Starting from its distant introduction as an empirical treatment of hay fever, allergen immunotherapy (AIT) has been developed to achieve recognition of scientific evidence of efficacy and safety [1]. The progress has mainly concerned the qualitative improvement of allergen extracts for AIT, which have recently obtained pharmaceutical quality recognition from regulatory agencies [2]. However, the efficacy of a product for AIT demonstrated in controlled trials may not be reproduced in current practice if the prescription is not targeted on the individual characteristics of the patient, thus influencing negative opinions on such treatment.
The concept of personalized medicine as a diagnostic and therapeutic approach tailored to the medical needs of each patient [3] is currently revolutionizing all fields of medicine and in particular allergology. New opportunities are arising: technological progress combined with current scientific advances suggest the possibility of developing new comprehensive approaches to better manage patient health and target therapies to achieve the best outcomes in the management of a patient’s allergy. Actually, AIT meets the three main needs for precision medicine, which are identification of molecular mechanism of disease, diagnostic tools for the molecular mechanism and treatment blocking the mechanism [4].
To cope with the multiplication of allergic conditions, which are increasingly complex and multifactorial, the shift towards this new medicine has become inevitable. Allergology is therefore at a major turning point in its history: AIT and recent medical innovations are paving the way for a realistic “tailor-made approach” to the treatment and care of patients with respiratory allergies.
Indeed, such issue faces many challenges related to the patient’s management. Today, the increase in respiratory allergy triggers, mainly related to air pollution and climate change is accompanied by an increase in the prevalence of asthma, rhinitis and rhino-conjunctivitis [5]. In addition, respiratory allergies are still poorly diagnosed and their symptoms insufficiently controlled, thus illustrating the current limitations of care pathways for the management of allergy. They therefore generate high, sometimes avoidable, costs for the healthcare system and their societal impact is even more significant as they impair patient quality of life and are associated with severe comorbidities.
These challenges act as key drivers of the shift towards the tailoring of medical treatments to the individual characteristics, needs and preferences of a patient during all stages of care, including prevention, diagnosis, treatment and follow-up. This personalized medicine model is based on four fundamental/rooted pillars: personalization, prediction, prevention and patient participation.
The evolutionary path of the AIT approach has historically started from a prescription based on the etiological factor related to the mechanisms of the disease, proceeding through a better knowledge of the endotype, what today is defined as precision medicine, to a personalized medicine. The concept of personalized medicine comes directly by the one of personalized medicine, but enriches it with careful analysis and observation of the peculiar features of the patient we are treating. Just AIT, because it adapts to the spectrum of specific IgE of each individual subject, changing the course and natural history of the disease, is a clear model of precision and personalized medicine [6].
The prescription of AIT must first be based on a personalized diagnosis of the clinical phenotype using, for example, biomarkers that can guide medical prognosis and the targeting of treatments.
Regarding the possible predictive biomarkers, several have been hypothesized and analysed, although there are no predictive ones. The EAACI Task Force "Biomarkers for monitoring the clinical efficacy of allergen Immunotherapy" has acted with the aim to analyse possible predictive biomarkers of efficacy, indicating as main markers the high levels of specific serum IgE and the symptoms in contact with the specific allergen. Furthermore, the ratio of specific IgE vs total IgE (sIgE/tIgE) was also evaluated, particularly in AIT household dust mite (HDM) or grass pollen, with controversial results, where some studies indicated the ratio as a possible response marker, and others failed to detect a real reliability. Several studies indicated a possible correlation between several subtypes of IgG (IgG1, sIgG4) and clinical outcomes, but another time without general consensus [7].
This first step must be based on a precise characterization of the sensitization profile using tools adapted to the patient profile ("classic" in-vivo IgE antibody tests and/or in-vitro molecular allergy tests). This diagnosis will then guide the definition of therapeutic objectives tailored to each patient. On the one hand, AIT can be used as an effective and personalized etiological treatment. Indeed, the healthcare professional will have numerous levers for adapting the treatment to the physio-pathological mechanisms involved (allergen composition, schedule and dosage of administration and efficacy measures, and definition of monitoring modalities). On the other hand, AIT is also prescribed to develop the patient's immunological memory so as to for example, prevent the onset of asthma, new sensitizations and reduce asthma medication intake. Importantly, patient empowerment during all stages of care, through the definition of personalized treatment plans and shared medical decision-making, is necessary to fully involve individuals with respiratory allergies in decisions about their care. As already said before AIT is a paradigmatic therapeutic approach to precision and personalized medicine, and in this field molecular diagnostics can provide important information about the patient and his therapy. For several years now, not only has the use of molecular diagnostics been advocated, but protocols have also been created that indicate how to use this method in order to identify the best approach of AIT. It has been observed that, after reanalysing patients with molecular diagnostics, the choice of AIT previously prescribed could be reviewed in almost half of the patients. For these reasons, to make the therapy with AIT more and more effective, the molecular diagnosis, for the patients to be treated, must be encouraged [8].
Finally, driven by the challenges mentioned above and nourished and disseminated by this first model of personalized medicine, future developments in allergology will favour the growth and deployment of a new model of "customized" medicine. The integration of large amounts of omics datasets, the discovery of new biomarkers of endotypes, treatment responses and monitoring, and the development of targeted biological therapies will make it possible to stop the initiation or halt the progression of the allergic march, to reduce the burden of disease and to increase patient satisfaction.
