Allergen immunotherapy for IgE-mediated food allergy: A systematic review and meta-analysis

Ulugbek Nurmatov, S Dhami, S. Arasi, Giovanni Battista Pajno, Monserrat Fernandez-Rivas, A Muraro, G Roberts, C Akdis, Montserrat Alvaro-Lozano, K Beyer, C. Bindslev-Jensen, Wesley Burks, G Du Toit, M. Ebisawa, P. Eigenmann, Edward Knol, Mika Makela, Kari Christine Nadeau, L O'Mahony, N PapadopoulosL. K. Poulsen, Cansin Sackesen, H. Sampson, A F Santos, Ronald van Ree, F Timmermans, A Sheikh

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Abstract

Background: The European Academy of Allergy and Clinical Immunology (EAACI) is developing Guidelines for Allergen Immunotherapy (AIT) for IgE-mediated Food Allergy. To inform the development of clinical recommendations, we sought to critically assess evidence on the effectiveness, safety and cost-effectiveness of AIT in the management of food allergy. Methods: We undertook a systematic review and meta-analysis that involved searching nine international electronic databases for randomized controlled trials (RCTs) and nonrandomized studies (NRS). Eligible studies were independently assessed by two reviewers against predefined eligibility criteria. The quality of studies was assessed using the Cochrane Risk of Bias tool for RCTs and the Cochrane ACROBAT-NRS tool for quasi-RCTs. Random-effects meta-analyses were undertaken, with planned subgroup and sensitivity analyses. Results: We identified 1814 potentially relevant papers from which we selected 31 eligible studies, comprising of 25 RCTs and six NRS, studying a total of 1259 patients. Twenty-five trials evaluated oral immunotherapy (OIT), five studies investigated sublingual immunotherapy, and one study evaluated epicutaneous immunotherapy. The majority of these studies were in children. Twenty-seven studies assessed desensitization, and eight studies investigated sustained unresponsiveness postdiscontinuation of AIT. Meta-analyses demonstrated a substantial benefit in terms of desensitization (risk ratio (RR) = 0.16, 95% CI 0.10, 0.26) and suggested, but did not confirm sustained unresponsiveness (RR = 0.29, 95% CI 0.08, 1.13). Only one study reported on disease-specific quality of life (QoL), which reported no comparative results between OIT and control group. Meta-analyses revealed that the risk of experiencing a systemic adverse reaction was higher in those receiving AIT, with a more marked increase in the risk of local adverse reactions. Sensitivity analysis excluding those studies judged to be at high risk of bias demonstrated the robustness of summary estimates of effectiveness and safety of AIT for food allergy. None of the studies reported data on health economic analyses. Conclusions: AIT may be effective in raising the threshold of reactivity to a range of foods in children with IgE-mediated food allergy whilst receiving (i.e. desensitization) and post-discontinuation of AIT. It is, however, associated with a modest increased risk in serious systemic adverse reactions and a substantial increase in minor local adverse reactions. More data are needed in relation to adults, long term effects, the impact on QoL and the cost-effectiveness of AIT.

Original languageEnglish
JournalAllergy: European Journal of Allergy and Clinical Immunology
Volume72
Issue number8
Pages (from-to)1133–1147
ISSN0105-4538
DOIs
Publication statusPublished - Aug 2017

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Food Hypersensitivity
Meta-Analysis
Randomized Controlled Trials
Cost-Benefit Analysis
Odds Ratio
Quality of Life
Sublingual Immunotherapy
Safety
Allergy and Immunology
Databases
Guidelines
Food
Control Groups
Health

Keywords

  • Allergen immunotherapy
  • Desensitization
  • Food allergy
  • Safety
  • Sustained unresponsiveness
  • Food Hypersensitivity/immunology
  • Humans
  • Treatment Outcome
  • Desensitization, Immunologic/methods
  • Sublingual Immunotherapy
  • Allergens/administration & dosage
  • Food/adverse effects
  • Immunoglobulin E/immunology
  • Animals
  • Quality of Life
  • Odds Ratio

