Literature
Search
The literature search in PubMed resulted in 13 publications (14–26).
For key characteristics of the studies see Tables S1 (grass pollen
studies), S2 (tree pollen studies), S3 (house dust mite (HDM) studies)
and S4 (studies not differentiating between allergens) in supplementary
information. Some analyses were funded by manufacturers of AIT
preparations like the ReWARD (Real World Evidence in Allergy Research
and Development) program by Allergopharma GmbH & Co. KG, Germany
(14,15,17), the BREATH (Bringing Real-World Evidence to Allergy
Treatment for Health) program by Stallergenes Greer, France
(18,19,21,22) with Devillier et al. 2017 (22) representing a subanalysis
of Zielen et al. (21) and the REACT (Real world effectiveness in allergy
immunotherapy) study by ALK-Abelló, Denmark (25). ALK-Abelló, Denmark
supported two further studies (16,26). Additionally, there are three
publications focussing on medication adherence; one each initiated by
ALK-Abelló (20) and Stallergenes Greer (23), while no company funding is
mentioned in the third one (24).
The analyses were carried out using retrospective prescription databases
from
- IMS LRx, IQVIA, Germany, formerly named LRx, IMS Health, covering
about 60% of the statutory healthcare prescriptions in Germany
(14,15,17,19,21,22),
- IQVIA France covering 34% of the nationwide retail pharmacies (18),
- AOK Plus Saxony, a regional sick fund, covering 55% of the population
from the federal state of Saxony, Germany (16,26),
- Betriebskrankenkasse (BKK), Germany, a branch of the statutory health
insurance including approx. 9 million patients (25),
- the German IMS Health Disease Analyzer database which is derived from
electronic medical records from a panel of German general
practitioners and other office-based, specialist physicians: The
coverage comprised 13.4 million patients during the analysis period
(20),
- PHARMO Record Linkage system, a network of linked databases providing
drug-dispending records from community pharmacies from the Netherland
which covered roughly one eighth of the total Dutch population (24),
- Patient Tracking National database provided by INSIGHT Health GmbH,
Germany (23).
The data mostly include demographic information (sex and age) and
information related to prescriptions, e.g. product, pack size, pack
count and prescriber. Diagnoses according to the International
Statistical Classification of Diseases and Related Health Problems-10
(ICD-10) codes were available in three studies (16,25,26).
Each of the studies listed has defined exclusive inclusion and exclusion
criteria, which may be found in the respective original publications.
The 13 publications presented data on effectiveness and/or medication
adherence for AIT in general, preparation groups or single SCIT and SLIT
products. Some of the assessments focused on certain allergens (grass
pollen, tree pollen, house dust mites), while others did not.
Most of the assessments investigating effectiveness of AIT consistently
predefined different time intervals before (pre-index period), during
(treatment period) and after AIT application (follow-up period)
(15,17–19,21,22). In other assessments, the whole period after
receiving the first AIT prescription was designated as follow-up period
(16,25,26).
Effectiveness of AIT was calculated by comparison to a Non-AIT control
group receiving prescriptions of symptomatic medication for the
treatment of AR and/or anti-asthmatic medication for the treatment of
asthma.
Non-AIT control patients were matched with patients receiving AIT in
order to minimize confounding bias. An ‘exact matching’ method was
conducted in 6 studies (15,17–19,21,22) on the basis of several
variables, e.g. age class, sex and asthma status. In one analysis
‘propensity score matching’ was performed (25).
In this overview, we focus on data concerning the long-term
effectiveness of AIT, i.e. during the full analysis period (treatment
plus follow-up period) and follow-up periods as well as medication
adherence.
1) Long-term effectiveness of AIT was evaluated by means of the
following endpoints:
- progression of allergic rhinitis: based on a comparison of the number
of prescriptions for symptomatic treatment of AR (e.g. nasal
corticosteroids, antihistamines) with or without allergic
conjunctivitis during follow-up vs. pre-index compared to a Non-AIT
group receiving only anti-symptomatic treatment.
- progression of asthma in patients with asthma at pre-index period:
based on a comparison of the number of prescriptions for asthma
medication (e.g. long-acting beta-agonists (LABAs), inhaled
corticosteroids (ICSs), combinations of LABAs and inhaled
corticosteroids (ICSs), methylxanthines, leukotriene antagonists,
short-acting beta-agonists (SABAs)) in AIT-treated vs. Non-AIT control
patients.
- incidence of asthma in patients without asthma at pre-index period:
development of asthma based on prescriptions for anti-asthmatic
medication compared to the Non-AIT control group.
- time to onset of asthma after starting AIT.
2) Medication adherence to AIT was evaluated based on different
definitions: adherence, compliance, persistence and/or days on therapy.