3.58 ± 3.0, P = .0001; and 3.74 ± 3.1, P = .0006) Compared with placebo (4.93 ± 3.2). The efficacy and safety of sublingual immunotherapy with grass tablets was confirmed

Didier et al. [33]

Sustained 3-year efficacy of pre- and coseasonal 5-grass-pollen sublingual immunotherapy tablets in patients with grass pollen- induced rhinoconjunctivitis

633 (18–50 years)

5-grass pollen tablet (Oralair) vs. placebo

5 years (3-season treatment and 2-year follow-up phases)

The mean symptom score was reduced by 36% and 34.5% at season 3 in the 2 and 4-months pre and coseasonal active treatment groups compared with placebo group (P < .0001 for both). Reductions were observed in total symptom scores and the medication score, with a marked improvement in quality of life for active groups compared with placebo

Lozano et al. [34]

Assessing the Efficacy of Immunotherapy with a Glutaraldehyde-Modified House Dust Mite Extract in Children by Monitoring Changes in Clinical Parameters and Inflammatory Markers in Exhaled Breath

43 (6–14 years)

SIT group (8 μg/ml of Der p1 and 30 μg/ml of Der p2) and treatment group (control group)

Between 2009 and 2011

The SIT group presented with an improvement in asthma classification, a reduction in maintenance drug therapy and improved scores on the quality of-life questionnaire

Ferrés et al. [35]

Efficacy of high-dose sublingual immunotherapy in children allergic to house dust mites in real-life clinical practice

78 (6–18 years)

Retrospective, observational, monocentre study. Medical records of patients who received a standardized Dermatophagoides pteronyssinus + Dermatophagoides farinae extract

(300 IR/ml) were reviewed

Between 2001 and 2008

Patient evaluation of allergy severity revealed a highly significantly improvement between baseline and 6 months (P < .001). This improvement was maintained throughout the 4-year follow-up period. The use of medications was significantly reduced in the first 6 months (4.6 ± 2.5 points at baseline vs. .8 ± 1.6 points at 6 months visit, P < .001) and remained very low until the end of follow-up

Mosbech et al. [40]

Standardized quality (SQ) house dust mite sublingual immunotherapy tablet (ALK) reduces inhaled corticosteroid use while maintaining asthma control: A randomized, double-blind, placebo-controlled trial

604 (14 years or older)

SIT with standardized extracts of Dermatophagoides pteronyssinus and Dermatophagoides farinae vs. placebo

12 months

Mean difference between 6 SQ-HDM and placebo in the reduction in daily ICS (P = .004). The most common adverse events were local reactions in the mouth

Nolte et al. [41]

Efficacy of house dust mite sublingual immunotherapy tablet in North American adolescents and adults in a randomized placebo-controlled trial

1482 (12 years or older)

SLIT group (tablets with 12 SQ HDM dose) and placebo group

January 2013 to April 2015

Improvement In the total combined rhinitis score by 17% in the SIT group vs. placebo (P = .001). It was well tolerated and improved HDM-induced rhinitis symptoms