Digital interventions to improve adherence to maintenance medication in asthma

Background Asthma is the most common chronic lung condition worldwide, affecting 334 million adults and children globally. Despite the availability of effective treatment, such as inhaled corticosteroids (ICS), adherence to maintenance medication remains suboptimal. Poor ICS adherence leads to increased asthma symptoms, exacerbations, hospitalisations, and healthcare utilisation. Importantly, suboptimal use of asthma medication is a key contributor to asthma deaths. The impact of digital interventions on adherence and asthma outcomes is unknown. Objectives To determine the effectiveness of digital interventions for improving adherence to maintenance treatments in asthma. Search methods We identified trials from the Cochrane Airways Trials Register, which contains studies identified through multiple electronic searches and handsearches of other sources. We also searched trial registries and reference lists of primary studies. We conducted the most recent searches on 1 June 2020, with no restrictions on language of publication. A further search was run in October 2021, but studies were not fully incorporated. Selection criteria We included randomised controlled trials (RCTs) including cluster- and quasi-randomised trials of any duration in any setting, comparing a digital adherence intervention with a non-digital adherence intervention or usual care. We included adults and children with a clinical diagnosis of asthma, receiving maintenance treatment. Data collection and analysis We used standard methodological procedures for data collection. We used GRADE to assess quantitative outcomes where data were available. Main results We included 40 parallel randomised controlled trials (RCTs) involving adults and children with asthma (n = 15,207), of which eight are ongoing studies. Of the included studies, 30 contributed data to at least one meta-analysis. The total number of participants ranged from 18 to 8517 (median 339). Intervention length ranged from two to 104 weeks. Most studies (n = 29) reported adherence to maintenance medication as their primary outcome; other outcomes such as asthma control and quality of life were also commonly reported. Studies had low or unclear risk of selection bias but high risk of performance and detection biases due to inability to blind the participants, personnel, or outcome assessors. A quarter of the studies had high risk of attrition bias and selective outcome reporting. We examined the effect of digital interventions using meta-analysis for the following outcomes: adherence (16 studies); asthma control (16 studies); asthma exacerbations (six studies); unscheduled healthcare utilisation (four studies); lung function (seven studies); and quality of life (10 studies). Pooled results showed that patients receiving digital interventions may have increased adherence (mean difference of 14.66 percentage points, 95% confidence interval (CI) 7.74 to 21.57; low-certainty evidence); this is likely to be clinically significant in those with poor baseline medication adherence. Subgroup analysis by type of intervention was significant (P = 0.001), with better adherence shown with electronic monitoring devices (EMDs) (23 percentage points over control, 95% CI 10.84 to 34.16; seven studies), and with short message services (SMS) (12 percentage points over control, 95% CI 6.22 to 18.03; four studies). No significant subgroup differences were seen for interventions having an in-person component versus fully digital interventions, adherence feedback, one or multiple digital components to the intervention, or participant age. Digital interventions were likely to improve asthma control (standardised mean difference (SMD) 0.31 higher, 95% CI 0.17 to 0.44; moderate-certainty evidence) - a small but likely clinically significant effect. They may reduce asthma exacerbations (risk ratio 0.53, 95% CI 0.32 to 0.91; low-certainty evidence). Digital interventions may result in a slight change in unscheduled healthcare utilisation, although some studies reported no or a worsened effect. School or work absence data could not be included for meta-analysis due to the heterogeneity in reporting and the low number of studies. They may result in little or no difference in lung function (forced expiratory volume in one second (FEV1)): there was an improvement of 3.58% predicted FEV1, 95% CI 1.00% to 6.17%; moderate-certainty evidence); however, this is unlikely to be clinically significant as the FEV1 change is below 12%. Digital interventions likely increase quality of life (SMD 0.26 higher, 95% CI 0.07 to 0.45; moderate-certainty evidence); however, this is a small effect that may not be clinically significant. Acceptability data showed positive attitudes towards digital interventions. There were no data on cost-effectiveness or adverse events. Our confidence in the evidence was reduced by risk of bias and inconsistency. Authors' conclusions Overall, digital interventions may result in a large increase in adherence (low-certainty evidence). There is moderate-certainty evidence that digital adherence interventions likely improve asthma control to a degree that is clinically significant, and likely increase quality of life, but there is little or no improvement in lung function. The review found low-certainty evidence that digital interventions may reduce asthma exacerbations. Subgroup analyses show that EMDs may improve adherence by 23% and SMS interventions by 12%, and interventions with an in-person element and adherence feedback may have greater benefits for asthma control and adherence, respectively. Future studies should include percentage adherence as a routine outcome measure to enable comparison between studies and meta-analysis, and use validated questionnaires to assess adherence and outcomes.