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An extended time-to-escalation to triple therapy suggests patients are in a stable condition and is an indicator of treatment effectiveness. No studies in Japanese clinical practice have compared the effectiveness of LAMA\/LABA fixed-dose combination therapies with LAMA monotherapy in terms of time-to-escalation to triple therapy. The primary objective of this real-world study in Japan was to compare time-to-escalation to triple therapy among new users of tiotropium\/olodaterol or tiotropium monotherapy for COPD without asthma.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>In this active-comparator cohort study, new users of tiotropium\/olodaterol (n\u2009=\u20091436) and tiotropium monotherapy (n\u2009=\u20095352) were identified from a large Japanese hospital-based database (Medical Data Vision Co., Ltd., Tokyo; prespecified study period: 1 April 2015 to 31 March 2019); patients in each group were matched 1:1 using high-dimensional propensity scores (hdPS). The primary outcome was time-to-escalation to triple therapy.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>For the prespecified study period in the hdPS-matched cohort, escalation to triple therapy was infrequent among new users of tiotropium\/olodaterol (n\u2009=\u20091302, 7 escalation events) and tiotropium monotherapy (n\u2009=\u20091302, 8 escalation events). The difference in time-to-escalation to triple therapy between groups was not statistically significant (median [interquartile range]: 28\u00a0days [15.0\u2013139.2] for tiotropium monotherapy vs 193\u00a0days [94.5\u2013302.0] for tiotropium\/olodaterol; hazard ratio: 0.89; 95% CI: 0.32\u20132.46). Similar findings (hazard ratio: 0.71; 95% Cl: 0.36\u20131.40) were observed in a post hoc analysis, which extended the study period by 1\u00a0year to 31 March 2020. Risks of first moderate and\/or severe COPD exacerbation were lower for tiotropium\/olodaterol than tiotropium monotherapy (between-group differences not significant). There were no significant between-group differences for the risks of all-cause inpatient mortality, major adverse cardiovascular events, and first use of home oxygen therapy.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>ICS monotherapy or ICS\/LABA added to tiotropium or tiotropium\/olodaterol is limited in Japanese clinical settings. The number of escalations to triple therapy was very limited in the dataset and there was insufficient power to detect differences between the treatment groups in the primary hdPS-matched cohort.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12931-021-01776-y","type":"journal-article","created":{"date-parts":[[2021,6,17]],"date-time":"2021-06-17T19:03:05Z","timestamp":1623956585000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Real-world effectiveness of early intervention with fixed-dose tiotropium\/olodaterol vs tiotropium in Japanese patients with COPD: a high-dimensional propensity score\u2013matched cohort analysis"],"prefix":"10.1186","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7452-9191","authenticated-orcid":false,"given":"Shigeo","family":"Muro","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masaru","family":"Suzuki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuhei","family":"Nakamura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jocelyn Ruoyi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth M.","family":"Garry","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wataru","family":"Sakamoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sabrina","family":"de Souza","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,6,17]]},"reference":[{"issue":"6","key":"1776_CR1","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1016\/S2213-2600(20)30105-3","volume":"8","author":"GBD Chronic Respiratory Disease Collaborators","year":"2020","unstructured":"GBD Chronic Respiratory Disease Collaborators. 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Accessed 3 Nov 2020."}],"container-title":["Respiratory Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12931-021-01776-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12931-021-01776-y\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12931-021-01776-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,6,17]],"date-time":"2021-06-17T19:04:04Z","timestamp":1623956644000},"score":1,"resource":{"primary":{"URL":"https:\/\/respiratory-research.biomedcentral.com\/articles\/10.1186\/s12931-021-01776-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,17]]},"references-count":49,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["1776"],"URL":"https:\/\/doi.org\/10.1186\/s12931-021-01776-y","relation":{},"ISSN":["1465-993X"],"issn-type":[{"type":"electronic","value":"1465-993X"}],"subject":[],"published":{"date-parts":[[2021,6,17]]},"assertion":[{"value":"28 January 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 June 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 June 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The study was conducted in accordance with the Japanese Ethical Guidelines for Medical and Health Research Involving Human Subjects and a protocol that was approved by an Independent Ethics Committee (Japan Conference of Clinical Research). Patient informed consent was not required because the study used retrospective de-identified data.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"SM has received lecture fees from Nippon Boehringer Ingelheim Co., Ltd., AstraZeneca, GlaxoSmithKline, and Novartis. MS has received research funding from Nippon Boehringer Ingelheim Co., Ltd. and Novartis, and lecture fees from Nippon Boehringer Ingelheim Co., Ltd., AstraZeneca, GlaxoSmithKline, and Novartis. JRW was an employee and with stock options at Aetion Inc. at the time the study was conducted and now has equity. EMG is an employee and holds stock options at Aetion Inc. Aetion was funded by Nippon Boehringer Ingelheim Co., Ltd. to collect the data and conduct the analyses. SN and WS are employees of Nippon Boehringer Ingelheim Co., Ltd. SdS is an employee of Boehringer Ingelheim International GmbH.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"180"}}