Adherence and Quality of Life Assessment in Patients With Asthma Treatment With Budesonide/Formoterol via the Elpenhaler Device

The COMPLETE Study

Konstantinos P. Exarchos; Nikoletta Rovina; George Krommidas; Dimitrios Latsios; Athena Gogali; Konstantinos Kostikas

Disclosures

BMC Pulm Med. 2022;22(254) 

In This Article

Results

Baseline Demographics and Clinical Characteristics

The study included 53 sites in Greece, which overall enrolled 716 patients. There were no patients excluded from the analysis, thus the study population analyzed was equal to 716 patients. The follow-up visits were performed at 3 and 6 months, where 684 (95.5%) and 666 (93%) patients completed each visit, respectively. Otherwise, there were no missing values, therefore, no imputation methods were applied. Amongst the 716 patients included in the study, 455 were women (63.5%), and 99.6% were of white race. Mean age was 52 years with 39% of the patients being 40–59 years. The median body mass index (BMI) of patients in the study was approximately 28, a rate indicating that the majority of patients had increased body weight. In addition, approximately half of the study patients were of higher education (Table 1).

In this study, 59.1% of the patients were non-smokers. 20.1% were ex-smokers with median pack-years equal to 20, while 149 patients (20.8%) were active smokers with median pack-years equal to 15. 42 out of the 149 smokers (28.2%) stopped smoking during the study, decreasing the number of smokers to 107 (15%).

The asthma treatment of the enrolled patients prior to the study is depicted in Figure 1; 59.4% of the patients were treatment-naive, while 291 patients (40.6%) had at least one past asthma treatment, with 180 patients having received 2 treatments. The most common past asthma treatment seemed to be a fixed combination of inhaled corticosteroids and LABA (128 patients). Note also that approximately 15.4% of the study patients had previously received concomitant asthma-related medications with 68 out of them (61.8%) having received leukotriene receptor antagonists (LTRA); 57.5% of the patients had not received any on-demand treatment until the day of enrollment.

Figure 1.

Past treatment for asthma (until the day of enrollment)

Medication Adherence

The mean (SD) MMAS-8 score at month 3 and 6 was 6.59 (1.74) and 6.85 (1.54) respectively. We observed a statistically significant increase of 0.20 (95%CI 0.08–0.32) units (p = 0.001) in MMAS-8 score at 6 months from Visit 1 (Month 3). The MMAS-8 scores for each patient were also categorized into "HA = high adherence" (score = 8), "MA = medium adherence" (score = 6–7.99), and "LA = low adherence" (score = 0–5.99). The specific proportions of patients in the 3 categories are presented in Table 2.

As shown in Figure 2, approximately 80% of the patients showed medium to high adherence (MMAS-8 score ≥ 6) throughout the study, however the patients in this category differed significantly between 3 and 6 months (McNemar's test p < 0.0001). More specifically:

Figure 2.

Adherence to treatment, as assessed by MMAS-8 scale at 3 and 6 months

There were 91 out of 183 patients (49.7%) changing from low to medium (55 patients) and high adherence (36 patients).
There were 71 out of 227 patients (31.3%) changing from medium to high adherence.
[The Morisky Widget, MMAS-8. MMAS-4 are protected by US and International Trademark and Copyright laws. Permission for use is required. A license agreement is available from: MMAS Research LLC 14,725 NE 20th St. Bellevue WA 98007].

Quality of Life

The total Mini AQLQ score and individual domain scores are presented in Figures 3a–e. Specifically, Figure 3a depicts the total Mini AQLQ score. The mean (SD) total score was 4.37 (1.13), 6.00 (0.77) and 6.34 (0.62) at baseline, 3 months and 6 months respectively and the change from baseline was 1.66 (95%CI 1.58, 1.74) and 2.01 (95%CI 1.93–2.10) units at 3 and 6 months, respectively (p < 0.0001 for both comparisons), indicating that the quality of life of the patients was improved overall at the end of the study.

