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. Author manuscript; available in PMC: 2020 Jun 10.
Published in final edited form as: Int Forum Allergy Rhinol. 2018 Feb;8(2):108–352. doi: 10.1002/alr.22073

TABLE IX.D.4-1.

Evidence for the use of SLIT in the treatment of allergic rhinitis—systematic reviews and meta-analyses from the last decade

Study Year LOE Study design Study groups Clinical endpoint Conclusiona
Di Bona et al.815 2015 1a Meta-analysis of RCTs SLIT grass pollen tablets vs placebo for SAR Symptom and medication score Small improvement in symptom and medication scores vs placebo: (SMD −0.28; 95% CI, −0.37 to −0.19; p < 0.001) and (SMD −0.24; 95% CI, −0.31 to −0.17; p < 0.001).
Adverse events: 7/2259 SLIT patients were given epinephrine.
Leatherman et al.1692 2015 1a Systematic review of RCTs for SLIT doses SLIT for AR vs placebo Doses of the effective vs doses of non-effective SLIT Wide dose ranges between studies. For certain antigens, effective and non-effective dose ranges often overlap. For other allergens: insufficient data.
Devillier et al.1332 2014 1a Meta-analysis of RCTs Pollen SLIT vs pharmacotherapy vs placebo for SAR Relative clinical impactb Clinical impact: 5-grass pollen tablet > INCS > Timothy grass pollen tablet > montelukast > antihistamines
Makatsori et al.1693 2014 1a Systematic review of RCTs SLIT vs placebo Drop-out rates in SLIT and placebo groups No tendency for a skewed dropout ratio between SLIT and placebo groups. Confirms trial results are unbiased and SLIT appears to be safe.
Lin et al.1694 2013 1a Systematic review of RCTs Aqueous SLIT vs placebo for SAR (and asthma) Symptom and medication scores Moderate evidence aqueous SLIT reduces symptoms and medication use in AR/ARC.
Meadows et al.1617 2013 1a Meta-analysis of RDBPCTs, cost analysis SCIT and SLIT vs placebo for SAR Several efficacy variables, costs Symptom reduction with SCIT and SLIT is greater than placebo.
Di Bona et al.1696 2011 1a Meta-analysis of RDBPCTs Grass pollen SLIT vs placebo for SAR (and asthma) Symptom and medication scores SLIT vs placebo: Reduction in symptoms (SMD −0.32) and medication use (SMD −0.33). No epinephrine use.
Radulovic et al.1695 2011 1a Meta-analysis of RDBPCTs SLIT vs placebo for AR Symptom and medication scores SLIT vs placebo: Reduction in symptoms (SMD −0.49) and medication use (SMD −0.32). No epinephrine use.
Durham et al.1673 2016 1b Pooled analysis from RCTs SAR: grass or ragweed SLIT tablet vs pharmacotherapy.
PAR: HDM SLIT tablet vs pharmacotherapy.
Total Nasal Symptom Score SAR: SLIT numerically greater than montelukast and antihistamine; almost equal to mometasone furoate INCS.
PAR: SLIT effect numerically greater than all pharmacotherapy.
Maloney et al.1675 2015 1b Pooled analysis from RCTs Grass SLIT tablet vs placebo. Grass SLIT in AR patients with (24%) and without (76%) mild asthma. Treatment related AE frequency Severe asthma-related adverse events due to treatment in 6/120 SLIT and 2/60 placebo. No difference between the 2 groups. Both adults and children were included.
Creticos et al.1676 2016 2a Systematic review Patients treated with SLIT, started in-season, vs out-of-season vs placebo Serious treatment-related AE, systemic AE discontinuations 11 SLIT trials (n = 2668 subjects total). No epinephrine administration. 0% to 4% systemic AE with in-season vs 0% out-season initiation. 2 serious treatment-related AE with co-season SLIT initiation.
Oykhman et al.1677 2015 3a Systematic review of cohort studies Pregnant women with vs without SLIT or SCIT and their offspring. 422 pregnancies continuing AIT and 31 starting AIT. Pregnancy outcome, allergy in offspring No difference in prematurity, proteinuria, hypertension, congenital malformations, perinatal death. No fetal complications of 10/453 systemic reactions to SCIT. No altered risk of developing atopic disease in offspring.
