{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T13:57:42Z","timestamp":1760623062981,"version":"3.37.3"},"reference-count":14,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,10,23]],"date-time":"2017-10-23T00:00:00Z","timestamp":1508716800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,10,23]],"date-time":"2017-10-23T00:00:00Z","timestamp":1508716800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["npj Prim Care Resp Med"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>This analysis provides a comprehensive clinical assessment of the long-term safety of the licensed dose of olodaterol (5\u2009\u00b5g once daily [QD] via Respimat<jats:sup>\u00ae<\/jats:sup> inhaler) in patients with chronic obstructive pulmonary disease by exploring the occurrence of acknowledged side effects of long-acting \u03b2<jats:sub>2<\/jats:sub>-agonists as well as those included in the olodaterol and formoterol labels. We analysed pooled data from two replicate, double-blind studies of olodaterol (5\u2009\u00b5g QD via Respimat<jats:sup>\u00ae<\/jats:sup>) compared to formoterol (12\u2009\u00b5g twice daily [BID]) or placebo over 48 weeks (1222.13, NCT00793624; 1222.14, NCT00796653). Patients could continue their background treatment. The analysis considered adverse events (AEs) typically associated with \u03b2<jats:sub>2<\/jats:sub>-agonists, including cardiovascular events, as well as administration-related events. Descriptive statistics were provided for the incidence of AEs and aggregated AEs. The analysis included 1379 patients: 460 placebo, 459 olodaterol and 460 formoterol; AEs were reported by 70.9, 71.7 and 69.1% of patients, respectively. Exposure-adjusted incidence rates of cardiac AEs (arrhythmia and myocardial ischaemia) and cough were numerically lower in the olodaterol group than the formoterol group, while nasopharyngitis, throat irritation, metabolism and psychiatric disorders were numerically higher in the olodaterol group. The most frequent event in the olodaterol group was nasopharyngitis (placebo 8.0%; olodaterol 12.9%; formoterol 10.0%). Except for cough (incidence rate ratio of 0.46 [95% confidence interval 0.24, 0.89] in favour of olodaterol), there were no significant differences between active groups. In conclusion, olodaterol 5\u2009\u00b5g QD was well tolerated over 48 weeks with a typical \u03b2<jats:sub>2<\/jats:sub>-agonist safety profile comparable to formoterol 12\u2009\u00b5g BID.<\/jats:p>","DOI":"10.1038\/s41533-017-0059-1","type":"journal-article","created":{"date-parts":[[2017,10,10]],"date-time":"2017-10-10T14:11:09Z","timestamp":1507644669000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Comprehensive assessment of the safety of olodaterol 5\u2009\u00b5g in the Respimat\u00ae device for maintenance treatment of COPD: comparison with the long-acting \u03b22-agonist formoterol"],"prefix":"10.1038","volume":"27","author":[{"given":"Andrea","family":"Koch","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henrik","family":"Watz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. Reza","family":"Maleki-Yazdi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6515-0841","authenticated-orcid":false,"given":"Ulrich","family":"Bothner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kay","family":"Tetzlaff","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Florian","family":"Vo\u00df","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lorcan","family":"McGarvey","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2017,10,23]]},"reference":[{"key":"59_CR1","unstructured":"Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease, updated 2016. http:\/\/www.goldcopd.org\/ (2016)."},{"key":"59_CR2","doi-asserted-by":"publisher","DOI":"10.1186\/1465-9921-11-149","volume":"11","author":"DP Tashkin","year":"2010","unstructured":"Tashkin, D. P. & Fabbri, L. M. Long-acting beta-agonists in the management of chronic obstructive pulmonary disease: current and future agents. Respir. Res. \n                           11, 149 (2010).","journal-title":"Respir. Res."},{"key":"59_CR3","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1016\/j.pupt.2008.11.010","volume":"22","author":"C Cote","year":"2009","unstructured":"Cote, C., Pearle, J. L., Sharafkhaneh, A. & Spangenthal, S. Faster onset of action of formoterol versus salmeterol in patients with chronic obstructive pulmonary disease: a multicenter, randomized study. Pulm. Pharmacol. Ther. \n                           22, 44\u201349 (2009).","journal-title":"Pulm. Pharmacol. Ther."},{"key":"59_CR4","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1038\/bjp.2008.284","volume":"155","author":"M Cazzola","year":"2008","unstructured":"Cazzola, M. & Matera, M. G. Novel long-acting bronchodilators for COPD and asthma. Br. J. Pharmacol. \n                           155, 291\u2013299 (2008).","journal-title":"Br. J. Pharmacol."},{"key":"59_CR5","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1016\/j.rmed.2010.11.027","volume":"105","author":"H Worth","year":"2011","unstructured":"Worth, H., Chung, K. F., Felser, J. M., Hu, H. & Rueegg, P. Cardio- and cerebrovascular safety of indacaterol vs formoterol, salmeterol, tiotropium and placebo in COPD. Respir. Med. \n                           105, 571\u2013579 (2011).","journal-title":"Respir. Med."},{"key":"59_CR6","doi-asserted-by":"publisher","first-page":"53","DOI":"10.2147\/COPD.S39018","volume":"8","author":"ML Decramer","year":"2013","unstructured":"Decramer, M. L., Hanania, N. A., L\u00f6tvall, J. O. & Yawn, B. P. The safety of long-acting \u03b22-agonists in the treatment of stable chronic obstructive pulmonary disease. Int. J. Chron. Obstruct. Pulmon. Dis. \n                           8, 53\u201364 (2013).","journal-title":"Int. J. Chron. Obstruct. Pulmon. Dis."