본문 바로가기
KERD
논문KCI 등재

Rebamipide Prevents the Hemoglobin Drop Related to Mucosal-Damaging Agents at a Level Comparable to Proton Pump Inhibitors

0

조회

0

다운로드

0

인용

0

참고문헌

키워드

초록

Background/Aims: The effect of proton pump inhibitors (PPIs) on the lower gastrointestinal (GI) tract is uncertain, with potential to worsen damage. This study aimed to find the best method for protecting the entire GI tract from mucosal damage. Methods: A retrospective cohort study at Samsung Medical Center (2002-2019) included 195,817 patients prescribed GI mucosa-damaging agents. The primary goal was to assess the effectiveness of GI protective agents in preventing significant hemoglobin drops (>2 g/dL), indicating overall GI mucosal damage. Self-controlled case series and landmark analysis were used to address biases in real-world data. Results: The incidence rate ratios for rebamipide, PPI, and histamine-2 receptor antagonist (H2RA) were 0.34, 0.33, and 0.52, respectively. Rebamipide showed a significantly lower incidence rate than H2RA and was comparable to PPIs. Landmark analysis revealed significant reductions in hemoglobin drop risk with rebamipide and H2RA, but not with PPI. Conclusions: Rebamipide, like PPIs, was highly effective in preventing blood hemoglobin level decreases, as shown in real-world data. Rebamipide could be a comprehensive strategy for protecting the entire GI tract, especially when considering PPIs' potential side effects on the lower GI tract.

Abstract

Background/Aims: The effect of proton pump inhibitors (PPIs) on the lower gastrointestinal (GI) tract is uncertain, with potential to worsen damage. This study aimed to find the best method for protecting the entire GI tract from mucosal damage. Methods: A retrospective cohort study at Samsung Medical Center (2002-2019) included 195,817 patients prescribed GI mucosa-damaging agents. The primary goal was to assess the effectiveness of GI protective agents in preventing significant hemoglobin drops (>2 g/dL), indicating overall GI mucosal damage. Self-controlled case series and landmark analysis were used to address biases in real-world data. Results: The incidence rate ratios for rebamipide, PPI, and histamine-2 receptor antagonist (H2RA) were 0.34, 0.33, and 0.52, respectively. Rebamipide showed a significantly lower incidence rate than H2RA and was comparable to PPIs. Landmark analysis revealed significant reductions in hemoglobin drop risk with rebamipide and H2RA, but not with PPI. Conclusions: Rebamipide, like PPIs, was highly effective in preventing blood hemoglobin level decreases, as shown in real-world data. Rebamipide could be a comprehensive strategy for protecting the entire GI tract, especially when considering PPIs' potential side effects on the lower GI tract.

참고문헌 (49)

