Efficacy of Tiotropium in COPD Patients with FEV1 ≥ 60% Participating in the UPLIFT® Trial

Abstract

GOLD stage II COPD encompasses patients with FEV₁ 50-80% predicted. A published trials review suggested that benefits of maintenance therapy are limited to patients with FEV₁ <60% predicted. We previously reported data demonstrating the efficacy of tiotropium in GOLD stage II disease in the 4-year UPLIFT® trial, and present here a further analysis of a sub-category of GOLD stage II patients with post-bronchodilator FEV1 ≥60% predicted from UPLIFT®. Outcomes included pre- and post-bronchodilator spirometry, exacerbations, SGRQ and mortality. Of the 5,992 UPLIFT® cohort, 1,210 (632 tiotropium, 578 control) had baseline post-bronchodilator FEV₁ ≥60% predicted (range 60-78%), mean age was 64 years, 70% were men, and mean SGRQ total score was 39.9 units. Mean annual rate of post-bronchodilator FEV₁ decline was 41 (tiotropium) and 49 (control) mL/year (P = 0.07); corresponding pre-bronchodilator values were 32 and 37 mL/year (P = 0.24). Morning pre-drug FEV₁ and FVC improvements for tiotropium versus control were 87-127 mL and 139-186 ml, respectively (P < 0.001, all time-points). SGRQ total score improvements (tiotropium-control) were 2.0-3.4 units (P < 0.05 for all); a higher percentage of patients had an improvement of ≥4 units with tiotropium (P <0.05). Tiotropium reduced risk for an exacerbation (HR [95% CI] = 0.83 [0.71, 0.96]) and mortality for the 4-year protocol-defined treatment period (HR [95% CI] = 0.66 [0.45, 0.96]). Tiotropium treatment provides clinical efficacy in patients with GOLD stage II disease with an FEV₁ ≥60% predicted, supporting current GOLD guidelines for COPD treatment. (ClinicalTrials.gov number NCT00144339).

Acute Exacerbations and Lung Function Loss in Smokers with and without Chronic Obstructive Pulmonary Disease

“…First is the possibility that preventing exacerbations in this subpopulation could reduce the risk of developing severe COPD, an important hypothesis that should motivate randomized trials. The possibility that mildto-moderate disease may be more amenable to therapy than severe airflow obstruction is supported by the UPLIFT study, which suggested that exacerbations, mortality, and perhaps FEV 1 decline were all reduced by tiotropium in subjects with FEV 1 greater than 60% (28). The link between exacerbations and lung function decline has been questioned, in part because many drugs reduce the risk of exacerbation but none have been definitively shown to reduce FEV 1 loss.…”

Functional Capacity, Health Status, and Inflammatory Biomarker Profile in a Cohort of Patients With Chronic Obstructive Pulmonary Disease

“…6MWD has been shown to correlate with both disease specific and generic HRQL instruments, such as the St. George’s Respiratory Questionnaire (SGRQ) 14 and the Medical Outcomes SF-36 questionnaire (SF-36), 15 respectively. Although the disease specific SGRQ has been validated in large therapeutic trials, such as TORCH and UPLIFT, 16 and in observational studies such as ECLIPSE, 2 relatively few studies have examined the relationship of the 6MWD with generic measures of quality of life such as the SF-36, which measures overall health status including effects of co-morbid diseases. Of importance, no study has evaluated the relationship between HRQL domains of the SGRQ and SF-36 and patients’ ability to walk more or less than the 350m, 17 despite the considerable prognostic value of this functional threshold.…”

Efficacy and safety of QVA149 compared to the concurrent administration of its monocomponents indacaterol and glycopyrronium: the BEACON study

“…Also, peak FEV 1 values revealed that the maximum improvements seen with the lung function were similar in both treatment groups. The symptomatic improvements achieved by patients in the QVA149 treatment group reinforced the association between improvements in lung function with other clinical outcomes 5,26…”