ARIA‐EAACI care pathways for allergen immunotherapy in respiratory allergy

Jean Bousquet | Oliver Pfaar | Ioana Agache | Anna Bedbrook | Cezmi A Akdis | G. Walter Canonica | Tomas Chivato | Mona Al‐Ahmad | Amir H Abdul Latiff | Ignacio J Ansotegui | Claus Bachert | Abdullah Baharuddin | Karl‐Christian Bergmann | Carsten Bindslev‐Jensen | Leif Bjermer | Matteo Bonini | Sinthia Bosnic‐Anticevich | Isabelle Bosse | Helen A. Brough | Luisa Brussino | Moises A Calderon | Luis Caraballo | Victoria Cardona | Pedro Carreiro‐Martins | Tomas Casale | Lorenzo Cecchi | Alfonso M Cepeda Sarabia | Ekaterine Chkhartishvili | Derek K Chu | Ieva Cirule | Alvaro A Cruz | Wienczyslawa Czarlewski | Stefano del Giacco | Pascal Demoly | Philippe Devillier | Dejan Dokic | Stephen L Durham | Motohiro Ebisawa | Yehia El‐Gamal✝ | Regina Emuzyte | Amiran Gamkrelidze | Jean Luc Fauquert | Alessandro Fiocchi | Wytske J Fokkens | Joao A Fonseca | Jean‐François Fontaine | Radoslaw Gawlik | Asli Gelincik | Bilun Gemicioglu | Jose E Gereda | Roy Gerth van Wijk | R Maximiliano Gomez | Maia Gotua | Ineta Grisle | Maria‐Antonieta Guzmán | Tari Haahtela | Susanne Halken | Enrico Heffler | Karin Hoffmann‐Sommergruber | Elham Hossny | Martin Hrubiško | Carla Irani | Juan Carlos Ivancevich | Zhanat Ispayeva | Kaja Julge | Igor Kaidashev | Omer Kalayci | Musa Khaitov | Ludger Klimek | Edward Knol | Marek L Kowalski | Helga Kraxner | Inger Kull | Piotr Kuna | Violeta Kvedariene | Vicky Kritikos | Antti Lauerma | Susanne Lau | Daniel Laune | Michael Levin | Desiree E Larenas‐Linnemann | Karin C Lodrup Carlsen | Carlo Lombardi | Olga M Lourenço | Bassam Mahboub | Hans‐Jørgen Malling | Patrick Manning | Gailen D Marshall | Erik Melén | Eli O Meltzer | Neven Miculinic | Branislava Milenkovic | Mostafa Moin |

This Pocket Guide was developed by an ARIA and EAACI joint study group from a background paper of the ARIA-MASK study group and from the EAACI guidelines on allergen immunotherapy. Bousquet J, Pfaar O, Togias A, et al. (2019) AIT is a proven therapeutic option for the treatment of allergic rhinitis, conjunctivitis, and/or asthma using sublingual (SLIT) or subcutaneous (SCIT) routes.
However, AIT is more expensive than symptomatic treatments for allergic diseases (excluding biologicals). It is justified (i) in patients with rhinitis otherwise uncontrolled by symptomatic treatment or (ii) as an add-on to regular asthma treatment in controlled or partiallycontrolled asthmatic patients sensitised to house dust mites aiming to decrease asthma exacerbations, rescue and controller medication, and to improve quality of life.
Care pathways are structured multi-disciplinary care plans detailing the key steps of patient care. They promote the translation of guideline recommendations to their application in clinical practice.
Although many international and national AIT guidelines have been produced, this is the first care pathway for AIT. This pocket guide applies to sublingual (SLIT) and sub-cutaneous (SCIT) immunotherapy for allergic rhinitis.
It has been revised by members from 65 countries ( Figure 1).

