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Original article
Vonoprazan prevents ulcer recurrence during long-term NSAID therapy: randomised, lansoprazole-controlled non-inferiority and single-blind extension study
  1. Yuji Mizokami1,
  2. Kazunori Oda2,
  3. Nobuo Funao2,
  4. Akira Nishimura2,
  5. Satoshi Soen3,
  6. Takashi Kawai4,
  7. Kiyoshi Ashida5,
  8. Kentaro Sugano6
  1. 1 Endoscopic Center, University of Tsukuba Hospital, Tsukuba, Japan
  2. 2 Takeda Development Center, Takeda Pharmaceutical Company Ltd, Osaka, Japan
  3. 3 Department of Orthopaedic Surgery and Rheumatology, Kindai University Nara Hospital, Ikoma, Japan
  4. 4 Endoscopy Center, Tokyo Medical University Hospital, Tokyo, Japan
  5. 5 Department of Gastroenterology, Rakuwakai Otowa Hospital, Kyoto, Japan
  6. 6 Department of Medicine, Jichi Medical University, Tochigi, Japan
  1. Correspondence to Professor Yuji Mizokami, Endoscopic Center, University of Tsukuba Hospital, Tsukuba, Ibaraki 305-8576, Japan; yuji-mizokami{at}md.tsukuba.ac.jp

Abstract

Objective To assess the non-inferiority of vonoprazan to lansoprazole for secondary prevention of non-steroidal anti-inflammatory drug (NSAID)-induced peptic ulcer (PU) and the safety of vonoprazan during extended use.

Design A phase 3, 24-week, multicenter, randomised, double-blind (DB), active-controlled study, followed by a phase 3, ≥28 week, multicenter, single-blind, parallel-group extension study (EXT) in outpatients (n=642) receiving long-term NSAID therapy who are at risk of PU recurrence. The patients received vonoprazan (10 mg or 20 mg) or lansoprazole 15 mg once daily. For DB, non-inferiority of the proportion of patients with recurrent PU within 24 weeks was analysed by Farrington and Manning test (significance level 2.5%, non-inferiority margin 8.3%; primary endpoint), recurrent PU within 12 weeks, bleeding and time-to-event of PU (secondary endpoint) and treatment-emergent adverse events (TEAEs). For EXT, TEAEs (primary endpoint), recurrent PU and safety (secondary) were assessed up to 104 weeks for patients in the extension study.

Results The non-inferiority of vonoprazan 10 mg and 20 mg to lansoprazole 15 mg was verified (percentage difference –2.2%,95% CI –6.2% to 1.8%, p<0.001; –2.1%,95% CI –6.1% to 2.0%, p<0.001, respectively). The proportion of patients with endoscopically confirmed recurrent PU within 24 weeks was 3.3%, 3.4% and 5.5%, for vonoprazan 10 mg, 20 mg and lansoprazole 15 mg, respectively. No significant safety concerns were identified.

Conclusion The non-inferiority of vonoprazan (10 and 20 mg) was verified in patients receiving long-term NSAIDs in DB; it was effective and well tolerated in EXT for longer than 1 year, with a safety profile similar to lansoprazole (15 mg).

Trial registration numbers NCT01452750, NCT01456260; Results.

  • rheumatoid arthritis
  • lansoprazole osteoarthritis
  • NSAIDs
  • non-inferiority
  • potassium-competitive acid blockers
  • peptic ulcer
  • vonoprazan

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

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Footnotes

  • Contributors YM and KA were consultants for the clinical endpoint committee members for this study. SS was the medical adviser and TK was the medical expert for the study. KO and AN were responsible for clinical/scientific aspects of the study. NF was responsible for statistical analysis. Writing assistance was provided by content Ed Net and by Tania Dickson, PhD and Rebecca Lew, PhD, CMPP of ProScribe, Envision Pharma Group. KS was the coordinating investigator of this study.

  • Funding The study and writing assistance were funded by Takeda pharmaceutical company.

  • Competing interests YM has served as a consultant for, received grant and honorarium from Takeda Pharmaceutical Company. KO, NF and AN are employees of Takeda Pharmaceutical Company. SS has served as a consultant for and received a grant, honorarium and travel fee from Takeda Pharmaceutical Company. TK, KA and KS have served as a consultant and received a grant and honorarium from Takeda Pharmaceutical Company.

  • Patient consent Obtained.

  • Ethics approval This study is conducted in accordance with the standards of good clinical practice and incompliance with the declaration of Helsinki 2013 and local regulations, and has been submitted and approved by the institutional review boards of the study facilities.

  • Provenance and peer review Not commissioned; internally peer reviewed.

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