Table 8 Clinical efficacy of SLIT in children: update 2009 to September 2012

Randomized, double-blind, placebo-controlled

Wahn 2012 [11]

4–12

158/49

26/2

6-grass drops

8 mo

40 mcg group 5 daily

NS

RC(A)

All Pharm

SLIT vs placebo: Change in pre-post treatment higher for symptom-medication, symptom, & medication scores in SLIT group. Higher rate of positive response with SLIT (≥40% decrease of the AUC of the symptom-medication score).

SLIT vs placebo: Mean number of well days

Stelmach, 2012 [17]

6–18

Cont 20

1

Grass, drops

2 y

10 mcg group 5 daily Cont: for 2 y

NS

RCA

Stal

Both active groups vs placebo: Significant improvement, med+symp score, symptom score, FeNO.

Medication score in continuous group.

Pre-co 20

3

Plac 20

2

Pulmonary function tests, Metacholine challenge

Pre-co: 2 × 6 mo

Pre-coseasonal group vs placebo: significant reduction of med score

De Bot, 2012 [12]

6–18

126/125

15/17

Mite, drops

2 y

2.03 mcg Der p 1 twice per week. Total cumulative dose (2 y): 435 mcg

NS

RC

ART

No positive results

Total nasal symptom score, QoL, med score, well days

Yukselen 2012 [19]

Mean 10 (± 3)

SLIT 11

1

Mite, drops

1 y (+1 y obser-vation)

Dpt+Df: SLIT: 1000 TU/mL: 28 drops 3×/week.

4.2

R&A

AllerPhar

SCIT vs SLIT: SCIT reduced asthma symptoms significantly more than SLIT.

SLIT vs placebo: NS for all clinical parameters. NS for rhinitis and asthma VAS.

SCIT 10

0

Plac 11

1

SCIT vs placebo: Rhinitis symptoms, asthma symptoms, total symptoms, rhinitis meds, and asthma meds improved. VAS score was significantly reduced for both rhinitis and asthma.

SLIT and SCIT vs. baseline year: both improved almost all clinical parameters

SCIT: 3368 TU/4 wk

SCIT vs SCIT: NS for rhinitis symptoms and meds and asthma meds.

Blaiss 2011 [10]

5–17

175/169

33/29

Grass, tablets

6 mo

15 mcg Phl p5 daily

NS

RC(A)

ALK

SLIT: Improvements in daily symptoms (25%), daily meds (81%), total score (26%), and QoL (18%) (all P ≤ 0.04 vs. placebo).

Asthma symptoms

Kim 2011 [20]

1–11

11/7

0/0

Peanut, drops

12 m

2000 mcg daily (8 pumps)

No data on SCIT dosing

Peanut allergy

Greer

Food challenge: Significantly greater safe ingestion of peanut than placebo group; improvements in skin prick test and basophil responsiveness.

No statistically significant changes were found in IL-13 levels, the percentage of regulatory T cells, or IL-10 and IFN-gamma production.

Yonekura, 2010 [26]

7–15

20/11

1/2

Mite, drops

1 y

0.5 mcg Der f 1 once a week

20

RC

TOR

Active-placebo: week 30: reduced symptom score.

Active-placebo: combined sympt-med score

Change from initial (wks 0-3) to end (wks 37-40) in the active group: Decrease in symptoms and symptom-med score.

Mösges, 2010 [27]

6–14

27/27

0/0

Tree pollen drops

Updosing

30-90-150-300 IR each 30 min

NS

Asthma

Stal

Not an efficacy trial

No difference in PFR change between the active and placebo groups during updosing and no serious AEs.

Halken 2010 [7] (additional data to Wahn 2009 [3])

5–17

TOTAL 278 : 131/135

Grass tablet

6 mo

25 mcg Phl p 5 daily (300IR)

RC

Stal

Active-placebo: Total symptom score reduced over whole season and at peak pollen season. Nasal and ocular symptoms reduced. Rescue medication used less during whole and peak pollen season.

None

Nieminen 2010 [8] (subgroup of study Valovirta 2006 [6])

5–15

10 low

10 high

10 Plac

Birch-alder-hazel mix, drops

2 y

24,000 SQ-U/wk (3.6 mcg group 1), 200,000 SQ-U/wk (30 mcg grp 1)

0.5 and 4.5

RC(A)

ALK

Mechanistic study: Patients with elevated symptom and medication score: increase in allergen-induced PBMC mRNA IL-17 expression;

a positive and dose-dependent correlation SMS and IL-17 production. High-dose group vs placebo at 2 y: increase in FOXP3 mRNA expression. FOXP3 mRNA changes correlate with IL-10 and TGF-beta mRNA.

Stelmach 2009 [15]

6–17

20/15

5/10

Grass, drops

pre-co for 2 y

10 mcg group 5 grass drops daily

NS

A

Stal

SLIT vs Plac: asthma symptoms, nasal symptoms, nasal+asthma symptoms, medication score, nasal+asthma+med score.

