AIT (allergen immunotherapy): a model for the “precision medicine”
© Passalacqua and Canonica. 2015
Received: 25 June 2015
Accepted: 6 August 2015
Published: 8 October 2015
The interpretation of medical approaches, especially therapy, evolved rapidly in the last century. Starting from the simple description of symptoms, we moved to the pathophysiological descriptions, to the evidence-based medicine, until the so-called “precision medicine”. This latter can be defined as a structural model aimed at customizing healthcare, with medical decisions/products tailored on an individual patient at a highly detailed level. In this sense, allergen immunotherapy represents an optimal model of “precision medicine”, since we know and describe symptoms, function, aetiological agents at molecular level, and we have the possibility to intervene on the natural history of the disease. If considered under the point of view of pharmaco-economy, that is prescribing the optimal treatment to the right patient, allergen immunotherapy represents an almost-ideal model of precision medicine.
The medical science slowly evolved, along centuries, from the Hippocratic “humours”  to a more pathophysiology-oriented interpretation of clinical phenomena [2–4], until the current “omic” sciences. Thus, it seems that a more and more potent magnifying lens has become available to study and understand diseases. In addition, it is clear that the clinical science, the mechanistic knowledge and the translational applications are becoming more and more strictly interconnected.
The “blockbuster approach” (i.e. one size fits all) cannot be currently used with many of the very expensive treatments available, where the best cost/effective treatment should be provided. This also implies a greater professional and responsible involvement of specialists in properly selecting patients. The “precision medicine” can be defined as a structural model aimed at customizing healthcare at best, with medical decisions, practices, and/or products tailored on an individual patient. The term of “personalized medicine” is also used interchangeably.
to improve the clinical outcomes and their predictability;
to reduce the side effects caused by a possibly inappropriate treatment;
to increase the quality of life;
to encourage patients’ compliance due to a perceived clinical improvement;
to optimise the use of healthcare resources.
Personalized medicine is still a critical aspect in the most complex, prevalent and expensive chronic diseases, such as COPD  or asthma in general , where a targeted approach would heavily affect the management.
Allergen immunotherapy (AIT)
Allergen immunotherapy remains one of the best candidates to a personalized-medicine approach since we currently know: (a) the main immunological and molecular events underlying the allergic symptoms ; (b) which are the more specific and sensitive standard diagnostic tests to identify the IgE-mediated reactions; (c) the relevant molecules involved in allergic reactions [17, 18]; (d) purified and standardized documented products for effective and safe AIT.
Allergen immunotherapy has a unique immunological rationale, tailored to the specific IgE spectrum of each individual. In addition, AIT can modify the immune response against the allergen for which the treatment is designed, thus allowing to modify the natural history of the disease itself , and this is a unique feature in treating allergies. In addition, the AIT long term effect remains a unique feature of great impact in the pharmaco-economic evaluation, since no other allergy treatment has this specific characteristic .
Nonetheless, we still need biomarkers which could be predictive of the expected efficacy and, consequently, the identification of the eligible patients, with a direct economic implication. We, would highlight other critical issues for a correct and effective AIT. Certainly we would need a more spread knowledge on molecular allergy, to be ourselves more adherent to the definition of personalized medicine. Moreover, a clear characterization and definition of commercial products for vaccination is also urgently needed. A precision medicine requires precision approaches, whereas nowadays, for many commercial products the characterization remains poor, and in some cases an experimental proof of efficacy is lacking . This is the reason why, regulatory authorities are strenuously trying to provide clear rules for the marketing, and for AIT products commercial authorizations [25, 26].
According to the current knowledge of mechanistic aspects, to the detailed identification of aetiological agents, and the not negligible longstanding experience, AIT, in the context of the other available therapies for respiratory allergy, is the most “personalized” treatment  (Fig. 2). Possibly, in the past, the concept of AIT as Precision Treatment was not properly considered or emphasized, but AIT was and still is upfront in this context. We are aware that more precise information and markers will be provided by systems medicine  and networks projects [29, 30]: these will further improve AIT indication, patient selection for clinical trials, prescription and, consequently, effectiveness and cost/effectiveness.
GP and GWC have equally contributed in the conception and drafting of the article. Both authors read and approved the final manuscript.
None to disclose.
Compliance with ethical guidelines
Competing interest The authors declare that they have no competing interests.
Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. 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.
