The impact of indacaterol/glycopyrronium fixed-dose combination versus tiotropium monotherapy on lung function and treatment preference: a randomized crossover study - the FAVOR study

Abstract

Background: The objective of the FAVOR study was to evaluate the effect of indacaterol/glycopyrronium (IND/GLY) versus tiotropium on peak forced expiratory volume in 1 s (FEV₁) and also to investigate patient satisfaction and treatment preference.

Methods: Patients with moderate-to-severe airflow limitation (FEV₁/forced vital capacity ratio of <0.70), those with a COPD assessment test score of ≥10, and those who were maintained on tiotropium HandiHaler^® therapy prior to enrollment were recruited for the study, and randomized (1:1) to receive either 4 weeks open-label IND/GLY (110/50 μg) once daily followed by 4 weeks of tiotropium (18 μg) once daily or vice versa. The primary endpoint was FEV₁ 1 h post-inhalation after 4 weeks of treatment. Other endpoints included patient's and physician's preference for treatment, patient's satisfaction evaluated using a study-specific questionnaire and the abbreviated Treatment Satisfaction Questionnaire for Medication, and safety and tolerability.

Results: Eighty-seven out of 88 randomized patients completed the study and showed significantly higher FEV₁ 1 h post-inhalation after 4 weeks of treatment with IND/GLY versus tiotropium (treatment difference =0.081 L; p=0.0017). IND/GLY was preferred over tiotropium among the patients (69.4% versus 30.6%, p=0.0004) and the physicians (81.6% versus 18.4%, p<0.0001). A higher proportion of the patients stated they were very satisfied or satisfied with IND/GLY versus tiotropium with regard to dyspnea reduction (79.3% versus 58.0%, respectively) and reduction of dyspnea on exertion (72.4% versus 43.2%, respectively). Patients treated with IND/GLY showed significant improvement in Treatment Satisfaction Questionnaire for Medication domain scores versus tiotropium. IND/GLY demonstrated a good safety and tolerability profile.

Conclusion: This study indicated that, beyond FEV₁, important patient-reported outcomes improved with the open-label dual bronchodilator IND/GLY when compared with tiotropium. This study suggests that individual patients felt the lung function benefits with IND/GLY compared with tiotropium, which, in turn, may also have contributed to the preference for IND/GLY.

Keywords: COPD; FEV1; dual bronchodilators; indacaterol/glycopyrronium; treatment choice; treatment preference.

Figure 1

Study design. Notes: During screening, patients received their current COPD treatment and were instructed to abstain from tiotropium inhalation on visit 3 (randomization). Inhaled corticosteroids were allowed to be taken throughout the study when started 30 days prior to screening visit. Abbreviations: IND/GLY, indacaterol/glycopyrronium; o.d., once daily; V, visit.

Figure 2

Patient disposition (full analysis set). Notes: ^aForty-three patients were randomized into the sequence 1 (IND/GLY – tiotropium) and 45 patients were randomized into sequence 2 (tiotropium – IND/GLY). Three patients randomized to the IND/GLY – tiotropium group were treated vice-versa (ie, tiotropium – IND/GLY). ^bOne patient discontinued due to adverse event in tiotropium – IND/GLY group after start of treatment period 2. Abbreviation: IND/GLY, indacaterol/glycopyrronium.

Figure 3

FEV₁ (L) 1 h post-inhalation after 4 weeks of each treatment (full analysis set). Note: Data are least square means ±95% CI. Abbreviations: FEV₁, forced expiratory volume in 1 s; IND/GLY, indacaterol/glycopyrronium.

Figure 4

Very important/important subjective reasons cited by patients and physicians for a preference for IND/GLY or tiotropium (full analysis set). Notes: Data are displayed as percentage of patients/physicians that rated the provided reasons from a 5-item scale (very important, important, neutral, unimportant, and very unimportant) as very important or important. Two patients and 1 physician did not answer the questionnaire. Abbreviation: IND/GLY, indacaterol/glycopyrronium.

Figure 5

Patients very satisfied/satisfied with their treatment (full analysis set). Notes: Data are displayed as percentage of patients that were very satisfied or satisfied with the medication in terms of the provided items. All patients answered the questionnaire with exception of 1 patient who discontinued the study. Abbreviation: IND/GLY, indacaterol/glycopyrronium.

Figure 6

TSQM-9 questionnaire results by domain (full analysis set). Notes: Data are least square mean (±95% CI) of TSQM-9 total scores by domain (effectiveness, convenience, and global satisfaction) determined after 4 weeks of treatment. *p=0.0001, **p=0.0035. All patients answered the questionnaire with exception of 1 patient who discontinued the study. Abbreviations: IND/GLY, indacaterol/glycopyrronium; TSQM-9, Treatment Satisfaction Questionnaire for Medication.

Figure 7

Improvement in FEV₁ (L) 1 h post-inhalation based on medication preference (full analysis set). Note: Data are in least square mean ±95% CI. Abbreviations: FEV₁, forced expiratory volume in 1 s; IND/GLY, indacaterol/glycopyrronium.