| ALLERGENS TO BE ADMINISTERED
The decision to prescribe AIT should be based on relevant symptoms during allergen exposure, demonstration of sensitisation to the relevant allergens, and availability of good-quality extracts with proven efficacy and safety. Some allergen extracts are approved for marketing in the EU (list in annex) with some others also approved by national health agencies.
For certain products, efficacy and safety have been demonstrated in appropriate clinical studies on adults and children. The extrapolation to untested products, allergens or a different population from the one evaluated in the trial is not appropriate and not in line with current guidelines as there is no class-effect in AIT.
Both monosensitised and polysensitised patients can be treated.
However, in the latter case, the most clinically relevant allergen(s) should be used when symptoms are clearly present with allergen source exposure and when allergy tests confirm clinical findings.

| STRATIFICATION OF ALLERGIC PATIENTS
Precision medicine aims at the customisation of healthcare, tailored to the characteristics of each individual patient. The stratification of patients into subpopulations is the basis of clinical decision making ( Figure 2).
In allergic diseases, patient stratification is required to: � Propose the appropriate pharmacotherapy.
� Identify the most suitable candidates for AIT.
� Reduce the amount of time and resources needed to match the right patient to an optimal care management programme.
� Optimise costs as expensive therapeutic interventions are not necessary or suitable for all patients.
Patient stratification may also help to improve the patient's engagement.  6. The patient's (and caregiver's) views represent an essential component.

| Biomarkers
There are currently no in vivo or in vitro biomarkers validated for monitoring the efficacy of AIT although several potential candidates are currently being investigated.

| RHINITIS (WITH OR WITHOUT CONJUNCTIVITIS) IN ADOLESCENTS AND ADULTS
The selection of pharmacotherapy and AIT for patients with AR and/or allergic conjunctivitis may be better supported by evidence algorithms to aid patients and healthcare professionals jointly determine the treatment and its step-up or stepdown strategy depending on rhinitis control (shared decisionmaking).
A simple algorithm is proposed as an aid for physicians to determine the treatment of their patients (Figure 3).

| Treatment algorithm using visual analogue scale (VAS)
In the case of remaining ocular symptoms, add intra-ocular treatment.

| RHINITIS (WITH OR WITHOUT CONJUNCTIVITIS) IN CHILDREN
AIT is effective, has long-term beneficial effects after cessation, and may delay or prevent the onset of asthma. AIT can be initiated in children with moderate/severe rhinitis that is not controlled by appropriate medications according to guidelines.

| ASTHMA
An algorithm for HDM-driven allergic asthma diagnosis and management is proposed by the EAACI guidelines.
For patients with concomitant allergic rhinitis and sensitised to house dust mite-with persisting asthma symptoms despite lowmoderate dose of inhaled corticosteroids-SLIT can be considered, provided FEV1 is >70% predicted.
House dust mite SLIT should initially be considered as an addon therapy to controller treatment, and reduction in asthma controllers should be performed gradually under the supervision of a physician.
Immunotherapy is not indicated for the treatment of acute exacerbations, and patients must be informed of the need to seek medical attention immediately if their asthma deteriorates suddenly ( Figure 4).

| MULTIMORBIDITY
One strength of AIT is that it has the potential to control all allergic diseases related to a specific allergen, including rhinitis, conjunctivitis and asthma. Severe bronchospasm can also occur, especially in patients where asthma is not controlled.

| Sublingual immunotherapy (SLIT)
Allergen drops or tablets have a more favourable safety profile than injections. The initial dose should be performed in the doctor's surgery, and patients are advised to remain in the surgery for at least 30 min F I G U R E 4 Algorithm for AIT in asthma BOUSQUET ET AL.
-9 of 11 after administration. Thereafter, SLIT can be administered at home once the first dose has been given under the supervision of a physician.
Allergic reactions: The majority of patients will experience mild local reactions of the oropharyngeal passage. This is usually controlled by predosing with an antihistamine 30 min before the administration of SLIT. Sometimes, sneezing, nasal congestion or hives can occur. Anaphylaxis is rarely described.
In some countries, SLIT tablets include a warning about possible severe allergic reactions, and adrenaline auto-injectors are routinely recommended. This is not the case in Europe.

CONFLICT OF INTEREST
IAgache is an Associate Editor Allergy and CTA.