Table 1.

Randomized, double-blind, placebo-controlled trials of SLIT performed since 2009

Author, year [reference]	Ages (y)	A/P	Dropouts (A/P)	Allergen	Duration	Dose and administration	Disease	Manu-facturer	Main positive results	Negative results
Horak, 2009 [43]	18-50	45/44	3/4	Grass	4 mo	20 mcg	RC	STA	Significant reduction in RC score in Vienna challenge chamber at 4 mo in SLIT vs baseline and vs placebo (the reduction vs placebo was 29%)	Nasal airflow
						Phl p 5/day				Weight of secretions
						Tablets				Basophil activation
									Increased IgE and IgG4
Skoner, 2010 [46]	18-50	39 med	4	Ragweed	6 mo	4.8 or 48 mcg	RC	GRE	Combined symptoms+drugs and drug score versus placebo	Nasal challenge, IgE
		36 high	5			Amb a 1/day				Symptom score
		40 plac	3			Metered pump				during peak season
Cortellini, 2010 [42]	16-44	15/12	0/1	Alternaria	10 mo	60 mcg Alt a 1 cumul. 6 mcg/mo	RCA	ANA	Significant reduction in combined score (-38% versus placebo).	Specifcic IgE and IgG4
						Drops			Significant reduction in skin reactivity
Panizo, 2010 [45]	18-65	52/26	2/1	Grass	5 mo	25 mcg Phl p 5/day Tablets	RC	ALK	Increase in IgE, IgG4, and IgE blocking activity only in active
Yonekura, 2010 [48]	7-15	20/11	1/2	Mite	1 y	0.5 mcg Der f 1 once a week	RC	TOR	Significant decrease in symptoms and combined score in wk 0–3 and 37–40 only in SLIT	Medication score
Blaiss, 2011 [40]	5-17	349/358	33/30	Grass	6 mo	450 g Phl p 5/mo	RC	STA	Significant reduction in combined score (-26%) versus placebo. Quality of Life 38% improvement vs placebo	Asthma symptoms
Nelson, 2011 [44]	18-63	213/225	33/33	Grass	10 mo	450 mcg Phl p 5/mo Tablets	RCA	STA	Significant reduction in combined score (-20%and medication score (-20%) versus placebo	Daily medication score
Bush, 2011 [41]	18-50	High 10	2	Mite	18 mo	70 or 1 mcg	RA	GRE	Significant reduction in specific bronchial reactivity	Symptoms and medication scores
		Low 10	3	(Der f)		Der f 1 per dose.
		Pla 11	5			Drops
									Increase in IgG4
Stelmach, 2012 [47]	6-18	Cont 20	3	Grass	2 y	Cumulative 7.3 and 3.6 mcg Phl p 5. Drops	RCA	ALK	Significant improvement in drugs +symptoms with both continuous and precoseasonal regimen. Reduction in FeNO	Symptom score
		Prec 20	1							Medication score
		Pla 20	2							Pulmonary function
de Bot, 2012 [53]	6-18	126/125	15/17	Mite	2 y	4.06 mcg	RC	ART		Symptom score
						Der p 1/week				QoL
						Drops				Medication score
										Well days
Ahmadiasfshar 2012 [49]	5-18	12/12	2/2	Grass	6 mo	Cumulative: about 6,000 IR Spray	RC	STA	Significant improvement in symptom and medication scores
									Reduction of skin wheal diameter
Wahn, 2012 [54]	4-12	158/49	26/2	Grass	8 mo	Cumulative: 7.2–8.4 mg group 5	RC	ALL	Significant reduction versus placebo in combined symptom/medication and individual scores
						Drops
Cox, 2012 [51]	18-65	233/240	26/17	Grass	6 mo	Cumulative: approx 3.6 mg group 5 allergen.	RC	STA	Significant reduction of combined symptom + medication score (-28% versus placebo) and overall quality of life	Itchy nose symptom score versus placebo
						Tablets
Bozek, 2013 [50]	60-75	51/57	7/9	Mite	3 y	NS	RC	STA	Total nasal scores decreased by 44% from baseline in SLIT and by 6% in placebo.	Symptoms after specific nasal provocation versus placebo
									Medication score decreased 35% from baseline in SLIT group.
Wang, 2013 [55]	4-65	60/60	12/23	Mite	6 mo	NS	RC	ZHE	Significant decrease in each individual rhinitis symptom versus placebo starting from week 14.	No change versus placebo in medication intake
Nolte, 2013 [18]	18-50	High 187	142	Ragweed	1 y	6 or 12 mcg	RCA	MSD	Significant decrease in combined symptom + medication score for both active groups VS placebo (21% and 27%)
		Low 190	overall			Amb a 1 daily
		Pla 188				Tablets
Creticos, 2013 [52]	18-50	Low 197	40	Ragweed	1 y	Cumulative dose	RCA	MSD	Only the high dose decreased daily symptom, medication, and combined scores during peak pollen season and whole season versus placebo.	Low dose overall less effective than the 2 other doses on symptoms/medications in peak pollen and whole season
		Med 195	43			4.38 mg Amb a 1
		High 194	57			Tablets
		Pla 198	38

Abbreviations: A/P active/placebo, NS not stated, RC rhinoconjunctivitis, RCA rhinoconjuntivitis/asthma, STA Stallergenes, GRE Greer, ANA Anallergo, ALL Allergopharma, ALK ALK-Abellò, MSD Merck Sharp and Dome, TOR Torii Pharmaceuticals, ZHE Zheng Wolwo Bio Pharma.