**1. Introduction**

Allergic rhinitis and bronchial asthma are widespread diseases that can impact social life, school learning, and work productivity when poorly controlled by conventional therapy [1]. In addition, allergic rhinitis is considered one of the major risk factors for asthma, as up to 40% of patients with allergic rhinitis have or will go on to develop it [2]. Allergen immunotherapy (AIT) is the only disease-modifying treatment for allergic diseases, as it can prevent both the onset of new allergic sensitizations and disease progression [3]. AIT should be considered in those subjects with inadequate response or adverse effects to conventional medications such as antihistamines, topical intranasal antihistamines, and intranasal corticosteroid sprays [4–6]. Two routes of administration of AIT, subcutaneous (SCIT) or sublingual (SLIT), are currently used in clinical practice and have shown good efficacy in the treatment of allergic rhinitis and bronchial asthma [7]. International guidelines recommend that maintenance therapy for both SCIT and SLIT should be continued

**Citation:** Mormile, I.; Granata, F.; Detoraki, A.; Pacella, D.; Della Casa, F.; De Rosa, F.; Romano, A.; de Paulis, A.; Rossi, F.W. Predictive Response to Immunotherapy Score: A Useful Tool for Identifying Eligible Patients for Allergen Immunotherapy. *Biomedicines* **2022**, *10*, 971. https://doi.org/ 10.3390/biomedicines10050971

Academic Editor: Stanislawa Bazan-Socha

Received: 28 February 2022 Accepted: 20 April 2022 Published: 22 April 2022

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**Copyright:** © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

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for at least three years [4,6,7]. Hence, AIT is a long-lasting and expensive treatment, especially if the patient is being treated for more than a few allergens. In addition, in clinical studies, it has been frequently observed that a percentage of patients undergoing AIT do not have significantly beneficial effects [8]. Indeed, the efficacy of AIT ranges between 60% and 90% [9].

Several studies have tried to identify some biomarkers able to predict AIT response through the years. For instance, the assessment of serum-specific IgE [10] and the specific and total IgE ratio has been proposed as a biomarker of AIT efficacy [11]. Other studies suggested a possible correlation between some subtypes of IgG (IgG1, sIgG4) and clinical outcomes [12,13]. Finally, changes in cytokine pattern (e.g., IL-4, IL-13, IL-10) have been associated with AIT response [9,14,15]. However, there is no consensus on the use of these markers in the clinical routine.

The diagnostic approach to allergic disease has significantly been improved by the Component-Resolved Diagnosis (CRD), which provides information about patients' sensitization at the molecular component level by integrating the Skin Prick Test (SPT) and the specific IgE assay with extractive allergen results. Indeed, CRD can increase awareness about the major allergen sensitization and help avoid the administration of AIT for irrelevant allergens, improving its clinical efficacy and cost effectiveness [16,17]. However, the studies which tried to establish a direct link between CRD and AIT outcomes have shown conflicting results.

This study aims to develop and validate a disease score, referred to as Predictive Response to Immunotherapy Score (PRIS), combining clinical features and laboratory results to predict the likelihood of clinical improvement during AIT and identify eligible patients.
