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Meta-Analysis
. 2012 Oct 17;10(10):CD008838.
doi: 10.1002/14651858.CD008838.pub2.

Venom immunotherapy for preventing allergic reactions to insect stings

Robert J Boyle  1 , Mariam Elremeli, Juliet Hockenhull, Mary Gemma Cherry, Max K Bulsara, Michael Daniels, J N G Oude Elberink
Affiliations
Meta-Analysis

Venom immunotherapy for preventing allergic reactions to insect stings

Robert J Boyle et al. Cochrane Database Syst Rev. .

Abstract

Background: Venom immunotherapy (VIT) is commonly used for preventing further allergic reactions to insect stings in people who have had a sting reaction. The efficacy and safety of this treatment has not previously been assessed by a high-quality systematic review.

Objectives: To assess the effects of immunotherapy using extracted insect venom for preventing further allergic reactions to insect stings in people who have had an allergic reaction to a sting.

Search methods: We searched the following databases up to February 2012: the Cochrane Skin Group Specialised Register, CENTRAL in The Cochrane Library, MEDLINE (from 1946), EMBASE (from 1974), PsycINFO (from 1806), AMED (from 1985), LILACS (from 1982), the Armed Forces Pest Management Board Literature Retrieval System, and OpenGrey. There were no language or publication status restrictions to our searches. We searched trials databases, abstracts from recent European and North American allergy meetings, and the references of identified review articles in order to identify further relevant trials.

Selection criteria: Randomised controlled trials of venom immunotherapy using standardised venom extract in insect sting allergy.

Data collection and analysis: Two authors independently undertook study selection, data extraction, and assessment of risk of bias. We identified adverse events from included controlled trials and from a separate analysis of observational studies identified as part of a National Institute for Health and Clinical Excellence Health Technology Assessment.

Main results: We identified 6 randomised controlled trials and 1 quasi-randomised controlled trial for inclusion in the review; the total number of participants was 392. The trials had some risk of bias because five of the trials did not blind outcome assessors to treatment allocation. The interventions included ant, bee, and wasp immunotherapy in children or adults with previous systemic or large local reactions to a sting, using sublingual (one trial) or subcutaneous (six trials) VIT. We found that VIT is effective for preventing systemic allergic reaction to an insect sting, which was our primary outcome measure. This applies whether the sting occurs accidentally or is given intentionally as part of a trial procedure.In the trials, 3/113 (2.7%) participants treated with VIT had a subsequent systemic allergic reaction to a sting, compared with 37/93 (39.8%) untreated participants (risk ratio [RR] 0.10, 95% confidence interval [CI] 0.03 to 0.28). The efficacy of VIT was similar across studies; we were unable to identify a patient group or mode of treatment with different efficacy, although these analyses were limited by small numbers. We were unable to confirm whether VIT prevents fatal reactions to insect stings, because of the rarity of this outcome.Venom immunotherapy was also effective for preventing large local reactions to a sting (5 studies; 112 follow-up stings; RR 0.41, 95% CI 0.24 to 0.69) and for improving quality of life (mean difference [MD] in favour of VIT 1.21 points on a 7-point scale, 95% CI 0.75 to 1.67).We found a significant risk of systemic adverse reaction to VIT treatment: 6 trials reported this outcome, in which 14 of 150 (9.3%) participants treated with VIT and 1 of 135 (0.7%) participants treated with placebo or no treatment suffered a systemic reaction to treatment (RR 8.16, 95% CI 1.53 to 43.46; 2 studies contributed to the effect estimate). Our analysis of 11 observational studies found systemic adverse reactions occurred in 131/921 (14.2%) participants treated with bee venom VIT and 8/289 (2.8%) treated with wasp venom VIT.

Authors' conclusions: We found venom immunotherapy using extracted insect venom to be an effective therapy for preventing further allergic reactions to insect stings, which can improve quality of life. The treatment carries a small but significant risk of systemic adverse reaction.

PubMed Disclaimer

Conflict of interest statement

Robert Boyle has received research funding from Lincoln Medical Ltd and support for conference attendance from Meda Pharmaceuticals, both of which market adrenaline autoinjector devices, and his department has received research support from Allergy Therapeutics who market allergen immunotherapy products, including venom immunotherapy.

Hanneke Oude Elberink (J.N.G. Oude Elberink) undertook two of the trials included in this review. She has received research support from ALK‐Abello who market allergen immunotherapy, and HAL Allergy; she has received honorarium from MSD, Allergopharma, ALK‐Abello, and AstraZeneca; and she has received fees for consulting from ALK‐Abello and HAL Allergy.

Mariam Elremeli, Max Bulsara, Juliet Hockenhull, Gemma Cherry, and Michael Daniels have no interests to declare.

A clinical referee on the review, Dr Cristoforo Incorvaia, has received fees as a scientific consultant from the producer of allergen extracts, Stallergenes.

