Volume 124, Issue 6 , Pages 1351-1352, December 2009
Adverse reactions during peanut oral immunotherapy home dosing
Article Outline
To the Editor:
Oral immunotherapy (OIT) is increasingly being investigated as a potential treatment for peanut and other food allergies, with a recent study demonstrating evidence of clinical desensitization and immunologic changes suggesting the development of long-term tolerance.1 Unlike traditional subcutaneous immunotherapy for inhalant allergens, peanut OIT is administered daily, with the vast majority of doses given at home. In our peanut OIT protocols, subjects are seen in the research unit for observed dose escalations every 2 weeks, and subsequent doses are given at home. In the open-label study of peanut OIT, home doses were generally well tolerated.2 The incidence of allergic reactions with any home dose was 3.5%, with mild upper respiratory and skin symptoms being the most common complaints.
Despite the infrequent incidence of symptoms with peanut OIT home dosing, certain patterns of reactions have surfaced during this phase. Characterizing these reactions and identifying potential triggers or factors that predispose to reactions might improve the safety of home dosing. Reactions occurring during investigational OIT or any immunotherapy protocol are challenging to study prospectively because of ongoing modifications in the protocol and recommendations that are instituted to prevent further reactions. In subcutaneous aeroallergen immunotherapy, asthma has been identified as a risk factor for systemic reactions, prompting recommendations to evaluate respiratory symptoms and consider objective measures of airway function during administration.3 Researchers studying milk and egg OIT noted certain “augmentation factors” that decrease threshold doses (namely infection, exercise, pollen allergy, and irregular intake),4 and identifying these factors and reducing the immunotherapy dose prevented further allergic reactions.
We have noted 5 patterns associated with a propensity for reactions to a previously tolerated dose of peanut OIT, including several not previously described. It is interesting that these factors would provoke symptoms after a given OIT dose when, in many of the examples noted, the dose had been tolerated for weeks to months without symptoms. Table I lists selected examples illustrating the observed patterns: (1) concurrent illness, (2) suboptimally controlled asthma, (3) timing of dose administration after food ingestion, (4) physical exertion after dosing, and (5) dosing during menses. Addressing these factors (Table II) has improved the safety profile of our peanut OIT protocol. Although some of our recommendations mirror those instituted in subcutaneous immunotherapy protocols, most are unique to OIT administration. We expand on reports from other research centers,4, 5 which have described triggers such as infection, exercise, pollen allergy, and irregular intake, and this is the first report involving protocols for peanut allergy.
Table I. Examples of reactions during peanut OIT home dosing
| Subject no. | Age at reaction (mo) | Pattern | Reaction | Dose (mg) | Length of time on OIT (mo) | Length of time on dose | Baseline IgE level (kU/L) | IgE level at time of reaction (kU/L) | Treatment | Recommendations to this subject |
|---|---|---|---|---|---|---|---|---|---|---|
| 1 | 70 | Fever | AE, LR | 300 | 12 | 5 mo | 23.6 | 13.9 | H1, E, A | Hold dose if ill |
| 2 | 131 | Fever | AE, U, LR | 1200 | 19 | 3 mo | >100 | 136.5 | H1, E, CS, A | Hold dose if ill |
| 3 | 38 | Asthma | LR | 300 | 10 | 4 mo | 22.7 | 9.3 | H1, A | Start inhaled CS |
| 4 | 83 | Empty stomach | U, LR, G | 1800 | 27 | 7 mo | >100 | 115 | H1, A | Take all doses with meal |
| 5 | 102 | Exertion | LR | 2400 | 49 | 2 mo | 58.3 | 4.7 | H1, A | Avoid exercise for 2 h after dose |
| 6 | 99 | Exertion | U, LR | 3000 | 47 | 2 d | 73.1 | 7.3 | H1, CS | Avoid exercise for 2 h after dose; decrease dose to 2400 mg |
| 7 | 145 | Menses and exertion | AE,U, UR, LR, G | 4000 | 20 | 9 mo | 85.1 | 59.5 | H1, E, CS | Discontinued participation in study after second occurrence |
Table II. Recommendations for future oral immunotherapy investigations
| Hold daily dose if febrile or ill with symptoms of viral illness (eg, upper respiratory tract infection, gastroenteritis). |
 Resume dosing at home if <3 missed daily doses. |
| Return to research unit for observed dose if 3-5 missed daily doses. |
| Consider repeat desensitization or significant dose reduction if >5 missed daily doses. |
| Closely monitor lower and upper respiratory symptoms. |
| Initiate asthma controller medication if needed. |
| Perform peak flow and spirometric monitoring. |
| Ensure optimal control of allergic rhinitis. |
| Take daily OIT dose with meal or snack |
| In subjects with exercise-induced symptoms, limit exertion for 2 hours after dosing. |
| Closely monitor during menstrual cycle, especially when coupled with infection or exercise. |
We have observed that dosing during febrile illnesses has been associated with systemic reactions to previously tolerated peanut OIT doses. We recommend withholding OIT during acute illnesses and advise subjects to resume dosing at home if fewer than 3 doses are missed. If 3 to 5 doses are missed, subjects return to the research unit for observed dosing. Those who miss more than 5 days of dosing might require significant dose reduction or repeat desensitization.
