Tiotropium use in patients with COPD exacerbation improves airflow limitation and decreases health resource utilization

Tiotropium use in patients with chronic obstructive pulmonary disease (COPD) exacerbation led to decreased health resource utilization (HRU) and improved airflow limitation, according to a randomized, double-blind, multicenter, parallel group study published in the European Respiratory Journal.

Compared with placebo, COPD patients treated in France over 1 year with tiotropium 18 mcg once daily via the HandiHaler device improved COPD symptoms, used less "rescue" or other medication, and demonstrated less HRU than placebo-treated patients.

A total of 1,010 demographically similar patients aged ≥40 years were randomized and treated (n=510 for placebo and n=500 for tiotropium). Each patient performed a peak expiratory flow (PEF) test each morning before receiving medication and recorded the highest readings. Patients also recorded their "as-needed" medications and graded their respiratory condition from 0 (poor) to 10 (excellent). Spirometry was done at each clinic visit 30 minutes prior to dosing. Forced expiratory volume in 1 second (FEV₁), forced vital capacity (FVC), slow vital capacity (SVC), and inspiratory capacity (IC) all were measured. All tests were performed 3 times, and the highest readings were used. Adverse effects also were monitored. Except when patients discontinued because of worsening COPD, an intent-to-treat, last observation carried forward method was used. Statistical significance was set at P<.05.

Severe exacerbations were observed in 104 cases. Tiotropium reduced the proportion of patients having ≥1 moderate-to-severe COPD exacerbation, decreased the number of moderate-to-severe exacerbation days (all P<.0001), and reduced the overall number of exacerbations versus placebo. Active treatment also resulted in fewer hospitalizations and hospital days due to COPD events. Additionally, tiotropium-treated patients had significantly fewer unscheduled doctor visits and doctor calls (P<.05), and also used less additional respiratory medication (P<.0001). During exacerbations, tiotropium-treated patients used fewer and shorter courses of oral steroids (P<.01) and antibiotics (P<.001).

Weekly morning PEF values were significantly higher in tiotropium-treated patients from Week 1 through the study's conclusion (P<.0001 for all weekly intervals). At the end of treatment, tiotropium improved FEV₁ by 0.12±0.02 L (P<.0001), FVC by 0.17±0.03 L (P<.0001), SVC by 0.17±0.03 L (P<.0001), and IC by 0.14±0.04 L (P<.001). Fewer rescue medications were utilized by active treatment patients (P<.01 at all time points); these patients also had higher respiratory condition scores compared with placebo (P<.05 for 50 of 52 weeks).

In tiotropium-treated patients not treated with inhaled corticosteroids (ICS), statistical significance was not reached, nor was it reached for those patients with infrequent exacerbations.

To compare this study to others, a post-hoc analysis was performed, defining a severe exacerbation as one requiring hospitalization, a moderate exacerbation as one in which systemic steroids or antibiotics were needed, and all other exacerbations as mild. The analysis produced similar results (P<.001).

Tiotropium was well-tolerated and led to few study discontinuations with a decrease in HRU and improved airflow limitation. Adverse effects over the treatment period were similar in both groups, and discontinuation rates also were similar between the tiotropium and placebo groups (3% and 3.5%, respectively). Dry mouth was more common in the tiotropium-treated patients.

SOURCE Dusser D, Bravo M-L, Iacono P, on behalf of the MISTRAL study group. The effect of tiotropium on exacerbations and airflow in patients with COPD. Eur Respir J. 2006;27:547–555.