World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) guideline update – XIII – Oral immunotherapy for CMA – Systematic review

Antonio Bognanni, MD; Derek K. Chu, MD; Ramon T. Firmino, DDS, PhD; Stefania Arasi, PhD, MSc; Siw Waffenschmidt; Arnav Agarwal, MD; Piotr Dziechciarz, MD, PhD; Andrea Horvath, MD, PhD; Rime Jebai, MSc, MPH; Hanako Mihara, MD, MPH; Yetiani Roldan, MD; Maria Said, RN; Raanan Shamir, MD, PhD; Martin Bozzola, MD; Sami Bahna, MD, DrPH; Alessandro Fiocchi, MD; Susan Waserman, MD, MSc; Holger J. Schünemann, MD, MSc, PhD; Jan L. Brożek, MD, PhD; Ignacio J. Ansotegui, MD, PhD; Stefania Arasi, MD, PhD; Amal H. Assa'ad, MD; Sami L. Bahna, MD, DrPH; Roberto Berni Canani, MD, PhD; Antonio Bognanni, MD; Martin Bozzola, MD; Jan Brozek, MD, PhD; Derek K. Chu, MD, PhD; Lamia Dahdah, MD; Christophe Dupont, MD, PhD; Motohiro Ebisawa, MD, PhD; Alessandro Fiocchi, MD; Ramon Targino Firmino, MD; Elena Galli, MD, PhD; Rose Kamenwa, MD; Gideon Lack, MBBCh; Haiqi Li, MD; Alberto Martelli, MD; Anna H. Nowak-Wegrzyn, MD, PhD; Nikolaos G. Papadopoulos, MD, PhD; Ruby Pawankar, MD, PhD; Maria Said, RN; Mario Sánchez-Borges, MD; Holger J. Schünemann, MD, MSc, PhD; Raanan Shamir, MD, PhD; Jonathan M. Spergel, MD, PhD; Hania Szajewska, MD; Luigi Terracciano, MD; Yvan Vandenplas, MD, PhD; Carina Venter, PhD, RD; Amena Warner, RN, SN (PG Dip); Susan Waserman, MD, MSc; GaryW.K. Wong, MD

World Allergy Organization Journal (Sep 2022)

World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) guideline update – XIII – Oral immunotherapy for CMA – Systematic review

Antonio Bognanni, MD,
Derek K. Chu, MD,
Ramon T. Firmino, DDS, PhD,
Stefania Arasi, PhD, MSc,
Siw Waffenschmidt,
Arnav Agarwal, MD,
Piotr Dziechciarz, MD, PhD,
Andrea Horvath, MD, PhD,
Rime Jebai, MSc, MPH,
Hanako Mihara, MD, MPH,
Yetiani Roldan, MD,
Maria Said, RN,
Raanan Shamir, MD, PhD,
Martin Bozzola, MD,
Sami Bahna, MD, DrPH,
Alessandro Fiocchi, MD,
Susan Waserman, MD, MSc,
Holger J. Schünemann, MD, MSc, PhD,
Jan L. Brożek, MD, PhD,
Ignacio J. Ansotegui, MD, PhD,
Stefania Arasi, MD, PhD,
Amal H. Assa'ad, MD,
Sami L. Bahna, MD, DrPH,
Roberto Berni Canani, MD, PhD,
Antonio Bognanni, MD,
Martin Bozzola, MD,
Jan Brozek, MD, PhD,
Derek K. Chu, MD, PhD,
Lamia Dahdah, MD,
Christophe Dupont, MD, PhD,
Motohiro Ebisawa, MD, PhD,
Alessandro Fiocchi, MD,
Ramon Targino Firmino, MD,
Elena Galli, MD, PhD,
Rose Kamenwa, MD,
Gideon Lack, MBBCh,
Haiqi Li, MD,
Alberto Martelli, MD,
Anna H. Nowak-Wegrzyn, MD, PhD,
Nikolaos G. Papadopoulos, MD, PhD,
Ruby Pawankar, MD, PhD,
Maria Said, RN,
Mario Sánchez-Borges, MD,
Holger J. Schünemann, MD, MSc, PhD,
Raanan Shamir, MD, PhD,
Jonathan M. Spergel, MD, PhD,
Hania Szajewska, MD,
Luigi Terracciano, MD,
Yvan Vandenplas, MD, PhD,
Carina Venter, PhD, RD,
Amena Warner, RN, SN (PG Dip),
Susan Waserman, MD, MSc,
GaryW.K. Wong, MD

