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We evaluated the efficacy and safety of rabeprazole maintenance therapy at 10\u00a0mg once daily (q.d.) or b.i.d. for longer than 8\u00a0weeks.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Patients with RE refractory to standard PPI regimens for at least 8\u00a0weeks were enrolled. They were treated with rabeprazole at 10 or 20\u00a0mg b.i.d. for 8\u00a0weeks during the open-label treatment period. After endoscopic examination, those with confirmed healing entered the subsequent double-blind maintenance therapy. During this period, the subjects were randomized to receive rabeprazole 10\u00a0mg q.d. (control) or 10\u00a0mg b.i.d. The primary endpoint was the endoscopic no-recurrence rate at Week 52.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In total, 517 subjects entered the treatment, and 359 subjects continued on maintenance therapy. The full analysis set for central assessment included 343 subjects. The no-recurrence rate at Week 52 was significantly higher in the b.i.d. group (73.9%;<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.001, \u03c7<jats:sup>2<\/jats:sup>test) than in the q.d. group (44.8%). In particular, the b.i.d. regimen was more effective in all subgroups with Los Angeles Classification Grade B to D at treatment entry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In the maintenance treatment of PPI-resistant RE, rabeprazole at 10\u00a0mg b.i.d. exerted a stronger recurrence-preventing effect than 10\u00a0mg q.d. over 52\u00a0weeks. No particular safety issues were noted during long-term administration.<\/jats:p><jats:p><jats:italic>ClinicalTrials.gov number<\/jats:italic>: NCT02135107.<\/jats:p><\/jats:sec>","DOI":"10.1007\/s00535-017-1417-z","type":"journal-article","created":{"date-parts":[[2017,11,29]],"date-time":"2017-11-29T10:09:58Z","timestamp":1511950198000},"page":"834-844","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Efficacy and safety of twice-daily rabeprazole maintenance therapy for patients with reflux esophagitis refractory to standard once-daily proton pump inhibitor: the Japan-based EXTEND study"],"prefix":"10.1007","volume":"53","clinical-trial-number":[{"clinical-trial-number":"nct02135107","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Yoshikazu","family":"Kinoshita","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mototsugu","family":"Kato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsuhiro","family":"Fujishiro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hironori","family":"Masuyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryo","family":"Nakata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hisanori","family":"Abe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinji","family":"Kumagai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasushi","family":"Fukushima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiumi","family":"Okubo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seiichiro","family":"Hojo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Motoyasu","family":"Kusano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,11,29]]},"reference":[{"key":"1417_CR1","doi-asserted-by":"publisher","first-page":"1069","DOI":"10.1111\/j.1365-2036.2007.03454.x","volume":"26","author":"F Moki","year":"2007","unstructured":"Moki F, Kusano M, Mizuide M, et al. 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Mototsugu Kato received honoraria from AstraZeneca K.K., Eisai Co., Ltd., Daiichi Sankyo Co., Ltd., Takeda Pharmaceutical Co., Ltd. and Otsuka Pharmaceutical Co., Ltd., and research grants from Abbott Japan Co., Ltd., Eisai Co., Ltd., Daiichi Sankyo Co., Ltd. and Astellas Pharma Co., Ltd. Mitsuhiro Fujishiro received honoraria from HOYA Co., Ltd., Takeda Pharmaceutical Co., Ltd., AstraZeneka K.K., Zeria Pharmaceutical Co., Ltd. and Daiichi Sankyo Co., Ltd., and received research grants from Takeda Pharmaceutical Co., Ltd. and EA Pharma Co., Ltd. Hironori Masuyama received research grants from Eisai Co., Ltd. and Takeda Pharmaceutical Co., Ltd. Yoshiumi Okubo is an employee of EA Pharma Co., Ltd. Seiichiro Hojo is an employee of Eisai Co., Ltd. Motoyasu Kusano received honoraria and research grants from Eisai Co., Ltd., EA Pharma Co., Ltd., Daiichi Sankyo Co., Ltd., Takeda Pharmaceutical Co., Ltd., AstraZeneca K.K., Otsuka Pharmaceutical Co., Ltd., TSUMURA & CO., Zeria Pharmaceutical Co., Ltd. and Astellas Pharma Co., Ltd. The following authors declare that they have no conflict of interest: Ryo Nakata, Hisanori Abe, Shinji Kumagai, and Yasushi Fukushima.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"This study was funded by Eisai, Co., Ltd., Tokyo, Japan and EA Pharma Co., Ltd., Tokyo, Japan. The writing and preparation of this paper were funded in part by EA Pharma. Writing support was provided by Eisai. Data analyses were undertaken by Eisai.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Funding"}}]}}