Christian Bartels(1), Peter D'Andrea(2), Donald Banerji(2), Robert Fogel(2), Francesco Patalano(1), David Morris(1), Jessica Marvel(2)
(1)Novartis Pharma AG, Basel, Switzerland; (2)Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA
Objectives: The measurement of lung function by spirometry (specifically FEV1) is routinely used to measure the efficacy of bronchodilators. However, measurement of patient’s outcomes is also important as it directly reflects the patient’s quality of life. Previous studies have shown FEV1 can be a good predictor of future morbidity, and mortality, patient reported outcomes (PROs) and exacerbation frequency [1][2]; however, they did not include information on COPD patients treated with a LABA/LAMA combination.
This patient level pooled analysis of COPD clinical trials further characterizes the correlation between FEV1, and patient outcomes as measured by St Georges Respiratory Questionnaire (SGRQ) in COPD patients treated with LABA (indacaterol), LAMA (glycopyrronium) and LABA/LAMA dual bronchodilator, QVA149 (fixed-dose combination of indacaterol maleate and glycopyrronium bromide).
Methods: Pooled data from twenty-three randomized, parallel-group, placebo- or active-controlled studies (3 to 18 months duration; 23,213 patients) on FEV1 and SGRQ scores in COPD patients was analyzed using descriptive statistics of correlations. Linear mixed effect models were used to determine, if changes in FEV1 can predict improvements in patient outcomes.
Results: Summary statistics showed statistically significant correlations between FEV1 and SGRQ. Compared to patients with a small response in FEV1, patients with larger response in FEV1 had on average better SGRQ scores.
Longitudinal mixed effects models demonstrated that the change in FEV1 from baseline was predictive of change in SGRQ. The models attributed part of the treatment efficacy in SGRQ to improvements in FEV1.
Analyses of simulated data generated assuming a strong association of SGRQ and FEV1 and taking into account variability of the FEV1 measurements illustrated that due to regression dilution bias[3] the mixed effects models underestimate correlations.
Conclusions: The analysis showed that there is a statistically significant correlation between the average change in FEV1 from baseline and change in SGRQ from baseline. FEV1 change from baseline has been shown to be a predictive marker in assessing the effectiveness of bronchodilation treatment in COPD patients. Due to variability of FEV1 measurements, correlations with other endpoints are underestimated. Efficacy in SGRQ may be primarily due to bronchodilation which is measured by FEV1.
References:
[1] Young et al., Eur. Respir. J. 2007;30: 616-22
[2] Westwood et al., Respir. Res. 2011;12:40
[3] Frost et al., J. R. Statist. Soc. A 2000 ;163:173-89
Reference: PAGE 24 (2015) Abstr 3400 [www.page-meeting.org/?abstract=3400]
Poster: Drug/Disease modeling - Other topics