Epicutaneous allergen administration: A novel approach for allergen-specific immunotherapy?

Abstract

tiontoitsprovenclinicalefficacy,itcanalterthenaturalhistoryof allergicdiseaseandproducesustainedclinicalremissionafterdiscontinuation. Challenges to specific allergen immunotherapy includetheneedforeffectiveandconvenientmethodsofdelivery; in this issue, Senti et al 6 describe the epicutaneous administration of specific allergen immunotherapy, testing grass pollen allergens in patients with seasonal rhinitis. Many novel approaches to allergen immunotherapy have been developed to increase the safety and efficacy of allergenic vaccines.Newallergenadjuvantshavebeenstudied,andmodified allergens have been introduced into clinical practice (eg, allergoids,depigmentedallergenextracts peptidesor smallamino acid sequences, recombinant allergens, hypoallergenic vaccines with modified IgE binding sites, or allergen‐CpG fusion molecules). 3 Although specific immunotherapy has proven to be beneficial in multiple studies, only a small percentage of patients with allergy agree to receive this treatment in clinical practice: it has been estimated that only 5% of patients in the United States with allergic rhinitis, asthma, or both (about 2.5 million) are given specific allergen immunotherapy. Inconvenience (ie, time-consuming procedures and the requirement for injections—the most common route of delivery) has been described as one of the primary reasons for discontinuation of specific allergen immunotherapy and is likely to be a major reason that patients do not even begin therapy. 4 Whereas subcutaneous specific allergen immunotherapy is effective and subcutaneous injection is the most common method of administration, noninvasive routes (eg, oral, intranasal) have been studied. Sublingual administration is an effective alternative to regular and subcutaneous injections. Although this method of delivery appears to be safe (not associated with life-threatening systemic reactions), local symptoms including angioedema in the mouth have been reported. 2 Moreover, sublingual immunotherapy is expensive, requiring the daily intake of large amounts of allergens. Furthermore, sublingual immunotherapy might be less effective than subcutaneous immunotherapy and might administer fewer antigens at a time. Therefore, alternative routes for delivery of allergen-specific immunotherapy are needed. The clinical efficacy of epicutaneous allergen administration was reported more than 50 years ago, when a French allergy specialist performed allergen-specific immunotherapy using needle scarification of the volar forearm and described improved or complete relieffromhayfever(foraslongas3weeks)inmostofthetreated patients. 5 Senti et al 6 report the results from a phase I/II study to evaluate the safety and efficacy of epicutaneous administration of specific allergen immunotherapy by using grass pollen allergens in patients with seasonal rhinitis. The authors applied pouches filled withpetroleumjellythatcontainedPhleumpratenseextracttothe patients’ upper arm for 48 hours, once weekly for 12 weeks, after tape-stripping of the skin. They report that, during the pollen season,patientsgivenepicutaneousadministrationofgrasspollen allergens had significantly reduced symptoms compared with patients given placebo. These findings are novel and interesting. However, the effects were not very strong: when they performed nasal provocation tests, Senti et al 6 did not observe a significant difference between patients given placebo and those givenverum, although therewas a trend toward attenuation of allergic responses in the verum arm of the study. Moreover, the use of rescue medication was not reduced in the group given grass pollen allergens. The study has some limitations, which are discussed by the authors in detail. 6