Effect of add-on therapy of tiotropium in COPD treated with theophylline

Abstract

Background: Although combination therapy with bronchodilators is recommended for chronic obstructive pulmonary disease (COPD), there is insufficient evidence for the efficacy of some combinations of long-acting bronchodilators.

Objective: We investigated the effects of a combination therapy with tiotropium and theophylline in COPD patients.

Methods: In a 12-week, open-labeled, parallel-group randomized study, pulmonary functions and dyspnea scores were compared between the combination and theophylline alone therapy at baseline, and 4 and 8 weeks after randomization in COPD.

Results: Sixty-one COPD patients completed the trial (31 combination therapy, 30 theophylline alone; mean age 70 years; 58 males; mean dyspnea score 2.0 and forced expiratory volume in one second (FEV1) 1.5 L [62.5% predicted]). FEV1 in the combination group, but not in the theophylline alone, was significantly increased at 4 (1.56 +/- 0.13 L, p < 0.001) and 8 weeks (1.60 +/- 0.13 L, p < 0.001) from the baseline (1.40 +/- 0.12 L). In the combination group, but not the theophylline alone group, the dyspnea score was significantly improved after 4 (p < 0.01) and 8 weeks (p <0.05) compared with baseline. In 17 patients who did not receive theophylline at screening, treatment with 4 or 8 weeks of theophylline alone did not improve dyspnea score or FEV1.

Conclusion: Addition of tiotropium therapy to theophylline treatment can improve dyspnea and pulmonary function in COPD. Although this study did not assess whether there was any benefit of adding theophylline to patients treated with tiotropium, tiotropium can be a useful addition in COPD already treated with theophylline.

Figure 1

Study design. Notes: ^†British Medical Research Council score. Combination therapy: theophylline with tiotropium.

Figure 2

Trial profile.

Figure 3

Changes in FVC and FEV₁ in the theophylline alone (white squares) and the combination therapy group (black squares). In a and b, absolute values of FVC and FEV₁ are shown. In c and d, percentage changes in FVC and FEV₁ from the baseline are shown. Notes: *p < 0.05, **p < 0.01, ***p < 0.001 compared with baseline values. ^†p < 0.05 between two groups. Abbreviations: FVC, forced vital capacity; FEV₁, forced expiratory volume in one second.

Figure 4

Changes in FVC and FEV₁ in the theophylline-alone (white squares, n = 17) and the combination therapy group (black squares, n = 25), in patients who did not receive regular treatment with theophylline at the time of screening. In a and b, absolute values of FVC and FEV₁ are shown. In c and d, percentage changes in FVC and FEV₁ from the baseline are shown. Notes: *p < 0.05, **p < 0.01, ***p < 0.001 compared with the baseline values. ^†p < 0.05 between two groups. Abbreviations: FVC, forced vital capacity; FEV₁, forced expiratory volume in one second.

Figure 5

Changes in VC, IC, PEFR, ⩒₅₀ and ⩒₂₅ at 8 weeks. Changes in VC, IC, PEFR, ⩒₅₀, and ⩒₂₅ at 8 weeks were analyzed in theophylline-alone (white bars, n = 26) and combination therapy (solid bars, n = 30) groups. Notes: *p < 0.05 compared with screening values. ^†p < 0.05 between two groups. Abbreviations: IC, inspiratory capacity; PEFR, peak expiratory flow rate; VC, vital capacity.

Figure 6

British Medical Research Council (MRC) scores 4 and 8 weeks after the addition of tiotropium. (a) MRC scores 4 and 8 weeks after the addition of tiotropium were analyzed in theophylline-alone (white bars, n = 29) and combination therapy (solid bars, n = 30) groups. (b) MRC scores 4 and 8 weeks after the addition of tiotropium were analyzed in 42 patients who were not receiving theophylline at the time of screening: theophylline-alone (white bars, n = 17) and combination therapy (solid bars, n = 25). Notes: *p < 0.05, p < 0.01 compared with baseline values.