Introduction

AIT is the only treatment option that targets the underlying pathophysiology of allergy and therefore shows disease-modifying effects (1,2). A number of randomized controlled trials (RCTs) demonstrated long-term clinical efficacy persisting for years after treatment discontinuation (3,4). There is also evidence that AIT can prevent the development of new sensitizations and reduce the risk of subsequent asthma development in patients with AR (5).
In 1964, the first randomized, double-blind, placebo-controlled study using subcutaneous immunotherapy (SCIT) for the treatment of IgE-mediated allergies to inhalant allergens was conducted (6). Starting from that point, many RCTs proved efficacy and safety for several seasonal and perennial allergens in allergic rhinitis/rhinoconjunctivitis and/or asthma (1,2,7,8).
RCTs are still considered as best and most reliable way to assess the efficacy and safety of an AIT product. The majority of statements in clinical guidelines are given on the basis of results received from RCTs. One key feature of RCTs is that they include an ‘ideal’ study population because they follow strict inclusion and exclusion criteria and study protocols. Thus they inevitably lack external validity since extrapolations to patients in real life are difficult. In contrast, real-world data (RWD) analyses include higher patient numbers using variable treatment patterns and a wide range of different alternative interventions applied by many physicians in daily practice (9). RWD can focus on the epidemiology, effectiveness, safety, medication adherence or cost of treatment related to a single drug or drug class but also provide long-term follow-up data beyond the time horizon observed in RCTs (9). These can be derived from different sources such as patient registries, health care databases, electronic health records, patient networks, and patient‐generated data from wearables. Patient registries collecting data prospectively, in a cohesive way, with using standardized protocols are proposed to provide a higher quality of evidence than those collected retrospectively (10). All RWD can serve as a basis for real-world evidence (RWE) and provide additional insights into a patient’s health status or use of drugs to supplement RCTs (11).
Concerning the assessment of both, RCT data and RWD in AIT, the aspect of different application routes - subcutaneous (SCIT) and sublingual (SLIT) tablets or drops – has to be considered. The underlying immune modulating mechanisms are slightly different (12,13). In addition, there are many different products on the market which differ in the allergen extract used, manufacturing process, doses, and dosing regimens. Taking this into consideration, the broad diversity of AIT products requires the proof of efficacy for each individual product in RCTs which also applies for RWE with regard to effectiveness.
This review focuses on analysis of retrospective multicentre database real-world evidence studies on AIT preparations with respect to long-term effectiveness and medication adherence. The chosen studies are ranked a middle quality in the hierarchy of AIT in real-world evidence proposed in an EAACI position paper in 2021 (10).