  1. Lanas A, "A review of the gastrointestinal safety data: a gastroenterologist’s perspective", Rheumatology (Oxford), 49(Suppl 2), pp.ii3~ii10 (2010)
  2. Casado Arroyo R, "Lower GI bleeding is more common than upper among patients on dual antiplatelet therapy : long-term follow-up of a cohort of patients commonly using PPI cotherapy", Heart, 98, pp.718~723 (2012)
  3. Tsibouris P, "Small bowel ulcerative lesions are common in elderly NSAIDs users with peptic ulcer bleeding", World J Gastrointest Endosc, 6, pp.612~619 (2014)
  4. Shin SJ, "Non-steroidal anti-inflammatory drug-induced enteropathy", Intest Res, 15, pp.446~455 (2017)
  5. Lanza FL, "Guidelines for prevention of NSAID-related ulcer complications", Am J Gastroenterol, 104, pp.728~738 (2009)
  6. Kinoshita Y, "Advantages and disadvantages of long-term proton pump inhibitor use", J Neurogastroenterol Motil, 24, pp.182~196 (2018)
  7. Wedemeyer RS, "Pharmacokinetic drug interaction profiles of proton pump inhibitors : an update", Drug Saf, 37, pp.201~211 (2014)
  8. Yu LY, "A review of the novel application and potential adverse effects of proton pump inhibitors", Adv Ther, 34, pp.1070~1086 (2017)
  9. Koch M, "Prevention of nonsteroidal anti-inflammatory drug-induced gastrointestinal mucosal injury : a meta-analysis of randomized controlled clinical trials", Arch Intern Med, 156, pp.2321~2332 (1996)
  10. Rostom A, "Prevention of NSAIDinduced gastroduodenal ulcers", Cochrane Database Syst Rev, (4), pp.CD002296~ (2002)
  11. Satoh K, "Evidence-based clinical practice guidelines for peptic ulcer disease 2015", J Gastroenterol, 51, pp.177~194 (2016)
  12. Joo MK, "Clinical guidelines for druginduced peptic ulcer, 2020 revised edition", Korean J Gastroenterol, 76, pp.108~133 (2020)
  13. Watanabe T, "Current knowledge on non-steroidal anti-inflammatory drug-induced smallbowel damage : a comprehensive review", J Gastroenterol, 55, pp.481~495 (2020)
  14. Edogawa S, "Current topics of strategy of NSAID-induced small intestinal lesions", Digestion, 92, pp.99~107 (2015)
  15. Chan FK, "Risks of bleeding recurrence and cardiovascular events with continued aspirin use after lower gastrointestinal hemorrhage", Gastroenterology, 151, pp.271~277 (2016)
  16. Kim TJ, "Effectiveness of acid suppressants and other mucoprotective agents in reducing the risk of occult gastrointestinal bleeding in nonsteroidal antiinflammatory drug users", Sci Rep, 9, pp.11696~ (2019)
  17. Niwa Y, "Efficacy of rebamipide for diclofenac-induced small-intestinal mucosal injuries in healthy subjects : a prospective, randomized, doubleblinded, placebo-controlled, cross-over study", J Gastroenterol, 43, pp.270~276 (2008)
  18. Goldstein JL, "Haemoglobin decreases in NSAID users over time : an analysis of two large outcome trials", Aliment Pharmacol Ther, 34, pp.808~816 (2011)
  19. Laine L, "Serious lower gastrointestinal clinical events with nonselective NSAID or coxib use", Gastroenterology, 124, pp.288~292 (2003)
  20. Lanas A, "Risk factors associated with a decrease ≥2 g", dL in haemoglobin and, Aliment Pharmacol Ther, pp.2012, 36[DOI]
  21. Anderson JR, "Analysis of survival by tumor response", J Clin Oncol, 1, pp.710~719 (1983)
  22. Whitaker HJ, "Tutorial in biostatistics : the self-controlled case series method", Stat Med, 25, pp.1768~1797 (2006)
  23. Petersen I, "Self controlled case series methods : an alternative to standard epidemiological study designs", BMJ, 354, pp.i4515~ (2016)
  24. Abdul-Hussein M, "Concomitant administration of a histamine2 receptor antagonist and proton pump inhibitor enhances gastric acid suppression", Pharmacotherapy, 35, pp.1124~1129 (2015)
  25. Cho HY, "Pharmacokinetics and bioequivalence of two formulations of rebamipide 100-mg tablets : a randomized, single-dose, two-period, twosequence crossover study in healthy Korean male volunteers", Clin Ther, 31, pp.2712~2721 (2009)
  26. Hasegawa S, "Bioequivalence of rebamipide granules and tablets in healthy adult male volunteers", Clin Drug Investig, 23, pp.771~779 (2003)