Cite this

Nurmatov, U., Dhami, S., Arasi, S., Pajno, G. B., Fernandez-Rivas, M., Muraro, A., ... Sheikh, A. (2017). Allergen immunotherapy for IgE-mediated food allergy: A systematic review and meta-analysis. Allergy: European Journal of Allergy and Clinical Immunology, 72(8), 1133–1147. https://doi.org/10.1111/all.13124
Nurmatov, Ulugbek ; Dhami, S ; Arasi, S. ; Pajno, Giovanni Battista ; Fernandez-Rivas, Monserrat ; Muraro, A ; Roberts, G ; Akdis, C ; Alvaro-Lozano, Montserrat ; Beyer, K ; Bindslev-Jensen, C. ; Burks, Wesley ; Du Toit, G ; Ebisawa, M. ; Eigenmann, P. ; Knol, Edward ; Makela, Mika ; Nadeau, Kari Christine ; O'Mahony, L ; Papadopoulos, N ; Poulsen, L. K. ; Sackesen, Cansin ; Sampson, H. ; Santos, A F ; van Ree, Ronald ; Timmermans, F ; Sheikh, A. / Allergen immunotherapy for IgE-mediated food allergy : A systematic review and meta-analysis. In: Allergy: European Journal of Allergy and Clinical Immunology. 2017 ; Vol. 72, No. 8. pp. 1133–1147.
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abstract = "Background: The European Academy of Allergy and Clinical Immunology (EAACI) is developing Guidelines for Allergen Immunotherapy (AIT) for IgE-mediated Food Allergy. To inform the development of clinical recommendations, we sought to critically assess evidence on the effectiveness, safety and cost-effectiveness of AIT in the management of food allergy. Methods: We undertook a systematic review and meta-analysis that involved searching nine international electronic databases for randomized controlled trials (RCTs) and nonrandomized studies (NRS). Eligible studies were independently assessed by two reviewers against predefined eligibility criteria. The quality of studies was assessed using the Cochrane Risk of Bias tool for RCTs and the Cochrane ACROBAT-NRS tool for quasi-RCTs. Random-effects meta-analyses were undertaken, with planned subgroup and sensitivity analyses. Results: We identified 1814 potentially relevant papers from which we selected 31 eligible studies, comprising of 25 RCTs and six NRS, studying a total of 1259 patients. Twenty-five trials evaluated oral immunotherapy (OIT), five studies investigated sublingual immunotherapy, and one study evaluated epicutaneous immunotherapy. The majority of these studies were in children. Twenty-seven studies assessed desensitization, and eight studies investigated sustained unresponsiveness postdiscontinuation of AIT. Meta-analyses demonstrated a substantial benefit in terms of desensitization (risk ratio (RR) = 0.16, 95{\%} CI 0.10, 0.26) and suggested, but did not confirm sustained unresponsiveness (RR = 0.29, 95{\%} CI 0.08, 1.13). Only one study reported on disease-specific quality of life (QoL), which reported no comparative results between OIT and control group. Meta-analyses revealed that the risk of experiencing a systemic adverse reaction was higher in those receiving AIT, with a more marked increase in the risk of local adverse reactions. Sensitivity analysis excluding those studies judged to be at high risk of bias demonstrated the robustness of summary estimates of effectiveness and safety of AIT for food allergy. None of the studies reported data on health economic analyses. Conclusions: AIT may be effective in raising the threshold of reactivity to a range of foods in children with IgE-mediated food allergy whilst receiving (i.e. desensitization) and post-discontinuation of AIT. It is, however, associated with a modest increased risk in serious systemic adverse reactions and a substantial increase in minor local adverse reactions. More data are needed in relation to adults, long term effects, the impact on QoL and the cost-effectiveness of AIT.",
keywords = "Allergen immunotherapy, Desensitization, Food allergy, Safety, Sustained unresponsiveness, Food Hypersensitivity/immunology, Humans, Treatment Outcome, Desensitization, Immunologic/methods, Sublingual Immunotherapy, Allergens/administration & dosage, Food/adverse effects, Immunoglobulin E/immunology, Animals, Quality of Life, Odds Ratio",
author = "Ulugbek Nurmatov and S Dhami and S. Arasi and Pajno, {Giovanni Battista} and Monserrat Fernandez-Rivas and A Muraro and G Roberts and C Akdis and Montserrat Alvaro-Lozano and K Beyer and C. Bindslev-Jensen and Wesley Burks and {Du Toit}, G and M. Ebisawa and P. Eigenmann and Edward Knol and Mika Makela and Nadeau, {Kari Christine} and L O'Mahony and N Papadopoulos and Poulsen, {L. K.} and Cansin Sackesen and H. Sampson and Santos, {A F} and {van Ree}, Ronald and F Timmermans and A Sheikh",
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month = "8",
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language = "English",
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journal = "Allergy: European Journal of Allergy and Clinical Immunology",
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Nurmatov, U, Dhami, S, Arasi, S, Pajno, GB, Fernandez-Rivas, M, Muraro, A, Roberts, G, Akdis, C, Alvaro-Lozano, M, Beyer, K, Bindslev-Jensen, C, Burks, W, Du Toit, G, Ebisawa, M, Eigenmann, P, Knol, E, Makela, M, Nadeau, KC, O'Mahony, L, Papadopoulos, N, Poulsen, LK, Sackesen, C, Sampson, H, Santos, AF, van Ree, R, Timmermans, F & Sheikh, A 2017, 'Allergen immunotherapy for IgE-mediated food allergy: A systematic review and meta-analysis', Allergy: European Journal of Allergy and Clinical Immunology, vol. 72, no. 8, pp. 1133–1147. https://doi.org/10.1111/all.13124

