Speaker- Montserrat Gernandez-Rivas
The landscape of food oral immunotherapy (OIT) has witnessed a paradigm shift, supported by systematic reviews and meta-analyses demonstrating its efficacy in inducing desensitization while acknowledging the associated risks of systemic reactions and anaphylaxis. The 2018 EAACI guidelines for IgE-mediated food allergy first recommended OIT, particularly for persistent milk, egg, or peanut allergies in children, culminating in the FDA and EMA approval of Palforzia for peanut OIT in 2020. However, adverse event indications emerged during the buildup and maintenance phases, as evidenced by a 2017 study. Variations in OIT practices across Europe were revealed in the FIND study (2018-2019) involving 25,000 patients, with clinicians boasting seven to nine years of experience. Notably, 70% of patients received treatment without formal consent, underscoring significant variability in patient management. Despite guidelines, approximately 50% of patients received OIT regardless of contraindications, such as severe asthma or recent anaphylaxis, reflecting expert-based rather than evidence-based decisions. Heterogeneity was also observed in protocol characteristics, highlighting the need for standardized approaches in OIT implementation.
A systematic review from June 2015 to March 2020 analyzed 22 studies on milk, 23 on peanut oil, and 25 on other allergens, focusing on outcomes like desensitization, sustained unresponsiveness, quality of life (QoL), reaction severity at oral food challenges (OFC), and regular consumption of the culprit food. Desensitization was the most common outcome, but its definitions varied widely, including maintenance dose tolerance, threshold increase, or a specific target dose. Sustained unresponsiveness should have been more frequently investigated. QoL was rarely assessed, especially for milk and egg, but more often in peanut trials, largely due to pharmaceutical sponsorship. The review highlighted the variability in defining and achieving outcomes, emphasizing the need for standardized criteria and consistent methodologies, as outlined in the 2012 Practal Consensus for oral food challenges. The systematic review up to 2022 evaluated how practical guidelines were implemented in oral food challenge studies. It found that peanut studies adhered more closely to guidelines, whereas adherence was below 60% for milk and egg studies. Practical dosage protocols were rarely used, with stopping criteria applied in only 40% of peanut trials and never in milk and egg trials. Furthermore, the way reactivity was reported varied significantly. For instance, a patient reacting at 300 mg protein might have their reactive dose reported as a single or cumulative dose, leading to values like 300 mg or 444 mg, respectively. Some trials reported the highest tolerated dose instead, such as 100 mg, with a cumulative tolerated dose of 144 mg. This inconsistency in reporting creates confusion and complicates data interpretation. Thus, there is a clear need for harmonization and standardization of protocols, as highlighted by the reviewed studies.
The COMFA study, published last year by the CONFA Consortium, began with a literature review identifying 39 individual outcomes, from which 13 were selected for inclusion in a Delphi survey. The first round of Delphi involved 778 participants, but none of the outcomes achieved consensus, leading to additional outcomes being considered based on free text comments. In the second round, with 442 participants, 14 outcomes were evaluated, but again, no consensus was reached, with 13 outcomes achieving only 50-80% agreement. Finally, consensus was achieved for two core outcomes: allergic symptoms elicited by food exposure and quality of life. The participants in the Delphi rounds included researchers in food allergy, healthcare professionals, adult patients, and parents or caregivers of children with food allergies. Healthcare professionals and researchers unanimously agreed on including allergic symptoms as a core outcome, though there was variability among patients. The study concluded that quality of life and allergic symptoms should be included in all trials as core outcomes. At the same time, desensitization and sustained responsiveness, although not achieving consensus, should be considered in most trials due to their critical importance to some stakeholders. Other outcomes are recommended for specific trials based on stakeholder relevance.
The PPOINT study, published in the Journal of Biology, involved a panel of 36 highly experienced experts in oral immunotherapy (OIT) from various regions, including North America and Europe. These experts collaborated to standardize and harmonize patient preparation for OIT through a Delphi consensus exercise. They identified key themes, such as general considerations for counselling patients about OIT, factors to address during OIT, indications and contraindications for starting OIT, potential benefits and risks, risk mitigation strategies, and criteria for discontinuing OIT. From the 219 statements generated, consensus was reached on 189 statements, further refined into nine themes for inclusion in a consent form. These themes covered benefits, risks, outcomes, alternatives, and long-term management. Additionally, the experts developed a flow diagram to guide the initial evaluation and selection of potential OIT candidates, emphasizing careful patient assessment and informed consent tailored to individual patient needs and circumstances.
In another recent study, researchers introduced the OIT Control app, developed by the University of Navarra in Spain, to monitor immunotherapy remotely when patients administer doses at home. This app allows medical staff to record doses and reactions in real time, providing valuable data for caregivers and patients. By leveraging technology, the OIT Control app offers a convenient and efficient method for tracking OIT progress and managing treatment outside the hospital setting. The OIT Control app, developed by the University of Navarra in Spain, offers a comprehensive solution for monitoring oral immunotherapy remotely, enabling patients to manage their doses and reactions at home. The app provides instructions for dose administration and guidance on managing reactions and facilitates communication between patients, caregivers, and medical staff. In a clinical trial comparing the app with traditional paper diaries, the OIT Control group reported more reactions but demonstrated better treatment compliance. Notably, patients using the app were more likely to make appropriate adjustments in response to moderate adverse reactions, enhancing safety and patient satisfaction. These findings underscore the potential of technology-driven solutions to improve the management and protection of OIT, highlighting the importance of standardization and ongoing efforts to optimize clinical care in food allergy management.
European Academy of Allergy and Clinical Immunology (EAACI), 2024 31stMay-3rd June, Valencia.
