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.