Allergen immunotherapy for IgE-mediated food allergy : A systematic review and meta-analysis. / Nurmatov, Ulugbek; Dhami, S; Arasi, S.; Pajno, Giovanni Battista; Fernandez-Rivas, Monserrat; Muraro, A; Roberts, G; Akdis, C ; Alvaro-Lozano, Montserrat; Beyer, K; Bindslev-Jensen, C.; Burks, Wesley; Du Toit, G; Ebisawa, M.; Eigenmann, P.; Knol, Edward; Makela, Mika; Nadeau, Kari Christine; O'Mahony, L; Papadopoulos, N; Poulsen, L. K.; Sackesen, Cansin; Sampson, H.; Santos, A F; van Ree, Ronald; Timmermans, F; Sheikh, A.

In: Allergy: European Journal of Allergy and Clinical Immunology, Vol. 72, No. 8, 08.2017, p. 1133–1147.

Research output: Contribution to journalReviewResearchpeer-review

TY - JOUR

T1 - Allergen immunotherapy for IgE-mediated food allergy

T2 - A systematic review and meta-analysis

AU - Nurmatov, Ulugbek

AU - Dhami, S

AU - Arasi, S.

AU - Pajno, Giovanni Battista

AU - Fernandez-Rivas, Monserrat

AU - Muraro, A

AU - Roberts, G

AU - Akdis, C

AU - Alvaro-Lozano, Montserrat

AU - Beyer, K

AU - Bindslev-Jensen, C.

AU - Burks, Wesley

AU - Du Toit, G

AU - Ebisawa, M.

AU - Eigenmann, P.

AU - Knol, Edward

AU - Makela, Mika

AU - Nadeau, Kari Christine

AU - O'Mahony, L

AU - Papadopoulos, N

AU - Poulsen, L. K.

AU - Sackesen, Cansin

AU - Sampson, H.

AU - Santos, A F

AU - van Ree, Ronald

AU - Timmermans, F

AU - Sheikh, A

PY - 2017/8

Y1 - 2017/8

N2 - Background: The European Academy of Allergy and Clinical Immunology (EAACI) is developing Guidelines for Allergen Immunotherapy (AIT) for IgE-mediated Food Allergy. To inform the development of clinical recommendations, we sought to critically assess evidence on the effectiveness, safety and cost-effectiveness of AIT in the management of food allergy. Methods: We undertook a systematic review and meta-analysis that involved searching nine international electronic databases for randomized controlled trials (RCTs) and nonrandomized studies (NRS). Eligible studies were independently assessed by two reviewers against predefined eligibility criteria. The quality of studies was assessed using the Cochrane Risk of Bias tool for RCTs and the Cochrane ACROBAT-NRS tool for quasi-RCTs. Random-effects meta-analyses were undertaken, with planned subgroup and sensitivity analyses. Results: We identified 1814 potentially relevant papers from which we selected 31 eligible studies, comprising of 25 RCTs and six NRS, studying a total of 1259 patients. Twenty-five trials evaluated oral immunotherapy (OIT), five studies investigated sublingual immunotherapy, and one study evaluated epicutaneous immunotherapy. The majority of these studies were in children. Twenty-seven studies assessed desensitization, and eight studies investigated sustained unresponsiveness postdiscontinuation of AIT. Meta-analyses demonstrated a substantial benefit in terms of desensitization (risk ratio (RR) = 0.16, 95% CI 0.10, 0.26) and suggested, but did not confirm sustained unresponsiveness (RR = 0.29, 95% CI 0.08, 1.13). Only one study reported on disease-specific quality of life (QoL), which reported no comparative results between OIT and control group. Meta-analyses revealed that the risk of experiencing a systemic adverse reaction was higher in those receiving AIT, with a more marked increase in the risk of local adverse reactions. Sensitivity analysis excluding those studies judged to be at high risk of bias demonstrated the robustness of summary estimates of effectiveness and safety of AIT for food allergy. None of the studies reported data on health economic analyses. Conclusions: AIT may be effective in raising the threshold of reactivity to a range of foods in children with IgE-mediated food allergy whilst receiving (i.e. desensitization) and post-discontinuation of AIT. It is, however, associated with a modest increased risk in serious systemic adverse reactions and a substantial increase in minor local adverse reactions. More data are needed in relation to adults, long term effects, the impact on QoL and the cost-effectiveness of AIT.