In our open-label study2 asthma was associated with a higher rate of chest symptoms during OIT. Of the subjects reporting chest symptoms during home dosing, 82% had coexisting asthma. Several subjects receiving peanut OIT noted cough and wheezing after doses. Some also had chronic cough or exercise-induced respiratory symptoms. Although we did not observe changes in pulmonary function in these subjects, their symptoms improved with the initiation of asthma controller medications (Table I), highlighting the importance of diagnosing and treating comorbid atopic conditions. Regular peak flow measurements and pulmonary function testing have been implemented to optimize asthma control.
It has not been uncommon for a subject taking a daily OIT dose without eating a meal or snack in the 2 hours before dosing to have symptoms with a dose that had been previously tolerated; taking the same dose with a substantial meal or snack the next day and thereafter prevents further reactions. Additionally, several subjects have experienced allergic symptoms with exercise after OIT dosing, and we advise these subjects to avoid exertion for 2 hours after dosing. Finally, 1 subject had several systemic reactions when menses was coupled with exercise despite no symptoms with daily dosing in the interval between episodes and was eventually withdrawn from the study. She was not taking other medications (eg, nonsteroidal anti-inflammatory drugs). Of note, she did not have systemic reactions each time she exercised during menses. At this time, the role of menses is unclear, and further study is needed.
In the studies to date, peanut and food OIT have a good safety profile, and home dosing is infrequently associated with adverse reactions.2, 6 However, allergic symptoms should be expected, and subjects and their families should be counseled about circumstances associated with an increased possibility of reacting to previously tolerated OIT doses. As OIT for food allergy becomes increasingly studied in research settings, implementing these recommendations and modifications can improve the safety of these experimental protocols.
References
- Clinical efficacy and immune regulation with peanut oral immunotherapy. J Allergy Clin Immunol. 2009;124:292–300e1-97
- Safety of a peanut oral immunotherapy protocol in children with peanut allergy. J Allergy Clin Immunol. 2009;124:286–291e1-6
- . Allergen immunotherapy: a practice parameter second update. J Allergy Clin Immunol. 2007;120(suppl):S25–S85
- . Specific oral tolerance induction in food allergy in children: efficacy and clinical patterns of reaction. Allergy. 2007;62:1261–1269
- . A protocol for oral desensitization in children with IgE-mediated cow's milk allergy. Allergy. 2004;59:980–987
- A randomized, double-blind, placebo-controlled study of milk oral immunotherapy for cow's milk allergy. J Allergy Clin Immunol. 2008;122:1154–1160
Disclosure of potential conflict of interest: P. Varshney received the National Institutes of Health T32 Training Grant. B. P. Vickery has received research support from the Thrasher Research Foundation. J. A. Bird has received research support from the Food Allergy Initiative. A. M. Scurlock has received research support from the National Institutes of Health. T. T. Perry has received research support from the National Institutes of Health and the Robert Wood Johnson Foundation. S. M. Jones is a consultant for and board member of the Food Allergy & Anaphylaxis Network and has received research support from the National Institutes of Health and DYAX Corporation. A. W. Burks is a Consultant for ActoGeniX NV, Intelliject, McNeil Nutritionals, and Novartis; is a minority stockholder of Allertein and MastCell, Inc; is on the Advisory Board for Dannon Co. Probiotics; is on the Expert Panel for Nutricia; has received research support from the National Institutes of Health, the Food Allergy & Anaphylaxis Network, and the Wallace Research Foundation; has served as an expert witness on the topic of food allergies; is on the Medical Board of Directors for the Food Allergy & Anaphylaxis Network and the Dermatological Allergy Committee for the American College of Allergy, Asthma & Immunology; is a member for the National Institutes of Health Hypersensitivity, Autoimmune and Immune-mediated Disease Study Section; and is on the Journal of Allergy and Clinical Immunology reviewer board. The rest of the authors have declared they have no conflict of interest.
PII: S0091-6749(09)01461-4
doi:10.1016/j.jaci.2009.09.042
© 2009 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
Volume 124, Issue 6 , Pages 1351-1352, December 2009
