Medication adherence to inhalation therapy and the risk of COPD exacerbations: a systematic review with meta-analysis

Assessing medication adherence is crucial in chronic obstructive pulmonary disease (COPD) management to prevent exacerbations. However, it is unclear whether this association between adherence and exacerbations is influenced by the adherence assessment methods or thresholds used. Electronic healthcare databases are valuable to study exacerbations and adherence in real life. We aimed to systematically review the literature to identify adherence assessment methods and thresholds used in healthcare databases when investigating the association between medication adherence and COPD exacerbations and to meta-analyse the associated effect sizes.

MEDLINE, Web of Science and Embase were searched for peer-reviewed articles, written in English, published up to 10 October 2022 (PROSPERO: CRD42022363449). Two reviewers independently conducted screening for inclusion and performed data extraction. A qualitative approach described the adherence assessment methods and thresholds used. A quantitative approach (meta-analysis using random effects model) estimated the association between adherence and the risk of COPD exacerbations.

Eight studies were included in the systematic review of which five studies were included in the meta-analysis. The medication possession ratio (MPR) and the proportion of days covered (PDC) were the adherence assessment methods used and 0.80 was always used as threshold to differentiate good from poor adherence. Adherence and exacerbations were mostly measured over the same time period. Poor adherence (MPR or PDC<0.80) was significantly associated with a higher COPD exacerbation risk (OR 1.40, 95% CI 1.21 to 1.62, I²=85%), regardless of the adherence assessment method used. Results were consistent when stratified by exacerbation severity. Poor adherence was also associated with a time-dependent risk of COPD exacerbations (incidence rate ratio 1.31, 95% CI 1.17 to 1.46).

Our systematic review with meta-analysis demonstrated a 40% increased risk of COPD exacerbations in case of poor adherence to inhaler medication.

CRD42022363449.