Clinical Efficacy and Safety of Transdermal Tulobuterol in the Treatment of Stable COPD: An Open-Label Comparison with Inhaled Salmeterol
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Background: Long-acting bronchodilators are recommended for the management of stable COPD to relieve symptoms and improve quality of life. The tulobuterol patch (Hokunalin®) is a transdermal patch preparation of the β2-adrenoceptor agonist (β2-agonist) tulobuterol designed to yield sustained β2-agonistic effects for 24 hours when applied once daily.
Objective: To compare the effectiveness of tulobuterol patch and inhaled salmeterol (Serevent® Diskus) in the treatment of stable COPD.
Study design: Clinically stable COPD patients (age ≥40 years, postbronchodilator FEV1/FVC <70%, and postbronchodilator FEV1 <80% predicted) were enrolled in a multicenter, open-label randomized study. After a 2-week run-in period, patients were administered either tulobuterol (2mg once-daily applied as a patch) or salmeterol (50μg per inhalation, twice a day) for 12 weeks.
Results: Data for 92 patients (46 each for each treatment group) were analyzed. There were no significant differences in baseline characteristics in the tulobuterol versus salmeterol groups: age, 69.2 ± 7.4 vs 71.6 ± 7.3 years; male, 91% versus 96%; and patients with stage II (III) COPD, 32.6% (67.4%) versus 50% (50%). FEV1, FVC, and PEF improved during treatment in both groups compared with baseline, with no significant between group differences. The total St George’s Respiratory Questionnaire (SGRQ) score was significantly improved relative to baseline in the tulobuterol group at 8 weeks (−4.7 units [U]), but not in the salmeterol group at all timepoints. Domain analysis of the SGRQ scores revealed significant improvement in the symptom score relative to baseline in the tulobuterol group at weeks 4 (−6.9U), 8 (−12.0U), and 12 (−11.7U), but not in the salmeterol group in any of the domains tested. Medical Research Council dyspnea scale score improved during treatment in both groups, with no significant differences between groups. Compliance with the treatment regimen was significantly better in the tulobuterol than in the salmeterol group (98.5% vs 94.1%; p < 0.05).
Conclusion: These findings indicate that once-daily transdermal sustained-release tulobuterol is as effective or better than the inhaled long-acting β2-agonist salmeterol in the management of stable COPD, with significant effects on quality of life.
The BAREC Research Group consists of the following investigators: Yoshinosuke Fukuchi, Department of Respiratory Medicine, Juntendo University School of Medicine; Atsushi Nagai, Tokyo Women’s Medical University Respiratory Center; Masaharu Nishimura, First Department of Internal Medicine, Hokkaido University; Hiromasa Ogawa, Department of Internal Medicine, Tohoku University Graduate School of Medicine; Keishi Kubo, First Department of Internal Medicine, Shinshu University School of Medicine; Yukihiko Sugiyama, Division of Pulmonary Medicine, Department of Medicine, Jichi Medical School; Takayuki Kuriyama, Department of Respirology, Chiba University School of Medicine; Kazuhiro Yamaguchi, Department of Medicine, Keio University School of Medicine; Ken Matsuoka, Kasumigaura Hospital, Tokyo Medical University; Ken Ohta, Department of Internal Medicine, Teikyo University School of Medicine; Shoji Kudoh, Fourth Department of Internal Medicine, Nippon Medical School; Shu Hashimoto, First Department of Internal Medicine, Nihon University School of Medicine; Kuniaki Seyama, Department of Respiratory Medicine, Juntendo University School of Medicine; Keiji Takahashi, Department of Respiratory Medicine, Kanazawa Medical University; Hirohisa Toga, Department of Respiratory Medicine, Kanazawa Medical University; Michiaki Mishima, Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University; Masakazu Ichinose, Third Department of Internal Medicine, Wakayama Medical University; Kazuto Hirata, Division of Respiratory Medicine, Osaka City University; and Hisamichi Aizawa, First Department of Internal Medicine, Kurume University School of Medicine.
No sources of funding were used to assist in the preparation of this manuscript. The authors have no potential conflicts of interest that are directly relevant to the contents of this manuscript.
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