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).