  27. Dunne CL, "30-Day readmission rates among upper gastrointestinal bleeds : a systematic review and meta-analysis", J Gastroenterol Hepatol, 38, pp.692~702 (2023)
  28. Lau JY, "Timing of endoscopy for acute upper gastrointestinal bleeding", N Engl J Med, 382, pp.1299~1308 (2020)
  29. Dafni U, "Landmark analysis at the 25-year landmark point", Circ Cardiovasc Qual Outcomes, 4, pp.363~371 (2011)
  30. Rao P, "Evolution of nonsteroidal anti-inflammatory drugs(NSAIDs) : cyclooxygenase(COX)inhibition and beyond", J Pharm Pharm Sci, 11, pp.81s~110s (2008)
  31. Vane JR, "Anti-inflammatory drugs and their mechanism of action", Inflamm Res, 47(Suppl 2), pp.S78~S87 (1998)
  32. Bacchi S, "Clinical pharmacology of non-steroidal anti-inflammatory drugs : a review", Antiinflamm Antiallergy Agents Med Chem, 11, pp.52~64 (2012)
  33. Bjarnason I, "Mechanisms of damage to the gastrointestinal tract from nonsteroidal anti-inflammatory drugs", Gastroenterology, 154, pp.500~514 (2018)
  34. Lanas A, "Effect of antisecretory drugs and nitrates on the risk of ulcer bleeding associated with nonsteroidal anti-inflammatory drugs, antiplatelet agents, and anticoagulants", Am J Gastroenterol, 102, pp.507~515 (2007)
  35. Washio E, "Proton pump inhibitors increase incidence of nonsteroidal anti-inflammatory drug-induced small bowel injury : a randomized, placebocontrolled trial", Clin Gastroenterol Hepatol, 14, pp.809~815 (2016)
  36. Lo WK, "Proton pump inhibitor use and the risk of small intestinal bacterial overgrowth : a meta-analysis", Clin Gastroenterol Hepatol, 11, pp.483~490 (2013)
  37. Endo H, "Risk factors for smallbowel mucosal breaks in chronic low-dose aspirin users : data from a prospective multicenter capsule endoscopy registry", Gastrointest Endosc, 80, pp.826~834 (2014)
  38. Wallace JL, "Proton pump inhibitors exacerbate NSAID-induced small intestinal injury by inducing dysbiosis", Gastroenterology, 141, pp.1314~1322 (2011)
  39. Wallace JL, "NSAID gastropathy and enteropathy : distinct pathogenesis likely necessitates distinct prevention strategies", Br J Pharmacol, 165, pp.67~74 (2012)
  40. Otani K, "Microbiota plays a key role in non-steroidal anti-inflammatory drug-induced small intestinal damage", Digestion, 95, pp.22~28 (2017)
  41. Scarpignato C, "Safe prescribing of non-steroidal anti-inflammatory drugs in patients with osteoarthritis : an expert consensus addressing benefits as well as gastrointestinal and cardiovascular risks", BMC Med, 13, pp.55~ (2015)
  42. Snook J, "British Society of Gastroenterology guidelines for the management of iron deficiency anaemia in adults", Gut, 70, pp.2030~2051 (2021)
  43. Kim JH, "Preventive efficacy and safety of rebamipide in nonsteroidal anti-inflammatory druginduced mucosal toxicity", Gut Liver, 8, pp.371~379 (2014)
  44. Tozawa K, "A randomized, double-blind, placebo-controlled study of rebamipide for gastric mucosal injury taking aspirin with or without clopidogrel", Dig Dis Sci, 59, pp.1885~1890 (2014)
  45. Kurokawa S, "A randomized, doubleblinded, placebo-controlled, multicenter trial, healing effect of rebamipide in patients with low-dose aspirin and", or nonsteroidal anti-inflammatory drug induced small bowel injury, 2014, pp.49, 239~244
  46. Watanabe T, "A multicenter, randomized, double-blind, placebo-controlled trial of highdose rebamipide treatment for low-dose aspirin-induced moderate-to-severe small intestinal damage", PLoS One, 10, pp.e0122330~ (2015)
  47. Kurata S, "Rebamipide protects small intestinal mucosal injuries caused by indomethacin by modulating intestinal microbiota and the gene expression in intestinal mucosa in a rat model", J Clin Biochem Nutr, 56, pp.20~27 (2015)
  48. Tanigawa T, "Rebamipide inhibits indomethacin-induced small intestinal injury : possible involvement of intestinal microbiota modulation by upregulation of α-defensin 5", Eur J Pharmacol, 704, pp.64~69 (2013)
  49. Zhang WT, "Inhibition of aspirininduced gastrointestinal injury : systematic review and network meta-analysis", Front Pharmacol, 12, pp.730681~ (2021)

