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Adherence to CF treatment can be improved with the right approach!

The burden of routine, daily therapies prescribed for people with cystic fibrosis (CF) is large. Maintaining adherence to such chronic therapies can be challenging, especially when the financial costs are considerable and they are time consuming, though nonadherence is associated with poor health outcomes. Therefore, efforts to improve adherence in people with CF are important, as reflected by the recent global James Lind Alliance Priority Setting Partnership exercise where finding ways to help people with CF to ‘improve and sustain adherence to treatment’ was identified as a priority for the CF community. Factors influencing adherence are complex. Nonadherence can be intentional or nonintentional. Patientrelated factors include individuals’ understanding of their disease, beliefs about the effectiveness of specific treatments and side effects, and the presence or absence of good medication routines. External factors that affect adherence include complexity of dosing regimens, cultural factors and the cost of treatments. For people with CF, the reality of living with a chronic disease and having to adhere to complicated treatment regimens inevitably competes with other life demands and even fatigue. Hence, to date, most efforts to improve adherence in CF have failed to have a sustained positive effect. In this edition of Thorax, Wildman and colleagues show that adherence to chronic CF therapies can be improved over sustained periods. They conducted a twoarm, openlabel, parallelgroup, usual carecontrolled randomised clinical trial at 19 CF centres in the UK to study the effect of a multicomponent intervention to support adherence to inhaled therapies in people with CF older than 16 years of age. The study of adherence to inhaled therapies is particularly interesting as patients with CF and their families rank inhaled therapies, an important component of the treatment regimen for many people with CF, as burdensome. Over 600 participants were recruited. The intervention can briefly be described as regular, adaptable occasions of behaviour therapy with specially trained CF clinicians with the intention to improve adherence to inhaled treatments augmented by an online platform that provided participants with realtime, objective data on their adherence, and tailored information to participants. Adherence was measured electronically by a data logger—the gold standard for measuring adherence. Over the 1year study period, adherence was significantly higher in the intervention group (52.9% vs 34.9%) and there was a reduction in perceived burden of treatment. Of note, in the clinical trial, there was no significant difference in the primary outcome measure, that is, rate of pulmonary exacerbations requiring intravenous antibiotics. However, the study was powered to detect a difference of 0.5 exacerbations over a year—a big ask when people with CF are hospitalised on average once a year for treatment of exacerbations. Notably, forced expiratory volume in one second (FEV1) per cent predicted in the control group dropped by 1.4 from 58.3 to 56.9, whereas FEV1 per cent predicted in the intervention group dropped only 0.1 from 60.7 to 60.6. As FEV1 per cent predicted in people with CF generally drops by approximately two points per year, the relatively small drop in the intervention group suggests that improved adherence slowed the progressive drop in lung function. Importantly, the improved adherence achieved by Wildman and colleagues was achieved through a very resourceintensive intervention. It is not likely that such a resourceintensive programme will be feasible in clinical care at many CF centres. A major strength of the research is that the intervention was designed and developed based on sound theoretical concepts. Now that the concept has been shown to work, the challenge will be to adapt the intervention into a more streamlined, less resourceintensive intervention, which can readily be incorporated into clinical care. Another way to potentially improve adherence in CF is to simplify treatment regimens. With potent CF modulator therapies becoming increasingly available, the ongoing need for use of other CF therapies is being questioned. The SIMPLIFY clinical trial will be the largest multicentre, randomised, controlled medicationwithdrawal study in CF to evaluate if other chronic CF medications can safely be discontinued. Similarly, the CF STORM trial (ISRCTN14081521), embedded within the UK CF Registry, will use a randomised controlled openlabel design to explore the reduction of nebulised mucoactive therapies after commencement of elexacaftor–tezacaftor–ivacaftor. Until the results of such trials can provide guidance, the large burden of chronic CF treatments will remain for many. Also, not all people with CF will qualify for potent modulator therapy, experience similar benefits or indeed tolerate therapy. Therefore, the need to address adherence to treatment will remain an important issue in CF. The study by Wildman and colleagues has implications not only for CF but also for other chronic diseases. First, efforts to improve adherence should be tailored to the individual. Given the complex nature of nonadherence, generic solutions will benefit some but not all. Second, the study highlights the importance of a wellinformed, comprehensive approach to overcoming barriers to adherence. Overcoming such barriers will greatly benefit patients who have to deal with chronic disease and associated treatments.