- Corpus Hyppocraticum (1839) Émile Littré: Oeuvres Completes (Traduction Nouvelle, avec le texte grec en regard), vol I. J.-B. Baillière, ParisGoogle Scholar
- Harvey W (1628) Exercitatio Anatomica de Motu Cordis et Sanguinis in animalibus. Sp Coll Hunterian Y.7.13, FrankfurtGoogle Scholar
- Virchow RK (1858) Die Cellularpathologie in ihrer Begründung auf physiologische und pathologische Gewebenlehre, BerlinGoogle Scholar
- Lister J (1967) Antiseptic principle in the practice of surgery. Br Med J 2(5543):9–12View ArticlePubMedPubMed CentralGoogle Scholar
- Brasier AR (2013) Identification of innate immune response endotypes in asthma: implications for personalized medicine. Curr Allergy Asthma Rep 13:462–468View ArticlePubMedPubMed CentralGoogle Scholar
- Agache IO (2013) From phenotypes to endotypes to asthma treatment. Curr Opin Allergy Clin Immunol 13:249–256PubMedGoogle Scholar
- Bieber T (2013) Stratified medicine. Future Medicine Ltd. ISBN: 978-1-78084-318-6Google Scholar
- Braido F, Holgate S, Canonica GW (2012) From “Blockbusters” to “biosimilars”: an opportunity for patients, medical specialists and health care providers. Pulm Pharmacol Ther 25:483View ArticlePubMedGoogle Scholar
- Fuchs VR (2013) The gross domestic product and health care spending. N Engl J Med 369(2):107–109View ArticlePubMedGoogle Scholar
- Hamburg MA, Collins FS (2010) The path to personalized medicine. N Engl J Med 363:301–304View ArticlePubMedGoogle Scholar
- Rowe SM, Heltshe SL, Gonska T, Donaldson SH, Borowitz D, Gelfond D et al (2014) Clinical mechanism of the cystic fibrosis transmembrane conductance regulator potentiator ivacaftor in G551D-mediated cystic fibrosis. Am J Respir Crit Care Med 190:175–184View ArticlePubMedPubMed CentralGoogle Scholar
- Katz LE, Gleich GJ, Hartley BF, Yancey SW, Ortega HG (2014) Blood eosinophil count is a useful biomarker to identify patients with severe eosinophilic asthma. Ann Am Thorac Soc 11(4):531–536View ArticlePubMedGoogle Scholar
- Liu Y, Zhang S, Li DW, Jiang SJ (2013) Efficacy of anti-interleukin-5 therapy with mepolizumab in patients with asthma: a meta-analysis of randomized placebo-controlled trials. PLoS One 8(3):e59872. doi:10.1371/journal.pone.0059872 (Epub 2013 Mar 27) View ArticlePubMedPubMed CentralGoogle Scholar
- Agusti A (2014) The path to personalised medicine in COPD. Thorax 69:857–864View ArticlePubMedGoogle Scholar
- Fajt ML, Wenzel SE (2015) Asthma phenotypes and the use of biologic medications in asthma and allergic disease: the next steps toward personalized care. J Allergy Clin Immunol 135:299–310View ArticlePubMedGoogle Scholar
- Akdis CA, Akdis M (2015) Mechanisms of allergen-specific immunotherapy and immune tolerance to allergens. World Allergy Organ J 8(1):17View ArticlePubMedPubMed CentralGoogle Scholar
- Canonica GW, Ansotegui IJ, Pawankar R, Schmid-Grendelmeier P, van Hage M, Baena-Cagnani CE et al (2013) A WAO-ARIA-GA2LEN consensus document on molecular-based allergy diagnostics. World Allergy Organ J. 6(1):17. doi:10.1186/1939-4551-6-17 View ArticlePubMedPubMed CentralGoogle Scholar
- Sastre J (2013) Molecular diagnosis and immunotherapy. Curr Opin Allergy Clin Immunol 13:646–650View ArticlePubMedGoogle Scholar
- Burks AW, Calderon MA, Casale T, Cox L, Demoly P, Jutel M et al (2013) Update on allergy immunotherapy: American Academy of Allergy, Asthma & Immunology/European Academy of Allergy and Clinical Immunology/PRACTALL consensus report. J Allergy Clin Immunol. 131(5):1288–1296View ArticlePubMedGoogle Scholar
- Canonica GW, Cox L, Pawankar R, Baena-Cagnani CE, Blaiss M, Bonini S et al (2014) Sublingual immunotherapy: World Allergy Organization position paper 2013 update. World Allergy Organ J 7(1):6View ArticlePubMedPubMed CentralGoogle Scholar
- Passalacqua G, Canonica GW (2015) Allergen immunotherapy: focus on tablets. Ann Allergy Asthma Immunol 115:4–9View ArticlePubMedGoogle Scholar
- Passalacqua G (2011) Specific immunotherapy: beyond the clinical scores. Ann Allergy Asthma Immunol 107:401–406View ArticlePubMedGoogle Scholar
- Hankin CS, Cox L (2014) Allergy immunotherapy: what is the evidence for cost saving? Curr Opin Allergy Clin Immunol 14:363–370View ArticlePubMedGoogle Scholar
- Jutel M, Agache I, Bonini S, Burks AW, Calderon M, Canonica W et al (2015) International consensus on allergy immunotherapy. J Allergy Clin Immunol. doi:10.1016/j.jaci.2015.04.047
- Kaul S, May SL, Vieths S (2011) Regulatory environment for allergen-specific immunotherapy. Allergy 66:753–764View ArticlePubMedGoogle Scholar
- Bonini S (2012) Regulatory aspects of allergen-specific immunotherapy: Europe sets the scene for a global approach. World Allergy Organ J 5:120–123View ArticlePubMedPubMed CentralGoogle Scholar
- Jameson JL, Longo LS (2015) Precision medicine: personalized, problematic and promising. N Eng J Med 372:2229–2234View ArticleGoogle Scholar
- Gustafsson M, Colm EN, Zhang H, Barabási AL, Baranzini S, Brunak S et al (2014) Modules, networks and systems medicine for understanding disease and aiding diagnosis. Genome Med 6:82View ArticlePubMedPubMed CentralGoogle Scholar
- Bousquet J, Anto JM, Sterk PJ, Adcock IM, Chung KF, Roca J et al (2011) Systems medicine and integrated care to combat chronic noncommunicable diseases. Genome Med 3(7):43View ArticlePubMedPubMed CentralGoogle Scholar
- Bousquet J, Addis A, Adcock I, Agache I, Agusti A, Alonso A et al (2014) Integrated care pathways for airway diseases (AIRWAYS-ICPs). Eur Respir J 44:304–323View ArticlePubMedGoogle Scholar