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

Ulugbek Nurmatov; Sangeeta Dhami; Stefania Arasi; Giovanni Battista Pajno; Montserrat Fernandez-Rivas; Antonella Muraro; Graham Roberts; Cezmi Akdis; Montserrat Alvaro-Lozano; Kirsten Beyer; Carsten Bindslev-Jensen; Wesley Burks; George du Toit; Motohiro Ebisawa; Philippe Eigenmann; Edward Knol; Mika Makela; Kari Christine Nadeau; Liam O'Mahony; Nikolaos Papadopoulos; Lars K Poulsen; Cansin Sackesen; Hugh Sampson; Alexandra Santos; Ronald van Ree; Frans Timmermans; Aziz Sheikh

doi:10.1111/all.13124

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

Ulugbek Nurmatov, Sangeeta Dhami, Stefania Arasi, Giovanni Battista Pajno, Montserrat Fernandez-Rivas, Antonella Muraro, Graham Roberts, Cezmi Akdis, Montserrat Alvaro-Lozano, Kirsten Beyer, Carsten Bindslev-Jensen, Wesley Burks, George du Toit, Motohiro Ebisawa, Philippe Eigenmann, Edward Knol, Mika Makela, Kari Christine Nadeau, Liam O'Mahony, Nikolaos PapadopoulosLars K Poulsen, Cansin Sackesen, Hugh Sampson, Alexandra Santos, Ronald van Ree, Frans Timmermans, Aziz Sheikh

Department of Clinical Medicine

196 Citations (Scopus)

83 Downloads (Pure)

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 language	English
Journal	Allergy
Volume	72
Pages (from-to)	1133-1147
ISSN	0105-4538
DOIs	https://doi.org/10.1111/all.13124
Publication status	Published - Aug 2017

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Nurmatov, U., Dhami, S., Arasi, S., Pajno, G. B., 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, K. C., O'Mahony, L., ... Sheikh, A. (2017). Allergen immunotherapy for IgE-mediated food allergy: a systematic review and meta-analysis. Allergy, 72, 1133-1147. https://doi.org/10.1111/all.13124

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, A, van Ree, R, Timmermans, F & Sheikh, A 2017, 'Allergen immunotherapy for IgE-mediated food allergy: a systematic review and meta-analysis', Allergy, vol. 72, pp. 1133-1147. https://doi.org/10.1111/all.13124

@article{2b33ffcf77104a38a21a790002a64b9e,

title = "Allergen immunotherapy for IgE-mediated food allergy: a systematic review and meta-analysis",

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.",

author = "Ulugbek Nurmatov and Sangeeta Dhami and Stefania Arasi and Pajno, {Giovanni Battista} and Montserrat Fernandez-Rivas and Antonella Muraro and Graham Roberts and Cezmi Akdis and Montserrat Alvaro-Lozano and Kirsten Beyer and Carsten Bindslev-Jensen and Wesley Burks and {du Toit}, George and Motohiro Ebisawa and Philippe Eigenmann and Edward Knol and Mika Makela and Nadeau, {Kari Christine} and Liam O'Mahony and Nikolaos Papadopoulos and Poulsen, {Lars K} and Cansin Sackesen and Hugh Sampson and Alexandra Santos and {van Ree}, Ronald and Frans Timmermans and Aziz Sheikh",

year = "2017",

month = aug,

doi = "10.1111/all.13124",

language = "English",

volume = "72",

pages = "1133--1147",

journal = "Allergy: European Journal of Allergy and Clinical Immunology",

issn = "0105-4538",

publisher = "Wiley Online",

}

TY - JOUR

T1 - Allergen immunotherapy for IgE-mediated food allergy

T2 - a systematic review and meta-analysis

AU - Nurmatov, Ulugbek

AU - Dhami, Sangeeta

AU - Arasi, Stefania

AU - Pajno, Giovanni Battista

AU - Fernandez-Rivas, Montserrat

AU - Muraro, Antonella

AU - Roberts, Graham

AU - Akdis, Cezmi

AU - Alvaro-Lozano, Montserrat

AU - Beyer, Kirsten

AU - Bindslev-Jensen, Carsten

AU - Burks, Wesley

AU - du Toit, George

AU - Ebisawa, Motohiro

AU - Eigenmann, Philippe

AU - Knol, Edward

AU - Makela, Mika

AU - Nadeau, Kari Christine

AU - O'Mahony, Liam

AU - Papadopoulos, Nikolaos

AU - Poulsen, Lars K

AU - Sackesen, Cansin

AU - Sampson, Hugh

AU - Santos, Alexandra

AU - van Ree, Ronald

AU - Timmermans, Frans

AU - Sheikh, Aziz

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.

U2 - 10.1111/all.13124

DO - 10.1111/all.13124

M3 - Review

C2 - 28058751

SN - 0105-4538

VL - 72

SP - 1133

EP - 1147

JO - Allergy: European Journal of Allergy and Clinical Immunology

JF - Allergy: European Journal of Allergy and Clinical Immunology

ER -

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

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