Reviews and feature article
Evaluating primary end points in peanut immunotherapy clinical trials

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Food immunotherapy has been the focus of several allergy research initiatives over the last decade. Although many questions remain unanswered, the evidence suggests that this treatment might be available in the near future outside clinical trials. Additionally, pharmaceutical companies, in light of promising early-stage results, have shown interest in developing commercially available products, thus increasing the likelihood that new immunotherapy treatments will be introduced, especially for peanut allergy. Given this optimistic scenario and given the prospect of rigorously developed products for peanut allergy treatment, each allergist will need to understand the specificities of these treatments and their expected efficacy and adverse event profiles. Thus it is imperative that allergists understand the differences in efficacy between the different management options, as well as how the end points are measured in the relevant literature. However, given the significant heterogeneity detected among food immunotherapy trials, this task might not be as straightforward as desired. This article aims to dissect how primary efficacy end points are defined and assessed to facilitate understanding of the design of these trials and the potential effect that this variation might have on the reported outcomes.

Section snippets

Methods

A systematic review of the literature was performed by using the same methodology as in the meta-analysis by Nurmatov and colleagues,24, 25 although in this case the search was limited to peanut-related key words. This strategy was complemented by a manual search of the relevant databases, and every study on peanut immunotherapy was considered, regardless of the route of administration (oral immunotherapy [OIT], epicutaneous immunotherapy, sublingual immunotherapy [SLIT], or subcutaneous

Definition of clinical efficacy

There are clear similarities between conventional (aeroallergen and Hymenoptera venom) AIT and food AIT, such as the use of a dose-escalation scheme and the immunomodulation driven by the treatment. Patient safety is the main objective in both cases and also a factor that limits a broader use of the treatment.49, 50 However, although there is a robust and well-developed consensus guiding population selection in aeroallergen AIT51 and the selection of validated clinical end points52 for clinical

Assessment of clinical efficacy

Once clinical efficacy has been defined, researchers must state how this variable will be measured. In some cases a treatment is considered efficacious if patients reach the MP,43, 48 but usually, an exit challenge is required. Despite DBPCFC being the gold standard in food allergy diagnosis,9 it is a cumbersome procedure. In some studies an open exit challenge has been used to evaluate patients' clinical reactivity, as well as treatment efficacy.33, 46, 47 Studies in which efficacy is measured

Discussion

This is a momentous period in the history of food AIT, despite several unanswered questions62 and an ongoing debate on whether this management approach is ready for routine clinical practice.63, 64, 65, 66, 67, 68, 69 The most recent EAACI guidelines marked a step toward widespread introduction of immunotherapy, signaling that it could soon be suitable for everyday care delivery1 in specialized centers. Now is the time to build up a solid evidence base, designing harmonized studies for the most

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  • Cited by (0)

    Disclosure of potential conflict of interest: P. Rodriguez del Rio received research funding from the Health Research Fund of Carlos III Health Institute, Foundation for Biomedical Research of the Niño Jesús University Children's Hospital, and Spanish Society of Allergology and Clinical Immunology Foundation and reports honoraria for consultancy and/or advisory board and/or lectures from ALK-Abelló, HAL-Allergy, FAES Pharma, LETI Pharma, Merck, Aimmune, Allergy Therapeutics, MEDA Pharma, and Novartis. C. Escudero received research funding from the Health Research Fund of Carlos III Health Institute, Foundation for Biomedical Research of the Niño Jesús University Children's Hospital, Spanish Society of Allergology and Clinical Immunology Foundation, and Aimmune Therapeutics; serves as a consultant for ALK-Abelló, Leti, and Novartis Pharma; and has received lecture fees from Spanish Society of Allergology and Clinical Immunology and Porto University. S. Sánchez-García received research funding from the Health Research Fund of Carlos III Health Institute, Foundation for Biomedical Research of the Niño Jesús University Children's Hospital, and Spanish Society of Allergology and Clinical Immunology Foundation; is a consultant for ALK-Abelló and Allergy Therapeutics; and receives lecture fees from Nutricia, Novartis, GlaxoSmithKline, Leti, and Allergy Therapeutics. M. D. Ibáñez receives research funding from the Health Research Fund of Carlos III Health Institute and Aimmune Therapeutics, serves as a consultant for Merck and Novartis, and has received lectures fees from the Spanish Society of Allergology and Clinical Immunology, Leti, Merck, FAES, and MSD. B. P. Vickery is a consultant to Aimmune Therapeutics, reports employment and stock options from Aimmune in the 12 months before publication, is a consultant to the Gerson Lehman Group, and is a member of the Outcomes Research Advisory Board at Food Allergy Research and Education.

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