The efficacy and safety of combined tiotropium and olodaterol via the Respimat(®) inhaler in patients with COPD: results from the Japanese sub-population of the Tonado(®) studies.
BACKGROUND
The efficacy and safety of once-daily tiotropium + olodaterol (T+O) maintenance treatment was demonstrated in the large, multinational, replicate, randomized, Phase III, Tonado(®) 1 (NCT01431274) and 2 (NCT01431287) studies in patients with moderate to very severe COPD. However, there may be racial differences in the effects of T+O on lung function in patients with COPD.


METHODS
In this Tonado(®) subgroup analysis, we assessed efficacy and safety of T+O in Japanese participants.


RESULTS
Versus the overall population, the 413 Japanese patients randomized and treated were slightly older, with more men, lower body mass index, lower baseline St George's Respiratory Questionnaire (SGRQ) scores, fewer current smokers, but with higher pack-year smoking history. A lower proportion of Japanese patients used inhaled corticosteroids, short-acting muscarinic antagonists, or short- or long-acting β-adrenergic agonists at baseline, but use of long-acting muscarinic antagonists was higher. At Week 24, mean improvements with T+O 5/5 μg in forced expiratory volume in 1 second area under the curve from 0-3 hours response were 151 mL versus olodaterol and 134 mL versus tiotropium 5 μg; mean improvements with T+O 2.5/5 μg were 87 mL versus olodaterol and 70 mL versus tiotropium 2.5 μg. Mean improvements with T+O 5/5 μg in trough forced expiratory volume in 1 second were 131 mL versus olodaterol and 108 mL versus tiotropium 5 μg; mean improvements with T+O 2.5/5 μg were 60 mL versus olodaterol and 47 mL versus tiotropium 2.5 μg. SGRQ scores improved from baseline to a greater extent with both doses of T+O versus monotherapies. Responses were similar in the overall population. Adverse-event incidence was generally balanced across treatment groups.


CONCLUSIONS
Consistent with results from the overall population, T+O 5/5 μg was superior to each monotherapy for lung function and SGRQ in the Japanese sub-population of patients with COPD in Tonado(®).
Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
Masakazu
M
Ichinose
Department of Respiratory Medicine and Allergy, Tosei General Hospital, Aichi, Japan.
Hiroyuki
H
Taniguchi
Nippon Boehringer Ingelheim Co. Ltd, Tokyo, Japan.
Ayako
A
Takizawa
Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany.
Lars
L
Grönke
Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany.
Lazaro
L
Loaiza
Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany.
Florian
F
Voß
Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut, USA.
Yihua
Y
Zhao
Juntendo University School of Medicine, Tokyo, Japan.
Yoshinosuke
Y
Fukuchi
D000280:Administration, Inhalation; D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage* / Q000009:adverse effects; D000368:Aged; D048588:Benzoxazines / Q000008:administration & dosage* / Q000009:adverse effects; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000009:adverse effects; D018680:Cholinergic Antagonists / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004338:Drug Combinations; D004867:Equipment Design; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D007564:Japan; D008168:Lung / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009330:Nebulizers and Vaporizers; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D020127:Recovery of Function; D012720:Severity of Illness Index; D013997:Time Factors; D000069447:Tiotropium Bromide / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome
D058666:Adrenergic beta-2 Receptor Agonists; D048588:Benzoxazines; D001993:Bronchodilator Agents; D018680:Cholinergic Antagonists; D004338:Drug Combinations; C000611386:tiotropium-olodaterol; D000069447:Tiotropium Bromide
COPD; bronchodilators; maintenance treatment