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Table 1 Characteristics of included studies

From: Allergen immunotherapy for allergic rhinoconjunctivitis: a systematic overview of systematic reviews

References Title Countrys Number of studies included (number of participants) Type of immunotherapy (intervention vs. comparator) Type of allergen/AIT protocol Timeframe over which evaluation undertaken Authors’ results & conclusions Risk of bias
Calderon et al. [25] Allergen injection immunotherapy for seasonal allergic rhinitis UK 51 (2871: 1645 verum; 1226 placebo) SCIT versus placebo Pollen/continuous AIT Up to February 2006 SCIT is a safe and valid treatment option in pts (children and adults) with SAR. MAs showed an overall reduction in SS (SMD −0.73 (95% CI −0.97 to −0.50, P < 0.00001) and MS (SMD of −0.57 (95% CI −0.82 to −0.33, P < 0.00001) in the IT group. Clinical interpretation of the effect size is difficult. Adrenaline was given in 0.13% (19 of 14,085 injections) of those on IT and in 0.01% (1 of 8278 injections) of the placebo group for treatment of AEs. There were no fatalities Low
Di Bona et al. [27] Efficacy of grass pollen allergen sublingual immunotherapy tablets for seasonal allergic rhinoconjunctivitis: a systematic review and meta-analysis Italy 13 (4659) SLIT (only tablets) versus placebo Grass pollen/cluster AIT Up to April 2014 There is small benefit in active group in reducing the SS (SMD, −0.28; 95% CI, − 0.37 to −0.19; P < .001) and the MS (SMD, −0.24; 95% CI, −0.31 to −0.17; P < .001) in SAR pts. The magnitude of benefits is lower in children. Also, safety data are not encouraging (7 pts in the SLIT group reported severe treatment-related AEs requiring adrenaline) Moderate
Di Bona et al. [26] Efficacy of sublingual immunotherapy with grass allergens for seasonal allergic rhinitis: a systematic review and meta-analysis Italy 19 (2971) SLIT versus placebo Grass pollen/pre-coseasonal and continuous AIT Up to January 2010 SLIT with grass allergens is effective in significantly reducing both SS (SMD, –0.32; 95% CI, –0.44 to –0.21; P < .0001) and MS (SMD, –0.33; 95% CI, –0.50 to –0.16; P < .0001) compared to placebo. However, the magnitude of effectiveness is low. Sub-analyses show major magnitude of effectiveness in adult’s versus children. A course of treatment ≤12 wks with a monthly allergen dose of 450 mcg seems to be the best treatment option Moderate
Dranitsaris et al. [37] Sublingual or subcutaneous immunotherapy for seasonal allergic rhinitis: an indirect analysis of efficacy, safety and cost Canada 20 (6405) SLIT (tablets: Oralair/Grazax) versus placebo compared with SCIT versus placebo Grass/pre-coseasonal and continuous AIT Up to December 2012 The indirect analysis suggests improved efficacy in AR symptom control with Oralair™ (SMD, −0.21; P = 0.007) and Grazax™ (SMD, −0.18; P = 0.018) over SCIT and comparable safety. In Canada, Oralair™ is associated with cost savings against year-round SCIT ($2471), seasonal SCIT ($948) and Grazax™ ($1168) during the first year of therapy High
Dretzke et al. [36] Subcutaneous and sublingual immunotherapy for seasonal allergic rhinitis: a systematic review and indirect comparison UK SCIT versus placebo: 17 RCTs; SLIT versus placebo: 11 RCTs; SCIT versus SLIT: 1 RCT SCIT and SLIT versus placebo and SCIT versus SLIT Pollen, mold/heterogeneous protocols August 2009 to April 2011 SCIT and SLIT are effective versus placebo (strength of effectiveness higher in adults than in children) in improving SS [(SCIT: SMD, 20.65; 95% CI, 20.85 to 20.45; P < .00001); (SLIT: SMD, 20.33; 95% CI, 20.42 to 20.25; P < .00001)]; MS [(SCIT: SMD, 20.55; 95% CI, 20.75 to 20.34; P < .00001); (SLIT: SMD, 20.27; 95% CI, 20.37 to 20.17; P < .00001)]; HR-QoL. The superiority of effectiveness of one route of administration over the other cannot be consistently demonstrated Low