SLIT vs Plac: ocular symptoms, total Asthma+nose+eye symptoms

Randomized controlled

Keet 2012 [21]

6–17

SLIT 10

0

Milk protein drops

14 mo

SLIT 7 mg, OIT-A 2000 mg, OIT-B 1000 mg milk protein daily

NS

CM

Food challenge passed by more OIT pts vs SLIT alone (SLIT 1, SLIT/OITB 6, SLIT/OITA 8)

3 of 6 desensitized OITB pts, 3 of 8 OITA pts regained hyperreactivity after 6 wk milk avoidance

SLIT start then:

OIT-A 10 OIT-B

10

0

0

Pajno 2011 [23]

8–16

Cont/coseasonal: 40/40

3/5

Grass drops

Cont: 3 y

8 mcg group 5, 5 times/week

NS

RA

Stal

Continuous vs coseasonal: 1^st year: symptoms+med, symptoms, chest symptoms, and med scores improved more with continuous SLIT.

3^rd year: no difference in clinical outcomes between continuous vs coseasonal SLIT

Coseasonal: 3 × 4 mo

Keles 2011 [24]

5–12

SCIT 15

4

HDM

18 mo

SCIT: 13 mcg Der p+f 1/mo

0.75

A (and R)

ALK

Active vs pharmacotherapy: SCIT→SLIT: all clinical parameters improved at 12 mo, half at 4 mo. SCIT: all but rhinitis score improved at 12 mo. SLIT: only asthma med improved at 12 mo.

SLIT vs pharmacotherapy: only asthma med improved.

SCIT: alum adsorbed, SLIT drops

SLIT 15

2

SLIT: 0.75 mcg Der p+f 1 3 times/week

build-up SCIT

1

Pharmacotherapy: no clinical parameters improved

then SLIT 15

Pharmacotherapy

15

3

Within group: Asthma medication and asthma attacks reduced at 4, 12, 18 mo compared to baseline with SCIT and SCIT→SLIT, reduced at 12 mo with SLIT.

Marogna 2011 [121]

5–17

SLIT 34/ Cetirizine 34

3/4

HDM (not specified drop-tab)

36 mo

1000 AU 1/w

?

R2+A

Lofarma

SLIT non-smoking: clinical scores, nasal CS, B2 use, and pulmonary function tests all improved

Cetirizine + non-smoking: clinical and pulmonary function tests

50% of each group: passive cigarette smoke*

SLIT smoking: all showed a trend to improvement, but only MEF25 was statistically significant.

Cetirizine + Smoking: all parameters worsened

Pozzan 2010 [28], low quality, only once per year evaluation by patient

10–65

SLIT 34, Control 18

1/0

Alternaria drops

36 mo

1 dosis SLITone daily

?

R (A)

ALK

Active vs control: Symptom score reduced, med score reduced

Active vs control: No med score reduction

Active pre-post: med score reduced

Eifan 2010 [14]

5–10 y

SLIT16, SCIT16, Pharma 16

1/2

HDM SCIT: alum adsorbed, SLIT drops

12 mo

Dosing not clear (SLIT: 3.8 mcg Der p+f 1 3 times/wk

2.2?

A (R)

ALK

SLIT and SCIT vs pharmacotherapy: total rhinitis symptoms, asthma symptoms, medication, and VAS score.

SLIT vs SCIT: no difference in total rhinitis symptoms, asthma symptoms, medication, or VAS score.

SCIT: 22.2 mcg Der p+f 1/m)

Open controlled, no randomization

Aquistapace 2009 [29]

6–18

cases 90/control81

NA

Several, drops

2 y

varied

NS

RC(A)

ALK (SLITone)

SLIT vs controls: reduced symptoms, med score, new sensitizations.

SLIT vs control: asthma symptoms

Observational, prospective

Lee 2011 [13]

mean 14.7 (4–53)

Mono-sensitized 70 Multi 64

NS

HDM, drops

12 mo

5 drops 1000 STU/mL Dpt-Df 3/week

NS

R

ALK

none

Mono- and multisensitized symptom and medication scores: all improved. No difference between any variable.

Roger 2011 [22]

4–15 (total subjects 4–64)

122 (total n = 218)

none

HDM, drops

Updosing

Every 30 min: 30-60-120-240IR

30

R and/or A

Stal

8 systemic reactions (3 moderate), all continued SLIT. Higher frequency of AEs in asthmatic patients.

No difference in frequency or severity of AEs in patients under 15 y.

Observational, retrospective

Trebuchon, 2012 [18]

735 pts 5–18 (1289 pts total)

No active or control groups

No active or control groups

HDM, drops

2+ y

Variable, most 300IR daily

No comparison possible

Resp. allergy

Stal, some ALK

Descriptive study of how SLIT is given, dosing schedules, duration, etc. Treatment ‘(very) effective’, according to physician: 82%. Reduction in asthma medication: 26% stopped taking ICS.