},{"key":"59_CR7","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1378\/chest.114.2.411","volume":"114","author":"M Cazzola","year":"1998","unstructured":"Cazzola, M. et al. Cardiac effects of formoterol and salmeterol in patients suffering from COPD with preexisting cardiac arrhythmias and hypoxemia. Chest \n                           114, 411\u2013415 (1998).","journal-title":"Chest"},{"key":"59_CR8","unstructured":"Boehringer Ingelheim International GmbH. Striverdi Respimat 2.5 microgram, solution for inhalation SPC. http:\/\/www.medicines.org.uk\/emc\/medicine\/28992 (2016)."},{"key":"59_CR9","doi-asserted-by":"publisher","first-page":"484","DOI":"10.3109\/15412555.2014.991864","volume":"12","author":"L McGarvey","year":"2015","unstructured":"McGarvey, L. et al. One-year safety of olodaterol once daily via Respimat\u00ae in patients with GOLD 2\u20134 chronic obstructive pulmonary disease: results of a pre-specified pooled analysis. COPD \n                           12, 484\u2013493 (2015).","journal-title":"COPD"},{"key":"59_CR10","doi-asserted-by":"publisher","first-page":"477","DOI":"10.2147\/COPD.S23816","volume":"6","author":"JF Donohue","year":"2011","unstructured":"Donohue, J. F. et al. Safety of indacaterol in the treatment of patients with COPD. Int. J. Chron. Obstruct. Pulmon. Dis. \n                           6, 477\u2013492 (2011).","journal-title":"Int. J. Chron. Obstruct. Pulmon. Dis."},{"key":"59_CR11","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1378\/chest.11-2231","volume":"142","author":"NA Hanania","year":"2012","unstructured":"Hanania, N. A. et al. The efficacy and safety of the novel long-acting \u03b22 agonist vilanterol in patients with COPD: a randomized placebo-controlled trial. Chest \n                           142, 119\u2013127 (2012).","journal-title":"Chest"},{"key":"59_CR12","doi-asserted-by":"publisher","DOI":"10.1186\/s40248-015-0023-2","volume":"10","author":"RW Dal Negro","year":"2015","unstructured":"Dal Negro, R. W., Bonadiman, L. & Turco, P. Prevalence of different comorbidities in COPD patients by gender and GOLD stage. Multidiscip. Respir. Med. \n                           10, 24 (2015).","journal-title":"Multidiscip. Respir. Med."},{"key":"59_CR13","unstructured":"Novartis Pharmaceuticals UK Ltd. Foradil\u00ae. 12 micrograms inhalation powder, hard capsule SPC. http:\/\/www.medicines.org.uk\/emc\/medicine\/1286 (2016)."},{"key":"59_CR14","doi-asserted-by":"publisher","first-page":"697","DOI":"10.2147\/COPD.S62502","volume":"9","author":"A Koch","year":"2014","unstructured":"Koch, A. et al. Lung function efficacy and symptomatic benefit of olodaterol once daily delivered via Respimat\u00ae versus placebo and formoterol twice daily in patients with GOLD 2\u20134 COPD: results from two replicate 48-week studies. Int. J. Chron. Obstruct. Pulmon. Dis. \n                           9, 697\u2013714 (2014).","journal-title":"Int. J. Chron. Obstruct. Pulmon. Dis."}],"container-title":["npj Primary Care Respiratory Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41533-017-0059-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41533-017-0059-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41533-017-0059-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,23]],"date-time":"2022-12-23T01:40:20Z","timestamp":1671759620000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41533-017-0059-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,10,23]]},"references-count":14,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2017,12]]}},"alternative-id":["59"],"URL":"https:\/\/doi.org\/10.1038\/s41533-017-0059-1","relation":{},"ISSN":["2055-1010"],"issn-type":[{"type":"electronic","value":"2055-1010"}],"subject":[],"published":{"date-parts":[[2017,10,23]]},"assertion":[{"value":"7 February 2017","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 August 2017","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 September 2017","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 October 2017","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"A.K. has received a grant from Actelion Pharmaceuticals and has taken part in congresses for Boehringer Ingelheim, Almirall, Bayer, TEVA, Roche, Actelion and Novartis. H.W. reports personal fees for consulting and compensation for his institution during the conduct of the study from Boehringer Ingelheim related to the submitted work, and participation in advisory boards for Almirall, AstraZeneca, Boehringer Ingelheim and GlaxoSmithKline, in lectures for Almirall, AstraZeneca, Boehringer Ingelheim, BerlinChemie, GlaxoSmithKline, Novartis and Chiesi, and congress travel support from GlaxoSmithKline and Novartis outside the submitted work; his institution has also received compensation for the conduct of clinical studies from Almirall, AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Novartis, Chiesi, Takeda, AB2BIO, Bayer and Intermune outside the submitted work. M.R.M.-Y. declares that he has no competing financial interests. U.B., K.T. and F.V. are employees of Boehringer Ingelheim. L.M. reports personal fees from Applied Clinical Intelligence during the conduct of the study, grants from Asthma UK, NI Chest Heart & Stroke, NC3Rs, British Heart Foundation and Chiesi, travel and subsistence for attendance at scientific meetings from Boehringer Ingelheim, GlaxoSmithKline and Chiesi, and advisory board\/consultancy fees from Almirall, NAPP, GlaxoSmithKline and Boehringer Ingelheim outside the submitted work.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"60"}}