Erekosima et al. [22] Effectiveness of subcutaneous immunotherapy for allergic rhinoconjunctivitis and asthma: a systematic review USA 61 (3577): 12 AA, 23 AR, and 26 combined AA & AR RCTS SCIT versus placebo/SCIT versus pharmacotherapy/SCIT versus SCIT (different regimens) Pollen, HDM, mold, animal dander/heterogeneous protocols 1967 to May 2012 Moderate to strong evidence supports the effectiveness of SCIT for treatment of adult pts with AR and/or AA, particularly with single-allergen IT regimens. AEs to SCIT are common, but no deaths are reported in the included studies High
Feng et al. [23] Cluster subcutaneous allergen specific immunotherapy for the treatment of allergic rhinitis China 8 (567) Cluster SCIT versus placebo/cluster SCIT versus conventional SCIT Pollen, HDM, animal dander/heterogeneous protocols 1980 to May 2013 Though cluster SCIT is safe, because of limited evidence authors could not conclude affirmatively that cluster SCIT is an effective option (in terms of reduction of SS and MS) for the treatment of patients with ARs Moderate
Hoeks et al. [30] (Dutch study translation not possible) Sublingual immunotherapy in children with asthma or rhinoconjunctivitis: not enough evidence because of poor quality of the studies; a systematic review of literature        
Kim et al. [35] Allergen-specific immunotherapy for pediatric asthma and rhinoconjunctivitis: a systematic review USA SCIT versus placebo: 13 RCTs (920); SLIT versus placebo: 18 RCTs (1583); SCIT versus SLIT: 3 RCTs (135) SCIT versus placebo/SLIT (only aqueous formulation) versus placebo/SCIT versus SLIT (only aqueous formulation) Pollen, HDM, mold/heterogeneous protocols Up to May 2012 Both SCIT and SLIT are effective for the treatment of AA and AR in children. The strength of evidence is moderate that SCIT improves AA and AR SS and low that SCIT improves AA MS. Strength of evidence is high that SLIT improves AA SS and moderate that SLIT improves AR SS and AR MS. The evidence is low to support SCIT over SLIT for improving AA and AR SS or MS Moderate
Lin et al. [28] Sublingual immunotherapy for the treatment of allergic rhinoconjunctivitis and asthma: a systematic review USA 63 (5131): SLIT versus placebo 46 RCTs; SLIT versus another SLIT protocol without a placebo group 9 RCTs; SLIT versus ST without placebo 8 RCTs SLIT versus placebo/SLIT versus ST/SLIT versus SLIT (different regimens) Pollen, HDM, mold/heterogeneous protocols Up to December 2012 There is moderate grade level of evidence to support the effectiveness of SLIT for AR and AA in adults and children. No life-threatening AEs were noted in this review High
Meadows et al. [34] A systematic review and economic evaluation of subcutaneous and sublingual allergen immunotherapy in adults and children with seasonal allergic rhinitis UK SCIT versus placebo: 17 RCTs; SLIT versus placebo:11 RCTs; SCIT versus SLIT:16 RCTs SCIT versus placebo/SLIT versus placebo/SCIT versus SLIT Pollen/conventional protocol Up to April 2011 Effectiveness (SS, MS, HR-QoL) of both SCIT and SLIT versus placebo has been demonstrated in adults with SAR +/− seasonal AA. There is less evidence for children, but some results in favour of SLIT were statistically significant. However, overall the extent of this effectiveness in terms of clinical benefit is unclear. Both SCIT and SLIT may be cost-effective compared with pharmacotherapy from around 6 years (threshold of £20,000–30,000 per QALY) Low
Purkey et al. [24] Subcutaneous immunotherapy for allergic rhinitis: an evidence based review of the recent literature with recommendations USA 12 (1512) SCIT versus placebo/SCIT versus SLIT Pollen, HDM/heterogeneous protocols From 2006 to 2011 SCIT improves SS, MS, SMS and HR-QoL. Authors recommend SCIT for pts with seasonal or perennial AR not responsive to conservative medical therapy, and whose symptoms significantly affect HR-QoL High
