Cow's milk oral immunotherapy in real life: 8-year long-term follow-up study

Inês Mota; Susana Piedade; Ângela Gaspar; Filipe Benito-Garcia; Graça Sampaio; Luís Miguel Borrego; Mário Morais-Almeida

doi:10.5415/apallergy.2018.8.e28

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Mota, Piedade, Gaspar, Benito-Garcia, Sampaio, Borrego, and Morais-Almeida: Cow's milk oral immunotherapy in real life: 8-year long-term follow-up study

Original Article

Asia Pac Allergy 2018;8(3):e28.

Published online: 4 July 2018

DOI: https://doi.org/10.5415/apallergy.2018.8.e28

Cow's milk oral immunotherapy in real life: 8-year long-term follow-up study

Inês Mota, Susana Piedade, Ângela Gaspar^*, Filipe Benito-Garcia, Graça Sampaio, Luís Miguel Borrego, Mário Morais-Almeida

Immunoallergy Department, CUF Descobertas Hospital, Lisbon, Portugal

^*Correspondence to Ângela Gaspar Immunoallergy Department, CUF Descobertas Hospital, R. Mário Botas, 1998-018 Lisbon, Portugal. Tel: +351-210025200 Fax: +351-210025220 E-mail: angela.gaspar@sapo.pt

Received 1 November 2017 Accepted 13 July 2018

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background

Oral immunotherapy (OIT) has been recognized as a promising treatment for severe and long-lasting cow's milk (CM) allergy. Once maintenance has been achieved, patients should maintain daily intake of CM to ensure desensitization. Clinical experience concerning long-term follow-up is scarce.

Objective

The authors aimed to assess long-term efficacy and safety of a maintenance phase of OIT in real life.

Methods

Prospective study of all children and adolescents, who underwent CM-OIT and were subsequently followed at our allergy center on maintenance dose (200 mL daily) for at least 36 months after reaching the maintenance phase (from 2009 to 2016).

Results

Forty-two patients were enrolled: 60% male, 36% with history of anaphylaxis and 57% with asthma. The median time of follow-up was 69 months (range, 39–105 months) and the median age at the last clinical evaluation was 13 years (range, 6–23 years). Regarding adherence to the protocol: 92% are on free diet (at least 200 mL of CM daily; 7-g protein); 14% had transient interruptions and 7% definitely withdrawn with loss of tolerance. During maintenance, 45% developed mild to severe allergic reactions, and 7% had more than 3 episodes. A positive correlation between the occurrence of allergic reactions and history of anaphylaxis (p < 0.001) was found. The coexistence of asthma was risk factor for the occurrence of allergic reactions during maintenance.

Conclusion

This real-life study supports long-term efficacy and safety of CM-OIT. Despite daily intake, 41% had symptoms at some moment during the complete follow-up period; a total of 33 symptomatic days in patients with mean follow-up time of 67.5 months. Clinical tolerance depends on daily intake. The protective effect reached can be lost after CM withdrawal. History of anaphylaxis was a risk factor for the occurrence of allergic reactions during the maintenance phase.

Keywords: Anaphylaxis, Cow's milk allergy, Food allergy, Oral desensitization, Oral immunotherapy, Specific oral tolerance induction

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Fig. 1.

Characterization of the adverse reactions: symptom grading. GI, gastrointestinal.

Table 1.

Dosing schedule of the induction phase of our cow's milk oral immunotherapy protocol

Variable	Session
Variable	1 (day 1)	2 (days 14 to 28)	3 (days 28 to 56)	4 (days 42 to 70)	5 (days 56 to 84)
Dose	1 Drop^2 Drops^	1 mL 5 mL	10 mL 10 mL	50 mL 50 mL	100 mL 100 mL
	3 Drops^*	5 mL	20 mL	(interval 2 hr)	(interval 2 hr)
	4 Drops^*	10 mL	20 mL	100 mL	200 mL
	0.1 mL	10 mL	50 mL
	0.2 mL
	0.5 mL
	0.5 mL
Interval between doses	1 mL	20–30 min (^* sublingual)		20–120 min
Maintenance dose (home)	0.5 to 1 mL twice daily	5 to 10 mL twice daily	20 to 50 mL twice daily	100 mL twice daily	200 mL daily (… progressive free diet)

Table 2.

Clinical characteristics of the study group (n = 42)

Characteristic	Value
Male sex	60%
Age of CMA diagnosis (mo), median (range)	4 (0.5–12)
History of anaphylaxis	36%
Atopic dermatitis	33%
Asthma	57%
Allergic rhinitis	79%
Multiple food allergy (egg, tree nuts, peanut, fish, and shellfish)	24%
CM-OIT (induction phase)
Age at CM-OIT initiation (yr), median (range)	6 (2–18)
Period until target dose (mo), mean ± SD	5.1 ± 2.7
CM-OIT (maintenance phase)
Age at beginning (yr), median (range)	6.9 (2–18)
Age at last clinical evaluation (yr), median (range)	13 (6.7–23.8)
Time of follow-up (mo), median (range)	67 (37–103)

CMA, cow's milk allergy; CM-OIT, cow's milk-oral immunotherapy; SD, standard deviation.

Table 3.

Safety of oral immunotherapy during maintenance

Allergic reaction & symptom	No.
Allergic reactions
<3 episodes	16
≥3 episodes	3
No allergic reactions	23
Symptoms
Mucocutaneous	17
Respiratory	7
Gastrointestinal	3
Systemic reactions (at least 2 systems involved)	2
Headaches	1

Table 4.

Specific IgE levels and allergic adverse reactions before and after treatment.

Patient	Mean cow's milk IgE levels (kU/L)
Patient	Before OIT	After OIT
All patients (n = 42)	13.39	4.18
Patients with adverse reactions after OIT (n = 19)	13.34	4.99
Patients without adverse reactions after OIT (n = 23)	13.43	3.47

OIT, oral immunotherapy.

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