Figure 3.

a Total Mini AQLQ score. b Symptoms domain score from the Mini AQLQ score. c Environment domain score from the Mini AQLQ score. d Emotions domain score from the Mini AQLQ score. e Activities domain score from the Mini AQLQ score

Figures 3b–e show the individual scores for the 4 domains (symptoms, environment, emotions and activities, respectively). Specifically, for the Symptoms domain score the change from baseline was 1.96 (95%CI 1.87, 2.05) and 2.36 (95%CI 2.26, 2.45) units at 3 and 6 months; for the Activities domain score the change from baseline was 1.25 (95%CI 1.16, 1.35) and 1.51 (95%CI 1.41, 1.62) units at 3 and 6 months, respectively; for the Emotions score the change was 1.63 (95%CI 1.53, 1.73) and 1.98 (95%CI 1.87, 2.09) units; and as for the Environment domain score the change from baseline was 1.73 (95%CI 1.64, 1.82) and 2.15 (95%CI 2.05, 2.24) units at 3 and 6 months. It should be noted that for all aforementioned comparisons p < 0.0001. The highest score amongst all domains was the activities domain score which was the highest throughout the study, with a median score at 6 months equal to 6.75. Nevertheless, the median score of the aforementioned domain at the end of the study was 6, significantly increased by 2.15 units from baseline (p < 0.0001).

Quality of life of the study patients was also evaluated by the Mini AQLQ at 3 and 6 months per treatment adherence group during the same months (data not shown). Overall, almost all mean scores per question were higher or equal at 3 months for the patients with medium adherence to study treatment. Social activities were scored the highest amongst all questionnaire items for every treatment adherence group. Regarding the 6-month assessment of the Mini AQLQ, all mean scores were slightly higher than in 3 months, thus, the quality of life of patients with low, medium and high adherence was improved. Overall, high adherence patients showed greater improvement in their quality of life compared to low and medium adherence groups, having the highest scores per domain and in total across the three visits (Figure 4).

Figure 4.

Change in Mini AQLQ score in the three consecutive visits, per adherence group

Moreover, we have assessed the difference of Mini AQLQ scores in total as well as in each domain, per adherence group (Figure 5). We observed that the high adherence group had the greatest improvement in their quality of life compared to medium and low adherence groups, as shown in the Mini AQLQ scores per each domain (symptoms, activities, emotions, and environment) and in total.

Figure 5.

Mini AQLQ scores in total as well as in each domain, per adherence group

Spirometric Results

The effectiveness of the FDC budesonide/formoterol treatment via the Elpenhaler device was evaluated by spirometry data at baseline, 3 months and 6 months. The mean (SD) FEV1 was 2.58 L (0.85) at the end of the study, increased by 220 mL from baseline. More specifically, for the low adherence group the mean (SD) FEV1 in L across all 3 visits was 2.42 (0.87) L, 2.68 (0.89) L and 2.59 (1.09) L; for the medium adherence group the mean (SD) FEV1 was 2.32 (0.91) L, 2.57 (0.90) L, 2.57 (1.09) L; and for the high adherence group the respective values were 2.35 (0.88) L, 2.52 (0.91) L, and 2.57 (0.86) L.

We examined the changes in spirometry for each adherence group, based on MMAS-8. We observed a slight drop in FEV1 measured from 3 to 6 months only for the low adherence patients. In the medium adherence group the mean FEV1 measured increased from baseline to 3 month visit and remained unchanged in the 6 month visit. As for the high adherence group we observe a gradual increase from baseline to 3 month visit and subsequently to the 6 month visit. Moreover, change from baseline at 6 months was lower in low adherence patients than in medium and high adherence patients (170 mL versus 250 mL and 220 mL, respectively). The minimal clinically important difference in patients with asthma according to a US NIH report suggests that changes of 100–200 mL are likely to be clinically important.[25] The fact that there was such an improvement in FEV1 in all groups, but the mean improvement was higher in the medium and high adherence groups, suggests that all patients received an effective treatment, however, the improvement in lung function was more prominent in those with better adherence. The change on FEV1 measured in L across all visits per adherence group is shown in Figure 6.

Figure 6.

Change on FEV1 measured (L) across all visits, per adherence group

Exacerbations and Safety

Regarding asthma exacerbations, 30 (4.4%) and 26 (3.9%) of the patients had at least one asthma-related exacerbation during 3 and 6 months of the study respectively. Of the 30 patients who experienced an exacerbation during the first 3 months of the study, 18 had their treatment modified and 1 patient discontinued. Moreover, 13 (43.3%) and 11 patients (42.3%) reported that they had received oral corticosteroids for their exacerbations at Visits 1 and 2 respectively. None of the patients was hospitalized due to an exacerbation throughout the study period.

The safety of the treatment under consideration was assessed in terms of adverse events and severe adverse events. Overall, only 4 patients (0.6%) had at least one adverse event throughout the study period; none of the patients had a severe adverse event. Two patients (0.3%) discontinued the initial treatment permanently due to an adverse event, while 3 patients (0.4%) had a dose decrease. The most common adverse event was tachycardia, which occurred in 2 patients.

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