Background
Methods
Search strategy
Inclusion criteria
Patient characteristics
Interventions of interest and comparator
Study designs
Study outcomes
Study selection
Quality assessment strategy
Data extraction, analysis and synthesis
Results
Characteristics of included 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 |
Quality assessment of systematic reviews
References | Focused question | Inclusion of appropriate studies | Inclusion of eligible studies | Quality assessment of studies | Appropriateness of synthesis | Overall results of review | Applicability to local populations | Considering all relevant outcomes | Benefits versus harms/costs | Overall quality assessment |
---|---|---|---|---|---|---|---|---|---|---|
Calderon et al. [25] | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | n/a | ✓ | ✓ | High |
Di Bona et al. [27] | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | n/a | ✓ | ✓ | High |
Di Bona et al. [26] | ✓ | ✓ | X | ✓ | ✓ | ✓ | n/a | ✓ | n/a | Moderate |
Dranitsaris et al. [37] | ✓ | ✓ | Unclear | Unclear | ✓ | ✓ | n/a | ✓ | ✓ | Low |
Dretzke et al. [36] | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | n/a | ✓ | ✓ | High |
Erekosima et al. [22] | ✓ | ✓ | ✗ | ✓ | n/a | ✓ | n/a | ✓ | ✓ | Moderate |
Feng et al. [23] | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | n/a | ✓ | ✓ | High |
Hoeks et al. [30] | ||||||||||
Kim et al. [35] | ✓ | ✓ | ✗ | ✓ | ✓ | ✓ | n/a | ✓ | ✓ | Moderate |
Lin et al. [28] | ✓ | ✓ | ✗ | ✓ | ✓ | ✓ | n/a | ✓ | ✓ | Moderate |
Meadows et al. [34] | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | n/a | ✓ | ✓ | High |
Purkey et al. [24] | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | n/a | ✓ | ✓ | High |
Radulovic et al. [29] | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | n/a | ✓ | ✓ | High |
Roder et al. [38] | ✓ | ✓ | Unclear | Unclear | ✓ | ✓ | n/a | ✓ | n/a | Low |
Sopo et al. [32] | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | n/a | ✓ | n/a | High |
Wilson et al. [31] | ✓ | ✓ | Unclear | Unclear | Unclear | ✓ | n/a | ✓ | ✓ | Low |
Zhang et al.[33] | ✓ | ✓ | ✓ | Unclear | ✓ | ✓ | n/a | ✓ | n/a | Moderate |
Study ID | SLIT | SCIT |
---|---|---|
Calderon et al. [25] | NA | +++ |
Di Bona et al. [27] | +/− | NA |
Di Bona et al. [26] | +/− | NA |
Dranitsaris et al. [37] | ++ (indirect analysis) | NA |
Dretzke et al. [36] | +++ | +++ |
Erekosima et al. [22] | NA | ++/+++ |
Feng et al. [23] | NA | – |
Kim et al. [35] | ++ | ++ |
Lin et al. [28] | ++ | NA |
Meadows et al. [34] | ++ (only in adults) | ++ (only in adults) |
Purkey et al. [24] | NA | +++ |
Radulovic et al. [29] | ++/+++ | NA |
Röder et al. [38] a
| – | – |
Sopo et al. [32] | +/++ | NA |
Wilson et al. [31] | ++ (only in adults) | NA |
Zhang (2014) | ++ (MS)/− (SS) | NA |