Impact of an electronic monitoring intervention for improving adherence to inhaled therapy in patients with asthma and COPD

Asthma bronchiale and chronic obstructive pulmonary disease (COPD) are two of the leading chronic respiratory diseases worldwide and associated with high morbidity, mortality, and a major economic burden. Despite progress in pharmacological and non-pharmacological treatment in recent years, the burden of disease among asthma and COPD patients is high. Reasons for uncontrolled diseases are manifold, but are often associated with poor inhalation technique and non-adherence to the prescribed treatment plan. As observed in many chronic diseases, poor adherence to medication is also a common phenomenon among asthma and COPD patients. This causes deterioration of symptoms and recurrent exacerbations resulting in increased rates of morbidity, physician visits, hospitalizations, mortality, reduced quality of life, and increased healthcare expenditures. However, it has been demonstrated that the frequency of exacerbation can be reduced by the administration of certain medication. Furthermore, high adherence is associated with reduced exacerbation rates in patients with asthma and COPD.
As outlined above, maintaining adequate adherence to inhaled medication is of major importance for achieving therapeutic success, in particular for the treatment of chronic diseases. Different interventions and strategies are already described in the literature aiming to enhance adherence. The greatest success was attained with complex interventions combining several strategies. Nevertheless, to date no intervention was determined to be particularly successful.
Therefore, this thesis aims to contribute to this challenging but important research field by investigating the impact of two simple interventions on adherence to inhaled therapy in patients with asthma and COPD.
Prior to the study start, we provided a training course for each participant regardless of the treatment group to guarantee a comparable level of disease knowledge and inhalation technique. Further, each patient was equipped with an electronic monitoring device, which was used as the method of choice for the assessment of objective adherence. Overall, the performed intervention consisted of a reminder in form of phone calls and a daily alarm clock as well as feedback on patients’ individual adherence profile. The combination of these two common types of interventions has been chosen since they appeared to be easily applicable in daily clinical practice. We considered this to be one of the important factors in order to guarantee an efficient improvement of patients’ adherence.
By the intervention, we expected a prolongation of time to next exacerbation, which was defined as the primary endpoint of this study. Moreover, we assumed an improvement of patients’ taking and timing adherence as well as quality of life, determined as the two secondary endpoints.
The thesis is divided into the following three parts:
The aim of Part I was to design and write a study protocol taking into account the above-mentioned aims and under consideration of the current state of the literature as well as the studies already conducted in this field.
Part II describes a cross-sectional analysis to evaluate baseline data on compliance in accordance with current treatment guidelines (Global Initiative for Asthma (GINA) and Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines). Furthermore, baseline data is provided on inhaler application after a training course and its impact on quality of life and symptom control in a typical population with chronic lung diseases from the Adherence-Trial. Overall, correct inhalation technique ranged from 55% to 100% depending on the type of inhaler. 112 participants (68%) participants were treated corresponding to the global guidelines. COPD patients with incorrect device application had a higher CAT sum score compared to those with a correct device application (p=.02). Moreover, COPD patients with incorrect device application had to cough more often (p=.03) and were more breathless while walking up hills or one flight of stairs (p=.02). While there was no significance to be found in asthma patients, COPD patients who used their devices correctly had a significantly better mean FEV1% predicted at baseline compared to those who applied their devices incorrectly (p=.04).
In the last part of this thesis (Part III), time to next exacerbation - the primary endpoint of the study - was evaluated and compared between the intervention and the control group. Furthermore, the objective adherence was analyzed by evaluating the taking and timing adherence, as well as the gaps during the study period. Patients’ quality of life was assessed by the St. George Respiratory Questionnaire (SGRQ). Time to next exacerbation was longer (172 days [95% CI, 161 to 182] vs. 161 days [95% CI, 149 to 174], p=.27) and the risk for experiencing an exacerbation lower (HR, 0.67 [95% CI, 0.36 to 1.33], p=.14) in the intervention compared to the control group, but failed to reach statistical significance. In the intervention group significantly more days with a taking adherence between 80-100% were observed with both inhalation techniques (puff inhalers: 81.6±14.2 vs.60.1±30.3, p<0.001; dry powder capsules: 89.6±.9.8 vs. 80.2±21.3, p=.01). Timing adherence with regard to the use of puff inhalers was significantly higher in the intervention compared to the control group (68.9±25.0 vs. 50.6±32.5, p<.001) while there was a trend towards improved timing adherence for dry powder capsules (79.6±12.6 vs. 71.7±22.0, p=.052). However, no effects on health-related quality of life were observed (p>.05).
In conclusion this thesis showed:
•At baseline, a large number of the participating asthma, COPD or asthma-COPD overlap patients were treated on target based on the GINA and GOLD guidelines valid at the time of the patient’s inclusion into the Adherence-Trial.
•Correct handling of inhaler devices was largely dependent on the device used. In the Adherence-Trial population, metered dose inhalers were applied more frequently in an incorrect way compared to dry powder inhalers. This particularly applies to the Ellipta® device, which has just recently been introduced to the market and which showed a very good applicability.
•A correct inhalation technique of the prescribed medication had a positive impact on the health status and the lung function of COPD patients. This was achieved by a comprehensive training of correct inhalation technique.
•Regular, automatic and personal reminders seem to have caused a significant improvement in taking and timing adherence with regard to the inhalation with puff inhalers and dry powder capsules. Moreover, reminders can help to avoid forgetting the inhalation of the prescribed medication. Patients who experienced support in their adherence had significantly fewer days without inhalation and fewer gaps over several consecutive days compared to patients receiving no support.
•Regular, automatic and personal reminders, led to a substantial improvement in patients’ adherence to inhaled medication. However, this was not associated with an improvement in health-related quality of life in patients with chronic airway diseases.
•Higher adherence to the prescribed medication plan was not only associated with a trend towards longer time to next exacerbation but also with a reduced risk of experiencing an exacerbation.