SLIT or SCIT: children only
Larenas-Linnemann et al.1671 2013 2a Systematic review of RCTs Children with AR and/or asthma treated with SLIT vs placebo/open controls Symptom and medication scores Strong evidence that grass pollen SLIT in children reduces symptoms of AR. Moderate-low evidence for HDM SLIT.
Roder et al.1670 2008 2a Systematic review of RCTs Children 0–18 years with AR: any form of AIT vs placebo Symptom and medication scores Insufficient evidence that AIT in any form has a positive effect on AR in children.
SLIT vs SCIT
Chelladurai et al.1697 2013 1a Systematic review of RCT SCIT vs SLIT (and vs placebo) in AR Symptom and medication scores Low grade evidence favors SCIT over SLIT for AR symptom and medication reduction. Moderate evidence for nasal and eye symptom reduction.
Di Bona et al.1698 2012 1a Meta-analysis based comparison Grass pollen SCIT; placebo vs grass pollen SLIT; placebo in SAR SMD of symptom and medication scores SCIT more effective than SLIT (drops) and SLIT (tablet) for symptom and medication score reduction.
Nelson et al.1699 2015 1b Network meta-analysis of RCTs Grass pollen SLIT tablets vs placebo. Grass pollen SLIT drops vs placebo. Grass pollen SCIT vs placebo. Symptom and medication scores Symptom and medication scores with SCIT, SLIT tablets and drops all reduced vs. placebo, except for symptom score with SLIT drops.
Aasbjerg et al.1700 2015 2a Systematic review of RCTs, product information, registry AR patients receiving Phleum pratense SCIT, SLIT drops, or SLIT tablets vs placebo. (including 314 children.) Safety data Many products without structured collection of safety data. General safety assessment: SLIT safer than SCIT.
Dranitsaris and Ellis1701 2014 2a Systematic review of RCTs and indirect comparison Timothy grass tablet, 5-grass tablet, grass pollen SCIT vs placebo in SAR Efficacy, safety, cost for Canadian setting Symptoms: all IT treatments better than placebo. Costs for 5-grass tablet greater than costs for Timothy grass tablet and SCIT.
Calderon et al.1702 2013 2a Systematic review of RCTs Patients allergic to HDM, with AR and asthma, treated with HDM SCIT vs SLIT vs placebo Symptom score, IT schedule, dosing Improved symptom score vs placebo was observed more frequently for SCIT. Data is weak as the basic treatment parameters vary widely.
Dretzke et al.1703 2013 2a Systematic review of RCT and indirect comparison SCIT and aqueous SLIT vs placebo, SCIT vs SLIT in AR Symptom and medication scores Trend favoring SCIT over SLIT for AR symptom and medication score reduction. No conclusive results.
SLIT vs SCIT: children only
Kim et al.1672 2013 2a Systematic review of RCTs and indirect comparison Children with SAR (asthma): Aqueous SLIT vs SCIT vs placebo for SAR (and asthma) Symptom and medication scores In children, moderate evidence that SLIT improves AR symptoms and medication use, low evidence that SCIT is superior to SLIT for both outcomes.
Hoeks et al.1704 2008 2a Systematic review of RCTs SLIT vs placebo in children with asthma/ARC Symptom and medication scores Not enough evidence because of poor quality of the studies.
a

Only outcomes with statistically significance are mentioned here.

b

Clinical impact score = season-long nasal or total symptom scores: 100 × (scorePlacebo – scoreActive)/scorePlacebo.

AE = adverse event; AIT = allergen immunotherapy; AR = allergic rhinitis; ARC = allergic rhinoconjunctivitis; CI = confidence interval; HDM = house dust mite; INCS = intranasal corticosteroid; LOE = level of evidence; PAR = perennial allergic rhinitis; RCT = randomized controlled trial; RDBPCT = randomized double-blind placebo-controlled trial; SAR = seasonal allergic rhinitis; SCIT = subcutaneous immunotherapy; SLIT = sublingual immunotherapy; SMD = standardized mean difference.

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