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April 19, 2018

Wheat Desensitization Protocols

Question

Can you provide me with a protocol for wheat desensitization?

Answer

By Dana Wallace, MD and Anna Nowak-Wegrzyn, MD, PhD

There is no standardized protocol for wheat OIT. The published data on protocols for wheat allergy desensitization is very limited and the protocols vary significantly between the studies, e.g. using peanut flour versus cooked or baked wheat products. The optimal maintenance dose as well as duration of wheat OIT have not been established.

The largest study was a randomized double-blind US multi-center trial involving 48 participants (24 wheat, 24 placebo) for a total duration of 2 years. (1)Inclusion criteria included evidence of wheat sensitization (prick test or sIgE) and a positive oral food challenge (median successfully consumed dose 43 mg wheat protein [WP] (3-145 mg). The dose was escalated biweekly starting at the threshold dose but no higher than 12 mg on day 1. High gluten flour (7 gram wheat protein/1 oz of flour) was used for the desensitization. Anti-histamine pre-treatment was not used during updosing. Dose escalation was every 2 weeks) The dose was escalated to a max of 1445 mg WP by week 44 and then maintained for the remainder of the 52 weeks. At 52 weeks, patients were challenged and 52% were able to consume 4443 mg WP without reaction compared to 0% of the placebo group. At 52 weeks this lower-dose group was continued on 1445 mg WP daily for year 2 and 39% were able to consume 7443 mg WP (equal to one cup pasta). The year one placebo group were switched over to a high-dose group with biweekly escalation to 3870 mg wheat protein and maintained until the end of year 2. At 2 years 67% of the high-dose group were able to consume 4443 mg wheat protein. When the lower-dose group stopped the daily wheat protein and were retested 2 months later, only 3/23 (13%) were still able to consume 7443 g wheat protein, demonstrating a very low rate of sustained unresponsiveness. Adverse reactions were noted in 11.2% of doses of wheat OIT (compared with 6% for placebo, none being severe in placebo group). Most adverse events were minor, e.g., itchy throat, stomachache, nausea but 0.02% severe and 0.05% were treated with epinephrine. Dropouts included: placebo-2, crossover-3, low-dose 2-year group-5. The study protocol and study results will be described in more details in a future journal article, currently under development. 

In Japan 16 patients, median age 7.0 years (5.9-13.6 yrs.) participated in an open-label wheat desensitization protocol using a 5-day in-patient rush followed by prolonged gradual out-patient updosing to 5.2 grams of wheat protein. (2) Cooked udon noodles were used as the source of wheat protein. Patient were pre-medicated with loratadine and montelukast prior to desensitization and continued until the 5.2 gram target dose was reached and then discontinued.  During the rush period, there were 2 dose increases, separated by 5 hours per day. The starting rush dose was the threshold dose (approximately 0.05 gram) which was increased or decreased as tolerated, with most patients not reaching the 5.2 grams at the end of the 5 days. The at-home long term buildup phase started at the last rush dose or 0.26 gram and increased by 0.13 gram every week as tolerated until the patient reached 5.2 gram at 20 +/- weeks. The patient was then allowed to introduce wheat-containing foods into their diet, limited to 0.65 gram protein/serving. Sustained unresponsiveness at 2 weeks after reaching the 5.2 gram target dose was achieved by 11/16 patients. However, the authors did not report on a longer period of sustained responsiveness. During the rush phase 26.4% of doses resulted in symptoms, but none required epinephrine. During the long-term buildup and maintenance phase, 6.8% of doses resulted in adverse reactions and three patients required epinephrine.

In another published study 6 patients, median age was 5.5 years (range, 5-11 years), were desensitized using semolina porridge (at low doses) and semolina pasta (at higher doses) with escalation of dose occurring in the out-patient clinic 2x/week followed by daily dosing at home until the next escalation.  (3) The low-dose updosing sequence was 0.0005, 0.001, 0.01, 0.5, 1, 2, 4 gram of porridge followed by 8,16, 30, 55, 100 gram of pasta (100 gram=13 gram of wheat protein). Once patient reached 13 gram of wheat protein, the maintenance phase was started, and this dose was repeated daily for dinner using regular food. No exercise was permitted by protocol for 4 hours after ingestion. Cetirizine use throughout induction up-dosing and tapered over one week once the maintenance phase started. During up-dosing in the hospital setting, 6 mild adverse reactions (5 in one patient who discontinued therapy) occurred from 96 doses administered. One of the 6 patients experienced generalized urticaria during the maintenance phase. This was during exercise, immediately following wheat intake. The patient was treated with antihistamines and steroids successfully. With avoiding exercise following ingestion, no further reactions were reported.

There was a study of 12 patients by Rekabi, but access to this journal article is limited. (4) Other published articles have been case reports, with 1-2 cases being reported. (5)

In summary, at this time standard protocol for wheat OIT is not available. Limited evidence suggests that desensitization can be achieved in a subset of the treated patients after 12 months of OIT and sustained unresponsiveness can be achieved in a small subset after 24 months. When considering treating patients with wheat OIT, attention must be given to avoidance of exercise following dosing as well as consistent dosing with a particular form of wheat protein, e.g. flour versus pasta or bread due to significant differences in wheat protein content in these products.

Anna Nowak-Wegrzyn, MD, PhD
Professor of Pediatrics
Icahn School of Medicine at Mount Sinai
Jaffe Food Allergy Institute
New York, NY

Dana V. Wallace, MD
Associate Professor
Nova Southeastern Allopathic Medical School
Davie, Florida

References

1. Nowak-Wegrzyn AH, Wood RA, Nadeau KC, Pongracic JA, Henning A, Beyer K, et al. Randomized Placebo-Controlled Multicenter Clinical Trial of Wheat Oral Immunotherapy. Journal of Allergy and Clinical Immunology.139(2):AB378

2. Sato S, Utsunomiya T, Imai T, Yanagida N, Asaumi T, Ogura K, et al. Wheat oral immunotherapy for wheat-induced anaphylaxis. J Allergy Clin Immunol. 2015;136(4):1131-3 e7

3. Rodriguez del Rio P, Diaz-Perales A, Sanchez-Garcia S, Escudero C, do Santos P, Catarino M, et al. Oral immunotherapy in children with IgE-mediated wheat allergy: outcome and molecular changes. J Investig Allergol Clin Immunol. 2014;24(4):240-8

4. Rekabi M, Arshi S, Bemanian MH, Rekabi V, Rajabi A, Fallahpour M, et al. Evaluation of a new protocol for wheat desensitization in patients with wheat-induced anaphylaxis. Immunotherapy. 2017;9(8):637-45

5. Pacharn P, Siripipattanamongkol N, Veskitkul J, Jirapongsananuruk O, Visitsunthorn N, Vichyanond P. Successful wheat-specific oral immunotherapy in highly sensitive individuals with a novel multirush/maintenance regimen. Asia Pac Allergy. 2014;4(3):180-3


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