B Celli

Tiotropium HandiHaler® in the treatment of COPD: A safety review

Background Tiotropium is a long-acting inhaled anticholinergic developed for the treatment of chronic obstructive pulmonary disease (COPD) and has been available since 2002. We sought to update an evaluation of the safety of tiotropium in the HandiHaler® formulation as significant clinical trial data have become available over time. Methods Pooled analysis of adverse event reporting from phase III and IV tiotropium HandiHaler® clinical trials with the following characteristics was performed: randomized, double-blind, parallel group, placebo-controlled design, tiotropium 18 μg once-daily dosing, COPD indication, duration of at least four weeks. Incidence rates by treatment group, rate differences (tiotropium–placebo), and 95% confidence intervals were determined. Results Twenty-six trials were identified involving 17,014 patients. Mean age was 65 years, mean forced expiratory volume in one second was 1.16 L (41% predicted), 76% men. Total exposure to study drug was 11,958 patient-years (tiotropium) and 10,578 patient-years (placebo). Tiotropium was associated with a reduced risk (expressed as rate difference [95% confidence interval] per 100 patients-years at risk) for an adverse event (−17.5 [−22.9, −12.2]), serious adverse event (−1.41 [−2.81, −0.00]) and a fatal event (−0.63 [−1.14, −0.12]). A reduced risk was present for adverse events that were cardiac (−0.79 [−1.48, −0.09]), lower respiratory (−14.2 [−17.0, −11.5]) and for a composite endpoint of major adverse cardiovascular events (−0.45 [−0.85, −0.05]). Typical expected inhaled anticholinergic effects such as dry mouth, constipation, and urinary difficulties were observed in the safety database. Conclusion The safety data review does not indicate an increased risk for death or cardiovascular morbidity during tiotropium treatment in patients with COPD.

Longitudinal assessment in COPD patients: multidimensional variability and outcomes

The value and timing of multidimensional assessments in chronic obstructive pulmonary disease (COPD) remains unclear because there is little information about their variability and relationship to outcome. The aim of this study was to determine the progression of COPD using clinical and spirometric variability over time with mortality as the outcome. We determined the annual intra-individual variability of forced expiratory volume in 1 s (FEV1) and BODE (body mass index, airflow obstruction, dyspnoea, exercise capacity) index in 403 patients with at least five measurements. The pattern was defined as “stable” if the annual change remained constant in ≥66% of the observations and “unstable” if it did not meet that threshold. We explored the minimum number of yearly observations that related to mortality in the 704 patients of the cohort. The “unstable” pattern of FEV1 was seen in 53% and 40% of patients using a threshold of 40 mL·year−1 and 100 mL·year−1, respectively. There was a slightly more “stable” pattern in the BODE index (62% for 1 point). A profile associated with mortality was defined by a baseline measurement followed by annual measurements for 2 years of the BODE index, but not its individual components, including FEV1 (p<0.001). Progression of COPD measured using FEV1 is inconsistent and relates poorly to outcome. Monitoring the more stable BODE index better assesses disease progression. COPD patients have a high annual variability in FEV1. The BODE index is more stable and useful to assess COPD progression http://ow.ly/rO5T0

Clinical and prognostic heterogeneity of C and D GOLD groups

“High risk” groups for exacerbations of chronic obstructive pulmonary disease (COPD) in the 2011 Global Initiative for Chronic Obstructive Lung Disease (GOLD) proposal (i.e. groups C and D) [1] include: patients with a forced expiratory volume in 1 s FEV1 <50% reference and <2 exacerbations year-1 (subgroups C1 and D1); patients with ≥2 exacerbations·year-1 and an FEV1 ≥50% reference (subgroups C2 and D2); and patients with both FEV1 <50% ref. and ≥2 exacerbations·year-1 (subgroups C3 and D3) [2–5]. We hypothesised that these high-risk subgroups will differ in other clinical, functional and biological characteristics and will be associated with different long-term outcomes. We explored this hypothesis in the ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints) cohort [6, 7]. The results of this study show that “high-risk” COPD patients (GOLD groups C and D) are highly heterogeneous http://ow.ly/LTMOv