Introduction
It is estimated that 3.2 million people die of asthma worldwide each
year and several independent reviews have highlighted that many of these
deaths are preventable(1, 2). Infrequent use of ICS and/or over-reliance
on SABA are recognised as key contributors to asthma-related morbidity
and mortality(1). In a landmark study published in 2000, Suissa and
colleagues found that the number of ICS canisters in the prior year
directly related to the risk of death from asthma(3). However, despite
this and similar reports, adherence to ICS remains poor. Even in the
context of the COVID-19 pandemic, ICS adherence rates averaged 55%
during 2020, with only 42% achieving the 75% threshold of good
adherence (4).
Adherence, often used synonymously
with compliance and concordance, refers to the extent to which the
recommendations made by a healthcare professional (HCP) regarding
medication are accepted and followed by the patient(5). The adherence
process comprises of three chronological phases; initiation,
implementation and persistence. Initiation is a binary variable,
patients either start taking their medication or do not. Implementation
refers to whether the dosing corresponds to the prescribed dosing
regimen. Lastly, persistence is from the time of initiation to its
discontinuation(6). Most measures of adherence reflect behaviour from a
few weeks to 12 months. Persistence over 12 months has been measured in
only one study thus far(7).
Non-adherence to medication is either intentional or unintentional.
Intentional non-adherence usually reflects a scenario where a patient
actively makes a decision to not follow the advise given and does not
take their prescribed medication(8). This may be due to concerns about
side effects, the possibility of addiction or a wish to simply not rely
on a medication. In contrast, unintentional non-adherence is where the
patient fully intends to be adherent to their treatment, but either
forgets to use it or due to poor inhaler technique, minimal drug reaches
the desired location(5, 8).
Adherence can be assessed in a number of ways, each with their
advantages and disadvantages (table 1). Critically, an ideal method of
adherence monitoring should be objective, accurate and unobtrusive to
minimise impact on patient behaviour(9). The most widely used adherence
measures are patient self-report upon direct questioning and written
questionnaires(8). Questionnaires can be useful in identifying barriers
to non-adherence, allowing for personalised interventions to be made.
Examples of these include the Medication Adherence Report Scale for
asthma (MARS-A)(10), Morisky Medical Adherence Scale (MMAS)(11) and the
Test of Adherence to Inhalers (TAI) questionnaire(12). However, these
subjective measures are not considered particularly robust as it is well
known that patients over-report their adherence(13).
The most common objective proxy, is use of the medication possession
ratio (MPR) or the proportion of days covered (PDC), using medication
issues as a determinant of adherence. This method has been found to be
useful and reasonably accurate(14). However, a secondary analysis of the
Salford Lung Study dataset, which included >4000 asthma
patients, found that over 30% of prescriptions issued were not
collected from the dispensary(15). This suggests that prescription
records are likely to be an over-estimation of actual adherence. Where
available, dose counters may also be used to determine adherence as long
as patients are on a fixed dose regimen(8).
The use of serum ICS concentration as a direct measure of adherence has
also been described in a small pilot study reporting very low ICS
concentration levels for patients with poor inhaler technique(16). More
recently, a larger study suggested that a positive result was
confirmation of short-term adherence only and other measures of
adherence would be required to confirm longer term ICS use (17).
Finally, over the last decade, some specialist asthma centres have
incorporated fractional exhaled nitric oxide (FeNO) suppression testing
into clinical practice to identify the clinical and biological response
to DOT with ICS. This method allows differentiation between those with
ICS-responsive, difficult-to-control but non-severe asthma, from
patients with ICS-resistant, severe asthma(18, 19). Although this has
been a huge step forward in both adherence monitoring and improved
identification of appropriate patients for biologic therapies, it is
both resource and time intensive for the patient and clinical team
alike.
Consequently, there has been a genuine appetite amongst the clinical
community caring for difficult-to-control asthma patients for a cheap,
simple, robust measure that can inform the HCP about ICS and SABA use,
whilst additionally offering reminders to the patient who is
unintentionally non-adherent. With this review we report on the most
promising of a new generation of EMDs that are currently emerging.
Together, they have the potential to transform the quality of asthma
care and significantly reduce asthma-related morbidity and mortality in
the coming years.