AB - Background: The European Academy of Allergy and Clinical Immunology (EAACI) is developing Guidelines for Allergen Immunotherapy (AIT) for IgE-mediated Food Allergy. To inform the development of clinical recommendations, we sought to critically assess evidence on the effectiveness, safety and cost-effectiveness of AIT in the management of food allergy. Methods: We undertook a systematic review and meta-analysis that involved searching nine international electronic databases for randomized controlled trials (RCTs) and nonrandomized studies (NRS). Eligible studies were independently assessed by two reviewers against predefined eligibility criteria. The quality of studies was assessed using the Cochrane Risk of Bias tool for RCTs and the Cochrane ACROBAT-NRS tool for quasi-RCTs. Random-effects meta-analyses were undertaken, with planned subgroup and sensitivity analyses. Results: We identified 1814 potentially relevant papers from which we selected 31 eligible studies, comprising of 25 RCTs and six NRS, studying a total of 1259 patients. Twenty-five trials evaluated oral immunotherapy (OIT), five studies investigated sublingual immunotherapy, and one study evaluated epicutaneous immunotherapy. The majority of these studies were in children. Twenty-seven studies assessed desensitization, and eight studies investigated sustained unresponsiveness postdiscontinuation of AIT. Meta-analyses demonstrated a substantial benefit in terms of desensitization (risk ratio (RR) = 0.16, 95% CI 0.10, 0.26) and suggested, but did not confirm sustained unresponsiveness (RR = 0.29, 95% CI 0.08, 1.13). Only one study reported on disease-specific quality of life (QoL), which reported no comparative results between OIT and control group. Meta-analyses revealed that the risk of experiencing a systemic adverse reaction was higher in those receiving AIT, with a more marked increase in the risk of local adverse reactions. Sensitivity analysis excluding those studies judged to be at high risk of bias demonstrated the robustness of summary estimates of effectiveness and safety of AIT for food allergy. None of the studies reported data on health economic analyses. Conclusions: AIT may be effective in raising the threshold of reactivity to a range of foods in children with IgE-mediated food allergy whilst receiving (i.e. desensitization) and post-discontinuation of AIT. It is, however, associated with a modest increased risk in serious systemic adverse reactions and a substantial increase in minor local adverse reactions. More data are needed in relation to adults, long term effects, the impact on QoL and the cost-effectiveness of AIT.

KW - Allergen immunotherapy

KW - Desensitization

KW - Food allergy

KW - Safety

KW - Sustained unresponsiveness

KW - Food Hypersensitivity/immunology

KW - Humans

KW - Treatment Outcome

KW - Desensitization, Immunologic/methods

KW - Sublingual Immunotherapy

KW - Allergens/administration & dosage

KW - Food/adverse effects

KW - Immunoglobulin E/immunology

KW - Animals

KW - Quality of Life

KW - Odds Ratio

U2 - 10.1111/all.13124

DO - 10.1111/all.13124

M3 - Review

C2 - 28058751

AN - SCOPUS:85017353891

VL - 72

SP - 1133

EP - 1147

JO - Allergy: European Journal of Allergy and Clinical Immunology

JF - Allergy: European Journal of Allergy and Clinical Immunology

SN - 0105-4538

IS - 8

ER -