관련 논문AI추천

Preventive Efficacy and Safety of Rebamipide in Nonsteroidal Anti-Inflammatory Drug-Induced Mucosal Toxicity박원, 강영모, 김성국, 김정호, 류완희, 박수헌, 박용욱, 유종선, 이돈행, 이수곤, 이수택, 이용찬, 조철수거트앤리버 소화기연관학회협의회 · Gut and Liver2014 · 제8권 제4호The effect of rebamipide on non-steroidal antiinflammatory drug-induced gastro-enteropathy: a multi-center, randomized pilot study김나영, Cheol Min Shin, Dong Ho Lee, Dong Jun Oh, Eun Ha Kang, Fei Liu, Hyuk Yoon, Hyun Soo Kim, Ki-Jeoung Kim, Nayoung Kim, Yoon Jin Choi, You-Jung Ha, Young Soo Park, Yun Jong Lee대한내과학회 · The Korean Journal of Internal Medicine2022 · 제37권 제6호Efficacy and Safety of Rebamipide versus Its New Formulation, AD-203, in Patients with Erosive Gastritis: A Randomized, Double-Blind, Active Control, Noninferiority, Multicenter, Phase 3 Study고광현, 김경오, 김광하, 김병욱, 김재규, 김태년, 김현수, 박선자, 성인경, 성재규, 이동호, 임윤정, 전성우, 정일권, 조수정, Chun Hoon Jai, Jeon Han Ho, Joo Moon Kyung, Jung Sung Woo, Kim Hyungkil, Kim Ji Won, Lee Hang Lak, Lee Ok-Jae, Lee Soo Teik, Park Hong Jun, Park Jong-Jae거트앤리버 소화기연관학회협의회 · Gut and Liver2021 · 제15권 제6호Limited Effect of Rebamipide in Addition to Proton Pump Inhibitor (PPI) in the Treatment of Post-Endoscopic Submucosal Dissection Gastric Ulcers: A Randomized Controlled Trial Comparing PPI Plus Rebamipide Combination Therapy with PPI MonotherapyAkira Aso, Eikichi Ihara, Haruei Ogino, Hirotada Akiho, Kazuhiko Nakamura, Kazuya Akahoshi, Naohiko Harada, Norimoto Nakamura, Ryoichi Takayanagi, Toshiaki Ochiai, Tsutomu Iwasa, Yoichiro Iboshi거트앤리버 소화기연관학회협의회 · Gut and Liver2016 · 제10권 제6호The Role of Acid Suppressants in the Prevention of Anticoagulant-Related Gastrointestinal Bleeding: A Systematic Review and Meta-Analysis대한상부위장관. 헬리코박터학회, Beom Jin Kim, Bong Eun Lee, Byung-Wook Kim, Chang Seok Bang, Chan Hyuk Park, Hye-Kyung Jung, Hyo-Joon Yang, Jae Myung Park, Jeong Hoon Lee, Ji Yong Ahn, Joon Sung Kim, Moon Kyung Joo, Yu Kyung Cho거트앤리버 소화기연관학회협의회 · Gut and Liver2020 · 제14권 제1호A Matched Case-Control Study of a Novel Acid-Pump Antagonist and Proton-Pump Inhibitor for the Treatment of Iatrogenic Ulcers Caused by Endoscopic Submucosal Dissection김용길, 김태년, 장병익거트앤리버 소화기연관학회협의회 · Gut and Liver2010 · 제4권 제1호

이 간행물의 다른 논문 (16건)