Algorithms in allergen immunotherapy in allergic rhinoconjunctivitis
Authors: Oliver Pfaar, Elizabeth Angier, Antonella Muraro, Susanne Halken, Graham Roberts
Journal: Allergy (2020)

Allergic rhinoconjunctivitis (ARC) is one of the commonest chronic diseases worldwide with increasing prevalence.1 Allergen immunotherapy (AIT) has been thoroughly established as the only disease-modifying treatment option in patients with IgE-mediated allergic diseases such as AR with/without concomitant allergic asthma.2, 3 The European Academy of Allergy and Clinical Immunology (EAACI) has recently published multiple systematic reviews and meta-analyses on the clinical efficacy and tolerability of this treatment in several indications such as ARC,4 allergic asthma,5 and prevention6 as a basis for the recommendations in different clinical guidelines in the field following the AGREE-II approach.7 The EAACI guideline on AIT in ARC8 recommends both the subcutaneous (SCIT) and the sublingual (SLIT, liquids, or tablets) forms of AIT in general. It also highlights the need for a product-specific evaluation as the formal systematic reviews and meta-analyses in this indication revealed a high grade of heterogeneity. Besides giving evidence-based clinical recommendations, this guideline also aimed to provide guidance for daily clinical routine such as indications, contraindications, the pros and cons for both application routes of AIT, as well as the need for a thorough education of patients, and collaboration of prescribing physician and patients with shared decision-making throughout the course of treatment. In this article, the authors aimed to provide an algorithm which refers to the recommendations and guidance in the EAACI guideline.8 It can also be used by clinicians for decision-making and maintaining best practice of AIT in daily routine (Figure 1). AIT is indicated when (a) a patient suffers from moderate-to-severe allergic rhinoconjunctivitis following the "Allergy and its impact on Asthma" (ARIA) definitions,1 (b) allergic sensitization to the underlying, clinical relevant allergen(s) can be demonstrated by means of skin prick tests (SPT) or serum-specific IgE, (c) optimal pharmacotherapy is insufficient (and documented as such) or unacceptable due to side effects, and (d) avoidance measures are limited or not effective (and documented as such). If all these prerequisites are followed, before initiation of AIT absolute contraindications should be ruled out and relative contraindications should be decided on a case-to-case basis in line with recent EAACI Position Papers and guidelines.7, 9 In polyallergic patients, the most clinically relevant allergens should be identified by history, SPT, IgE, and allergen provocation testing if available. The one or two most clinically relevant allergens should be used for AIT. Simultaneously starting treatment with two (non-homologous) allergens is possible but should be decided on a case-to-case basis and should be reserved for clinics or practices who have a lot of experience with AIT. A product-specific evaluation of the single allergen extract focusing on documented efficacy and tolerability in the respective target population and indication is strictly recommended as a high grade of heterogeneity is demonstrated in systematic review and meta-analyses in this field.4-6 Patients should be thoroughly educated regarding the principles of the procedures of AIT in general including possible outcomes. They also need to appreciate and be able to commit to regular adherence, adequate reporting of possible adverse events, time for regular appointments, and consultation with prescribing physician as well as the duration of the whole treatment course. It is also essential that all healthcare professionals involved in this treatment are competent and regularly retrained in the recognition and management in case of adverse allergic reactions during AIT including anaphylaxis. The required emergency equipment should be regularly checked and available on site. Effectiveness and tolerability as well as adherence should be assessed on a regular basis. If efficacy is lacking after 1 year or in case of severe systematic reactions, based on a case-to-case decision, the course of AIT should probably be stopped. In line with the Summary of Product Characteristics of different allergen extracts, the whole treatment course of AIT (both SCIT and SLIT) is 3-5 years. On the basis of current EAACI guidelines,7, 8 clinical recommendations can be given for the route of administration (SCIT vs SLIT), different treatment-schedules, and formulations in both pollen-allergic (Figure 2) and mite-allergic patients (Figure 3) with ARC. Dr Pfaar reports grants and personal fees from ALK-Abelló, grants and personal fees from Allergopharma, grants and personal fees from Stallergenes Greer, grants and personal fees from HAL Allergy Holding BV/HAL Allergie GmbH, grants and personal fees from Bencard Allergie GmbH/Allergy Therapeutics, grants and personal fees from Lofarma, grants from Biomay, grants from Circassia, grants and personal fees from ASIT Biotech Tools SA, grants and personal fees from Laboratorios LETI/LETI Pharma, personal fees from MEDA Pharma/MYLAN, grants and personal fees from Anergis SA, personal fees from Mobile Chamber Experts (a GA2LEN Partner), personal fees from Indoor Biotechnologies, grants from GlaxoSmithKline, personal fees from Astellas Pharma Global, personal fees from EUFOREA, personal fees from ROXALL, personal fees from NOVARTIS, from SANOFI AVENTIS, outside the submitted work. Dr Angier has nothing to disclose. Dr Muraro has nothing to disclose. Dr Halken reports personal fees and nonfinancial support from ALK-Abelló, outside the submitted work. Dr Roberts has nothing to disclose.