Radulovic et al. [29] Systematic reviews of sublingual immunotherapy (SLIT) UK 60 RCTs in SR, 49 suitable for MA; Age: 34 RCTs in adults and 15 in children SLIT versus placebo Pollen, HDM, cat/heterogeneous protocols Up to August 2009 SLIT is safe and effective in reducing AR- SS (SMD, −0.49; 95% CI −0.64 to −0.34, P < 0.00001) and -MS (SMD −0.32; 95% CI −0.43 to −0.21, P < 0.00001) compared with placebo. The magnitude of benefit appears to be major for SLIT to HDM. No difference of efficacy were found between children and adults. There was too much heterogeneity to evaluate differences between different sublingual preparations (drops vs. tablets) and doses and about HR-QoL Low
Roder et al. [38] Immunotherapy in children and adolescents with allergic rhinoconjunctivitis: a systematic review The Netherlands 28 RCTs (1619): 6 SCIT, 4 LNIT, 7 OIT and 11 SLIT SCIT/SLIT/LNIT/OIT versus placebo/ST/different administration forms of IT Different pollen or HDM or mold/continuous or cluster protocol Up to June 2006 There is at present insufficient evidence that IT in any administration form has a positive effect on symptoms and/or medication use in children and adolescents with AR High
Sopo et al. [32] Sublingual immunotherapy in asthma and rhinoconjunctivitis; systematic review of paediatric literature Italy 8 RCTs SLIT versus placebo Pollen, HDM/conventional protocol Up to June 2003 SLIT can be currently considered to have low to moderate clinical efficacy in children ≥4 yrs of age, monosensitised to HDM, and suffering from mild to moderate persistent AR. No clinically relevant results are shown, independently from statistical significance, in the use of SLIT for AA and AR due to seasonal allergens and for AR to HDM in children High
Wilson et al. [31] Sublingual immunotherapy for allergic rhinitis: systematic review and meta-analysis UK 22 (979) SLIT versus placebo/SLIT versus SCIT Pollen, animal dander, HDM Up to September 2002 SLIT is effective and safe. Overall there was a significant reduction in both SS (SMD −0.42, 95% CI −0.69 to −0.15; P = 0.002) and MS (SMD −0.43 95% CI −0.63 to −0.23; P = 0.00003) following SLIT. However, no significant benefit was found in those studies involving only children, though they had a sample size too small to be conclusive. There were no significant differences in benefit according to the allergen administered. Increasing duration of treatment does not clearly increase efficacy. The total dose of allergen administered may be important but insufficient data was available to analyse this factor High
Zhang et al. [33] Efficacy and safety of dust mite sublingual immunotherapy for pediatric allergic rhinitis: A meta-analysis China 9 RCTs (663) SLIT versus placebo HDM Up to May 2014 SLIT is effective and safe. There was no significant difference in improvement in children with allergic rhinitis nasal symptom score aspect [SMD = 0.06, 95% CI (−0.13, 0.25), P = 0.55]. However, the medication use in intervention group significantly decreased compared with placebo [SMD = −0.61, 95% CI (−0.94 to −0.27), P = 0.0004] Moderate
  1. AA allergic asthma, AE adverse event, AR allergic rhinitis, HDM house dust mite, HR-QoL health related quality of life, IT immunotherapy, LNIT nasal immunotherapy, MA meta-analysis, MS medication scores, OIT oral immunotherapy, P P value, pt patient, QALY quality-adjusted life-year, RCT randomized controlled trial, SAR seasonal allergic rhinitis, SR systematic review, SCIT subcutaneous immunotherapy, SLIT sublingual immunotherapy, SS symptom scores, ST standard treatment (anti-H1, …)