Oral immunotherapy and anti-IgE antibody treatment for food allergy

Umetsu et al. World Allergy Organization Journal (2015) 8:20 DOI 10.1186/s40413-015-0070-3 journal REVIEW Open Access Oral immunotherapy and anti-IgE antibody treatment for food allergy Dale T. Umetsu1*, Rima Rachid2 and Lynda C. Schneider2 Abstract Food allergy is a major public health problem affecting nearly 10 % of children in most industrialized countries. Unfortunately, there are no effective therapies for food allergy, relegating patients to simply avoid the offending foods and treat reactions that occur on accidental exposure. Recently however, studies suggest that food immunotherapy may provide a promising new approach to food allergy, particularly using the oral form of immunotherapy (OIT). Enthusiasm for this approach though must be tempered because of the significant allergic reactions that often occur with OIT that tends to limit its use to patients with less severe disease. On the other hand, recent studies suggest that concomitant treatment of patients with omalizumab (anti-IgE monoclonal antibody) during the updosing phase of OIT may greatly reduce the allergic reactions associated with OIT, even in high-risk patients. This combined method may provide a novel approach to successfully and rapidly treat a large fraction of patients with high-risk food allergy. Keywords: Food allergy, Peanut, Oral immunotherapy, Desensitization, Milk Introduction Food allergy is a serious public health problem that affects 4-8 % of children in the US [1, 2]. In Australia, the prevalence of peanut allergy alone is 3 % in young children [3]; in the UK it is 2 % of 8-year-old children. In the US, 5 % of adults are estimated to have food allergy; 1.8 % have peanut allergy. Moreover, the prevalence of food allergy appears to have doubled or even quadrupled over the past 15 years in the US, UK and China [4, 5]. Globally, the number of patients with food allergy is estimated to be around 220-250 million [6]. In this review we will focus on IgE-mediated food allergy; non-IgE mediated reactions, such as celiac disease, eosinophilic esophagitis, lactose intolerance or food poisoning, will not be discussed. In IgE-mediated food allergy, reactions begin when allergen binds to IgE bound to the surface of mast cells or basophils through high-affinity IgE receptors (FcεR1), triggering the rapid release of mediators, generally within minutes, including histamine and leukotrienes that cause the symptoms of allergy. Unfortunately for patients with food allergy, there are no FDA or EMA approved therapies for food allergy, and the standard of care is allergen avoidance and prompt * Correspondence: 1 Genetech, One DNA Way, MS 453b, South San Francisco, California 94080, USA Full list of author information is available at the end of the article treatment of allergic reactions when they develop after accidental ingestion. However, even when attempting strict avoidance, each patient on average develops a significant allergic reaction every 1-4 years, due to the fact that the major food allergens are often hidden in prepared foods, or may be present due to cross contamination. As a result, food allergy is currently the most common cause of anaphylaxis seen in emergency rooms across the US, with peanut allergy accounting for 50-60 % of fatal episodes of anaphylaxis [7]. Furthermore, food allergy can be very stressful and debilitating for patients and families, because allergic reactions, including anaphylaxis, occur unpredictably. Maladaptive behaviors and anxiety develop, reducing quality of life (QoL) in food allergic children to a greater degree than in children with rheumatologic disease or in children with insulin-dependent diabetes [8, 9]. Therefore, food allergy represents an important and urgent unmet medical need. Novel approaches to the treatment of food allergy To address this need, food immunotherapy has been investigated as a treatment and potentially disease modifying approach. Immunotherapy has been performed subcutaneously, sublingually, transdermally and orally [10]. However, the subcutaneous approach was abandoned many years ago due to safety concerns [11]; the sublingual and © 2015 Umetsu et al.; licensee BioMed Central. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Umetsu et al. World Allergy Organization Journal (2015) 8:20 transdermal approaches have both been shown to be safe, but efficacy is limited by a restricted dose capacity, i.e., the amount that can be absorbed through the skin or under the tongue [12]. Oral immunotherapy (OIT) is more effective than the other routes, in part because much larger doses can be administered, but safety has been a major limitation [13]. OIT is performed by administration initially of low oral doses, after which the dose is increased as tolerated. Using this method, OIT has been successful in desensitizing many patients to different foods including egg, milk, peanut and tree nut [10, 14, 15]. The goal of therapy in most cases is to reduce or eliminate the severity of reactions following accidental ingestion, which means tolerating relatively low oral maintenance doses; but occasionally, the goal of OIT has been to tolerate much greater maintenance (dietary) doses of the food. However, there is no consensus regarding the best specific protocol in terms of dosing schedule and timing of the doses, and currently OIT is still considered experimental, due to significant concerns regarding safety and long-term consequences, as discussed below. Although OIT can be effective in increasing the amount of food that can be tolerated by a food allergic individual, allergic reactions, including anaphylaxis, are frequently observed during the desensitization protocol. For example, >90 % of patients undergoing oral milk OIT develop reactions, and 10-20 % of patients require epinephrine at some point during the desensitization process [16]. A recent meta-analysis of OIT studies suggested that the frequent serious adverse reactions might outweigh the benefits of OIT [17, 18]. Moreover, due to frequent allergic reactions that prevent dose increases, OIT generally takes a median time of 20-60 weeks to reach maintenance doses, and the highest oral dose achieved is often below the target maintenance dose. Importantly, as many as 10-30 % of food allergic patients are refractory to desensitization, particularly in patients with higher initial food-specific IgE levels [19–23]. Given these safety issues, OIT is currently performed primarily in academic centers, and most experts strongly believe that it should NOT be recommended for use in the commun (...truncated)