Previous reaction severity associated with epinephrine use in home oral immunotherapy
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The severity of previous reactions can predict the potential need for epinephrine treatment during home administration of OIT for food allergy, according to a study published in Annals of Allergy, Asthma & Immunology.
However, most patients who experienced these reactions also achieved desensitization, Liat Nachshon, MD, fellow at the Institute of Allergy, Immunology and Pediatric Pulmonology at the Yitzhak Shamir Medical Center in Zerifin, Israel, and colleagues wrote.
The study comprised 642 patients (median age, 6.8 years; range, 3.7-35.6; 61.9% male) who received 756 OIT treatments for peanut (45.8%), tree nut (29.1%), sesame (15.2%) or egg (9.9%) allergy between April 2010 and January 2020, with full or partial desensitization or failure of treatment by December 2021.
Of the patients, 88 (13.7%) patients were treated for two allergens, 12 (1.9%) were treated for three allergens and one patient had four consecutive OIT treatments.
Treatment began in clinic to determine the patients’ single highest-tolerated dose (SHTD) of their allergen. Patients then consumed the SHTD at home each day for 24 days, followed by the next up-dosing visit. Treatment aimed to achieve desensitization to a specified maintenance dose based on the allergen.
Patients sent daily reports about their treatment at home via a web-based system. They also were instructed to use epinephrine autoinjectors in response to severe reactions —including severe abdominal pain, significant shortness of breath or lethargy or whenever they were in doubt — and to seek emergency care whenever epinephrine was used, providing detailed reports regarding the reaction.
The median duration for up-dosing was 9.6 months (interquartile range, 4.7-14.5). Overall, 656 (86.7%) treatments achieved full desensitization, 64 (8.4%) achieved partial desensitization and 37 (4.9%) failed.
Also, epinephrine treatment was required for 107 patients (14.2%) during clinic up-dosing and 83 (11%) patients during home administration, the latter of which were for tree nut (16.8%), peanut (9.8%), sesame (6.1%) and egg (6.7%).
More than 50% of the home epinephrine-treated reactions (HETRs) followed protein doses of less than 300 mg. Identified triggers included physical exercise (19%), fatigue (12%) and concurrent illness (10%), with 34% having no identifiable trigger other than the treatment dose.
Approximately 85% of these reactions involved respiratory symptoms, and approximately 70% of them probably met the criteria for anaphylactic reactions, the researchers wrote, validating the need for epinephrine.
Risk factors for HETRs included older age (P = .0426); a history of anaphylactic reactions, defined as reactions involving two or more organ systems or requiring treatment with epinephrine or in the ED before OIT (P < .001); a low SHTD at the start of OIT (P = .0002); and reactions treated with epinephrine during in-clinic inductions (P < .0001).
Patients treated for tree nuts experienced a higher rate of HETRs than those treated for peanuts (P = .0144), with higher rates observed for those treated for walnuts (20.4%) or hazelnuts (25%) compared with cashews (5.3%; P = .006).
Based on multivariable Cox regression analysis, the risk factors for HETRs included a previous epinephrine-treated reaction (P = .002) and epinephrine treatment during induction (P = .0011) for peanut OIT, and epinephrine-treated reaction during induction (P = .0003) for tree nut OIT.
Among patients who did not experience any HETRs, 88.3% achieved full desensitization, 7.3% achieved partial desensitization and 4.4% failed. Failure rates ranged from 1% for sesame to 8.6% for egg.
Patients who did experience HETRs showed a significantly lower full desensitization rate at 73.6% (P = .001), but failure rates in this group remained low at 8.4%, the researchers continued, including no failures for sesame or cashew and 20% for egg.
According to the researchers, these findings could help clinicians identify high-risk patients and direct them to adjusted protocols, improving the safety of OIT. These various risks also could indicate potential cofactors for adverse reactions to different foods, the researchers continued, meriting further study.
Perspective
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This study explored risk factors for the buildup phase of OIT regarding home reactions requiring epinephrine administration. The authors retrospectively analyzed their data of patients receiving OIT, finding that previous reaction severity was the main predictor for HETRs during OIT. Furthermore, such reactions were more frequent during walnut and hazelnut OIT compared with other foods studied. It is interesting to note that most patients who experienced HETRs were able to achieve desensitization.
Multiple studies have demonstrated that prior severe reaction is a risk for future severe reactions. As to specific foods resulting in HETR, this is evolving literature, and this study provides some direction.
Lastly, it is encouraging that even those with HETR can achieve desensitization. This indicates that OIT is not without potential side effects, but for those willing to take the risk, it may lead to a wonderful outcome.
Presently, the only OIT approved in the United States is for peanuts. Thus, literature such as the study seen here may help us for future expansion. Researchers need to continue data mining from centers that provide OIT to disparate foods.
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