Anaphylaxis occurs during up-dosing, maintenance stages of peanut oral immunotherapy
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Children and adolescents on peanut OIT may experience anaphylaxis during the up-dosing and maintenance stages, often caused by avoidable triggers, according to a study published in Pediatric Allergy and Immunology.
Better education can play a role in mitigating these events in the long term, Aikaterini (Katherine) Anagnostou, MD, MSc, PhD, FACAAI, director of the food immunotherapy and food challenge programs at Texas Children’s Hospital, and colleagues wrote.
“Food OIT is a long-term therapy, but most studies focus on short-term outcomes,” Anagnostou told Healio.
“We believe more research is required to examine the long-term effects of this therapy, including efficacy, safety and patient outcomes. These are the main reasons we focused on longer-term maintenance,” she continued.
Researchers followed 75 patients aged 3 to 17 years who reached a maintenance dose of 300 mg of peanut protein through monthly escalation for approximately 9 months following a starting dose of 2 mg. Maintenance lasted a median 25 months (range, 8-42), during which time 15 patients (20%) increased their doses to 450 mg to 900 mg, whereas three reduced their dose to 150 mg due to anaphylaxis (n = 2) or personal preference (n = 1).
Patients received education on the effects of external factors on dose thresholds, including to avoid exercise and hot showers for 2 hours after each dose, avoid dosing on an empty stomach and to stop or reduce dosing during viral illnesses.
Four patients stopped therapy due to symptoms resembling but ultimately testing negative for eosinophilic esophagitis (n = 1), aversion to the taste (n = 2) and anaphylaxis during the up-dosing phase (n = 1), with another patient lost after moving out of state.
Thirteen (17%) patients experienced 15 anaphylactic episodes during treatment, eight of which occurred during up-dosing and seven during maintenance. The latest episode of anaphylaxis occurred at 16 months. The researchers classified all the anaphylaxis episodes as grade 3, based on NIAID criteria.
During up-dosing, anaphylaxis followed 300 mg (n = 1), 150 mg (n = 3), 100 mg (n = 1), 50 mg (n = 2) and 5 mg (n = 1) doses. Anaphylaxis during maintenance followed doses of 300 mg (n = 5), 450 mg (n = 1) and 600 mg (n = 1).
“We consider the fact that anaphylaxis is much less frequent during maintenance significant,” Anagnostou said.
Most episodes involved urticaria, angioedema, erythema or other cutaneous symptoms (n = 11) and wheezing, coughing, dyspnea or other respiratory symptoms (n = 11).
Treatment included epinephrine (one dose, n = 9; two doses, n = 2), antihistamines (n = 9), albuterol (n = 6), oral steroids (n = 3) and overnight hospitalization (n = 1).
The researchers observed that peanut-specific IgE and Arah 2 were highly correlated (r = 0.91; P < .001).
Patients who experienced anaphylaxis showed significantly higher baseline levels of median peanut-specific IgE (100 kUA/L vs. 14.9 kUA/L; P = .001) and peanut Arah 2 (65.3 kUA/L vs. 13 kUA/L; P = .007), and they were also significantly older (11 years vs. 7 years; P = .001) compared with the nonanaphylaxis group.
Odds for anaphylaxis increased with each year increase in age after adjusting for peanut sIgE (OR = 1.54; 95% CI, 1.14-2.07) and for Arah 2 (OR = 1.45; 95% CI, 1.14-1.85).
Similarly, odds for anaphylaxis increased with each 1 kUA/L increase in Arah 2 (OR = 1.03; 95% CI, 1.01-1.05) and each 1 kUA/L increase in peanut sIgE (OR = 1.04; 95% CI, 1.01-1.08).
Anaphylaxis triggers included exercise (n = 3), viral illness (n = 2), doses taken on an empty stomach (n = 2), hot showers shortly after doses (n = 1) and accidental peanut exposure (n = 1), with no trigger identified for six episodes.
Considering the frequency of episodes and the triggers behind them, the researchers advised physicians to include information about avoidable triggers and epinephrine refresher training for caregivers and patients of appropriate age during patient education for peanut OIT.
“Doctors may share the information and data from studies like these to better inform their patients of long-term effects of food allergy therapies,” Anagnostou said.
Next, Anagnostou said that she and her team will evaluate therapy outcomes at 5, 10 and 15 years into long-term maintenance.
For more information:
Aikaterini (Katherine) Anagnostou, MD, MSc, PhD, FACAAI, can be reached at aikaterini.anagnostou@bcm.edu.
Perspective
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This letter to the editor reviews anaphylaxis episodes in a cohort of 75 children who completed real-world peanut OIT at a single academic center. This study addresses an important knowledge gap related to limited long-term and real-world data about children on OIT.
It is interesting — and misleading — that the authors chose to start the paper by saying that peanut OIT is a safe therapeutic option, but then go on to describe anaphylaxis in 17% of their cohort, which occurred during build-up and maintenance and with 40% of episodes with no identifiable trigger.
In addition, a systematic review and meta-analysis by Chu and colleagues in 2019 showed that available peanut OIT considerably increased allergic and anaphylactic reactions over avoidance or placebo.
This was a small study, but it is important to review any available data that can help us better understand potential factors, such as age and IgE, that may impact risk or success of treatment.
Overall, the results are similar to what has been found in other studies and what I have seen in clinical trials. Larger studies are needed to further investigate these findings, but this information can be used in shared decision-making with families prior to enrolling in real-world or clinical trial OIT.
As the authors discussed, it is key to educate participants and caregivers about potential triggers for anaphylaxis and to ensure that they are prepared on how to administer epinephrine. In addition, this study highlights the need for safer treatment approaches.
Reference:
Chu DK, et al. Lancet. 2019;doi:10.1016/S0140-6736(19)30420-9.
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