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

Tomotaka Kawayama¹, Tomoaki Hoshino¹, Masao Ichiki², Toru Tsuda³, Masaharu Kinoshita⁴, Shohei Takata⁵, Takeharu Koga¹, Tomoaki Iwanaga¹, Hisamichi Aizawa¹, Kurume COPD Study Group*

¹Department of Medicine, Kurume University School of Medicine, Kurume, Japan; ²Division of Respiratory Medicine, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan; ³Tsuda Hospital, Kitakyushu, Japan; ⁴Nagata Hospital, Yanagawa, Japan; ⁵National Hospital Organization Fukuoka-Higashi Medical Center, Fukuoka, Japan

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.

Keywords: chronic obstructive pulmonary disease, long acting anticholinergics agent, tiotropium, slow release theophylline, combination therapy