Affiliations

Antonio Bognanni, MD: Department of Health Research Methods, Evidence & Impact, McMaster University, Hamilton, Ontario, Canada
Derek K. Chu, MD: Department of Medicine, Department of Health Research Methods, Evidence & Impact, Division of Clinical Immunology and Allergy, McMaster University, Hamilton, Ontario, Canada
Ramon T. Firmino, DDS, PhD: Department of Pediatric Dentistry, Faculty of Dentistry, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil; Faculty of Medical Sciences of Campina Grande, UNIFACISA University Center, Campina Grande, Paraiba, Brazil
Stefania Arasi, PhD, MSc: Translational Research in Pediatric Specialities Area, Division of Allergy, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
Siw Waffenschmidt: Institute for Quality and Efficiency in Health Care, Cologne, Germany
Arnav Agarwal, MD: Division of General Internal Medicine, Department of Medicine, McMaster University, Hamilton, Ontario, Canada
Piotr Dziechciarz, MD, PhD: Medical University of Warsaw, Warsaw, Poland
Andrea Horvath, MD, PhD: Medical University of Warsaw, Warsaw, Poland
Rime Jebai, MSc, MPH: Department of Epidemiology, Robert Stempel College of Public Health, Florida International University, 11200 SW 8th St, Miami, FL 33199, USA
Hanako Mihara, MD, MPH: Nippon Boehringer Ingelheim, Japan
Yetiani Roldan, MD: McMaster University, Hamilton, Ontario, Canada
Maria Said, RN: CEO Allergy & Anaphylaxis Australia, Sydney, Australia
Raanan Shamir, MD, PhD: Institute for Gastroenterology, Nutrition and Liver Diseases, Schneider Children's Medical Center of Israel, Sackler Faculty of Medicine, Tel Aviv University, Israel
Martin Bozzola, MD: Pediatric Allergy and Immunology Section, Department of Pediatrics, Hospital Británico de Buenos Aires, Argentina
Sami Bahna, MD, DrPH: Louisiana State University Health Sciences Center, Shreveport, Louisiana, USA
Alessandro Fiocchi, MD: Translational Research in Pediatric Specialities Area, Division of Allergy, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
Susan Waserman, MD, MSc: Department of Medicine, Division of Clinical Immunology and Allergy, McMaster University, Hamilton, Ontario, Canada
Holger J. Schünemann, MD, MSc, PhD: Department of Health Research Methods, Evidence & Impact and Department of Medicine, Division of Internal Medicine, McMaster University, Hamilton, Ontario, Canada
Jan L. Brożek, MD, PhD: Department of Health Research Methods, Evidence & Impact and Department of Medicine, Division of Clinical Immunology and Allergy, McMaster University, Hamilton, Ontario, Canada; Corresponding author. Jan L. Brożek, MD, PhD, Department of Health Research Methods, Evidence, and Impact McMaster University, Health Sciences Centre Area 2C, 1280 Main Street West, Hamilton, ON L8S 4K1, Canada.
Ignacio J. Ansotegui, MD, PhD
Stefania Arasi, MD, PhD
Amal H. Assa'ad, MD
Sami L. Bahna, MD, DrPH
Roberto Berni Canani, MD, PhD
Antonio Bognanni, MD
Martin Bozzola, MD
Jan Brozek, MD, PhD
Derek K. Chu, MD, PhD
Lamia Dahdah, MD
Christophe Dupont, MD, PhD
Motohiro Ebisawa, MD, PhD
Alessandro Fiocchi, MD
Ramon Targino Firmino, MD
Elena Galli, MD, PhD
Rose Kamenwa, MD
Gideon Lack, MBBCh
Haiqi Li, MD
Alberto Martelli, MD
Anna H. Nowak-Wegrzyn, MD, PhD
Nikolaos G. Papadopoulos, MD, PhD
Ruby Pawankar, MD, PhD
Maria Said, RN
Mario Sánchez-Borges, MD
Holger J. Schünemann, MD, MSc, PhD
Raanan Shamir, MD, PhD
Jonathan M. Spergel, MD, PhD
Hania Szajewska, MD
Luigi Terracciano, MD
Yvan Vandenplas, MD, PhD
Carina Venter, PhD, RD
Amena Warner, RN, SN (PG Dip)
Susan Waserman, MD, MSc
GaryW.K. Wong, MD

