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

From: Sublingual immunotherapy: World Allergy Organization position paper 2013 update

AUTHOR, year [reference] Age (y) A/P Drop-out (A/P) Allergen, drop or tablet Duration Dose (mcg/dose and dosing frequency) Versus SCIT Disease Manu-facturer Main positive results Negative results
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: 1st year: symptoms+med, symptoms, chest symptoms, and med scores improved more with continuous SLIT. 3rd 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.
  1. *parental smoking (at least 20 cigarettes per day).
  2. Abbreviations: AE, adverse event, A/P, active/placebo; NS, not signficant; HDM, house dust mite; Cont, continuous; plac, placebo; pre-co, pre-coseasonal; QoL, quality of life; TU, therapeutic units; AU, area under the curve; med(s), medication(s); OIT, oral immunotherapy; AE, adverse event; VAS, visual analog scale; pts, patients; PFR, peak flow rate; SAE, serious adverse event; RC, rhinoconjunctivitis; RCA, rhinoconjunctivitis and (mild) asthma; [I]CS, [inhaled] corticosteroid; STAL, Stallergenes; GRE, Greer; ALK, ALK-Abelló; TOR, Torii Pharmaceutical, Japan.