Figures

1
1
'Risk of bias' graph: review authors' judgements about each 'Risk of bias' item presented as percentages across all included studies.
2
2
'Risk of bias' summary: review authors' judgements about each 'Risk of bias' item for each included study.
1.1
1.1. Analysis
Comparison 1 Risk of systemic reaction ‐ Immunotherapy versus control, Outcome 1 Any systemic reaction to field or challenge sting.
1.2
1.2. Analysis
Comparison 1 Risk of systemic reaction ‐ Immunotherapy versus control, Outcome 2 Mild systemic reaction to field or challenge sting.
1.3
1.3. Analysis
Comparison 1 Risk of systemic reaction ‐ Immunotherapy versus control, Outcome 3 Moderate systemic reaction to field or challenge sting.
1.4
1.4. Analysis
Comparison 1 Risk of systemic reaction ‐ Immunotherapy versus control, Outcome 4 Severe systemic reaction to field or challenge sting.
1.5
1.5. Analysis
Comparison 1 Risk of systemic reaction ‐ Immunotherapy versus control, Outcome 5 Systemic reaction to field or challenge sting requiring adrenaline treatment.
2.1
2.1. Analysis
Comparison 2 Risk of systemic reaction ‐ Analysed by number treated, Outcome 1 Any systemic reaction to field or challenge sting.
3.1
3.1. Analysis
Comparison 3 Risk of local reaction ‐ Immunotherapy versus control, Outcome 1 Large local reaction to field or challenge sting.
4.1
4.1. Analysis
Comparison 4 Quality of life ‐ Immunotherapy versus control, Outcome 1 Vespid Quality of Life Questionnaire ‐ end of treatment.
4.2
4.2. Analysis
Comparison 4 Quality of life ‐ Immunotherapy versus control, Outcome 2 Vespid Quality of Life Questionnaire ‐ change during treatment.
4.3
4.3. Analysis
Comparison 4 Quality of life ‐ Immunotherapy versus control, Outcome 3 Vespid Quality of Life Questionnaire ‐ response rate.
5.1
5.1. Analysis
Comparison 5 Adverse reaction to treatment ‐ Immunotherapy versus control, Outcome 1 Any local reaction.
5.2
5.2. Analysis
Comparison 5 Adverse reaction to treatment ‐ Immunotherapy versus control, Outcome 2 Any systemic reaction.
5.3
5.3. Analysis
Comparison 5 Adverse reaction to treatment ‐ Immunotherapy versus control, Outcome 3 Number of systemic reactions per participant.
5.4
5.4. Analysis
Comparison 5 Adverse reaction to treatment ‐ Immunotherapy versus control, Outcome 4 Number of systemic reactions per visit.
5.5
5.5. Analysis
Comparison 5 Adverse reaction to treatment ‐ Immunotherapy versus control, Outcome 5 Mild systemic reaction.
5.6
5.6. Analysis
Comparison 5 Adverse reaction to treatment ‐ Immunotherapy versus control, Outcome 6 Moderate systemic reaction.
5.7
5.7. Analysis
Comparison 5 Adverse reaction to treatment ‐ Immunotherapy versus control, Outcome 7 Severe systemic reaction.
5.8
5.8. Analysis
Comparison 5 Adverse reaction to treatment ‐ Immunotherapy versus control, Outcome 8 Systemic reaction requiring adrenaline treatment.
6.1
6.1. Analysis
Comparison 6 Planned subgroup analyses ‐ Immunotherapy versus control, Outcome 1 Systemic reaction to field or challenge sting by route of immunotherapy.
6.2
6.2. Analysis
Comparison 6 Planned subgroup analyses ‐ Immunotherapy versus control, Outcome 2 Systemic reaction to field or challenge sting by age.
6.3
6.3. Analysis
Comparison 6 Planned subgroup analyses ‐ Immunotherapy versus control, Outcome 3 Systemic reaction to field or challenge sting by duration of immunotherapy.
6.4
6.4. Analysis
Comparison 6 Planned subgroup analyses ‐ Immunotherapy versus control, Outcome 4 Systemic reaction to field or challenge sting by insect species.
6.5
6.5. Analysis
Comparison 6 Planned subgroup analyses ‐ Immunotherapy versus control, Outcome 5 Systemic reaction to field or challenge sting by updosing schedule.
6.6
6.6. Analysis
Comparison 6 Planned subgroup analyses ‐ Immunotherapy versus control, Outcome 6 Systemic adverse reaction to treatment by route of immunotherapy.
6.7
6.7. Analysis
Comparison 6 Planned subgroup analyses ‐ Immunotherapy versus control, Outcome 7 Systemic adverse reaction to treatment by age.
6.8
6.8. Analysis
Comparison 6 Planned subgroup analyses ‐ Immunotherapy versus control, Outcome 8 Systemic adverse reaction to treatment by duration of immunotherapy.
6.9
6.9. Analysis
Comparison 6 Planned subgroup analyses ‐ Immunotherapy versus control, Outcome 9 Systemic adverse reaction to treatment by insect species.
6.10
6.10. Analysis
Comparison 6 Planned subgroup analyses ‐ Immunotherapy versus control, Outcome 10 Systemic adverse reaction to treatment by updosing schedule.
7.1
7.1. Analysis
Comparison 7 Unplanned subgroup analyses ‐ Immunotherapy versus control, Outcome 1 Systemic reaction to field or challenge sting by history of prior systemic reaction.
7.2
7.2. Analysis
Comparison 7 Unplanned subgroup analyses ‐ Immunotherapy versus control, Outcome 2 Systemic adverse reaction to treatment by history of prior systemic reaction.
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Update of

  • doi: 10.1002/14651858.CD008838

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