Journal volume & issue: Vol. 15, no. 9
p. 100682

Abstract

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Background: Allergy to cow's milk is the most common food allergy in infants and it is usually outgrown by 5 years of age. In some individuals it persists beyond early childhood. Oral immunotherapy (OIT, oral desensitization, specific oral tolerance induction) has been proposed as a promising therapeutic strategy for persistent IgE-mediated cow's milk allergy. We previously published the systematic review of OIT for cow's milk allergy (CMA) in 2010 as part of the World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) Guidelines. Objective: To systematically synthesize the currently available evidence about OIT for IgE-mediated CMA and to inform the updated 2022 WAO guidelines. Methods: We searched the electronic databases including PubMed, Medline, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), and the websites of selected allergy organizations. We included all studies irrespective of the language of the original publication. The last search was conducted in February 2021. We registered the protocol on Open Science Framework (10.17605/OSF.IO/AH2DT). Results: We identified 2147 unique records published between 2010 and 2021, including 13 randomized trials and 109 observational studies addressing cow's milk OIT. We found low-certainty evidence that OIT with unheated cow's milk, compared to elimination diet alone, increased the likelihood of being able to consume ≥150 ml of cow's milk in controlled settings (risk ratio (RR): 12.3, 95% CI: 5.9 to 26.0; risk difference (RD): 25 more per 100, 95% CI 11 to 56) as well as accidently ingest a small amount (≥5 ml) of cow's milk (RR: 8.7, 95% CI: 4.7 to 16.1; RD: 25 more per 100, 95% CI 12 to 50). However, 2–8 weeks after discontinuation of a successful OIT, tolerance of cow's milk persisted in only 36% (range: 20%–91%) of patients. OIT increased the frequency of anaphylaxis (rate ratio: 60.0, 95% CI 15 to 244; rate difference 5 more anaphylactic reactions per 1 person per year, 95% CI: 4 to 6; moderate evidence) and the frequency of epinephrine use (rate ratio: 35.2, 95% CI: 9 to 136.5; rate difference 268 more events per 100 person-years, 95% CI: 203 to 333; high certainty). OIT also increased the risk of gastrointestinal symptoms (RR 6.9, 95% CI 1.6–30.9; RD 28 more per 100, CI 3 to 100) and respiratory symptoms (RR 49.0, 95% CI 3.12–770.6; RD 77 more per 100, CI 62 to 92), compared with avoidance diet alone. Single-arm observational studies showed that on average 6.9% of OIT patients (95% CI: 3.8%–10%) developed eosinophilic esophagitis (very low certainty evidence). We found 1 trial and 2 small case series of OIT with baked milk. Conclusions: Moderate certainty evidence shows that OIT with unheated cow's milk in patients with IgE-mediated CMA is associated with an increased probability of being able to drink milk and, at the same time, an increased risk of serious adverse effects.

Published in World Allergy Organization Journal

ISSN: 1939-4551 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine: Immunologic diseases. Allergy
Website: https://www.sciencedirect.com/journal/world-allergy-organization-journal

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