Efficacy of rebamipide in Helicobacter pylori eradication regimens: A review of recent experimental and clinical data

The review article systematises scientific data extracted from international and domestic electronic libraries (PubMed, Scopus, eLIBRARY.RU, RSCI). The information search was conducted using the following keywords: “rebamipide”, “Helicobacter pylori eradication”, “gastroprotection”, “antibiotic resistance”, and “randomised controlled trials”. At the initial stage, 134 publications were selected. After verification against the screening criteria, 86 studies were retained. These included results from randomised controlled trials, longitudinal studies, and cohort studies. A qualitative analysis was performed on 71 articles, while a quantitative synthesis included 4 meta-analyses aggregating data from 34 primary studies. The “Introduction” section is based on 22 sources covering epidemiology and resistance trends, while the “Conclusion” section draws on 47 publications detailing the inhibition of bacterial adhesion, NF-κB modulation, cytotoxicity protection against the CagA toxin, and acceleration of mucosal repair. A total of 16 studies were excluded from the analysis due to the use of outdated treatment regimens or non-compliance with current diagnostic criteria. The final systematic review includes 57 relevant articles. It was found that under conditions of steadily increasing antibiotic resistance— particularly to clarithromycin— the adjuvant use of rebamipide significantly enhances eradication efficacy (up to 82–96%). The drug stimulates prostaglandin synthesis, restores epithelial tight junctions, suppresses oxidative stress, and reduces the expression of pro-inflammatory cytokines. The analysis confirms that the findings align with international consensus statements and the recommendations of the Russian Gastroenterological Association. Rebamipide demonstrates a favourable safety profile: it minimises the incidence of dyspeptic reactions, normalises epithelial permeability, accelerates the healing of erosive and ulcerative lesions, and promotes the regression of intestinal metaplasia in the post-eradication period. This fully justifies its integration into current clinical protocols.

1. Bordin D, Morozov S, Plavnik R, Bakulina N, Voynovan I, Skibo I et al. Helicobacter pylori infection prevalence in ambulatory settings in 2017–2019 in Russia: The data of real-world national multicenter trial. Helicobacter. 2022;27(5):e12924. https://doi.org/10.1111/hel.12924.

2. Maev IV, Andreev DN, Samsonov AA, Fomenko AK. H. pylori-associated chronic gastritis: status update on the problem. Meditsinskiy Sovet. 2022;16(15):35–45. (In Russ.) https://doi.org/10.21518/2079-701X-2022-16-15-35-45.

3. Bordin DS, Kuznetsova ES, Stauver EE, Nikol'skaya KA, Chebotareva MV, Voynovan IN, Neyasova NA. Epidemiology of Helicobacter pylori infection in the Russian Federation from 1990 to 2023: a systematic review. RMJ. Medical Review. 2024;8(5):260–267. (In Russ.) https://doi.org/10.32364/2587-6821-2024-8-5-3.

4. Zamani M, Ebrahimtabar F, Zamani V, Miller WH, Alizadeh-Navaei R, ShokriShirvani J, Derakhshan MH. Systematic review with meta-analysis: the worldwide prevalence of Helicobacter pylori infection. Aliment Pharmacol Ther. 2018;47(7):868–876. https://doi.org/10.1111/apt.14561.

5. Hooi JKY, Lai WY, Ng WK, Suen MMY, Underwood FE, Tanyingoh D et al. Global Prevalence of Helicobacter pylori Infection: Systematic Review and Meta-Analysis. Gastroenterology. 2017;153(2):420–429. https://doi.org/10.1053/j.gastro.2017.04.022.

6. Maev IV, Samsonov AA, Andreev DN, Grechushnikov VB, Korovina TI. Clinical significance of Helicobacter pylori infection. Clinical Medicine (Russian Journal). 2013;91(8):4–12. (In Russ.) Available at: https://elibrary.ru/peuivz.

7. Kato M, Asaka M. Recent development of gastric cancer prevention. Jpn J Clin Oncol. 2012;42(11):987–994. https://doi.org/10.1093/jjco/hys151.

8. Fuccio L, Zagari RM, Eusebi LH, Laterza L, Cennamo V, Ceroni L et al. Metaanalysis: can Helicobacter pylori eradication treatment reduce the risk for gastric cancer? Ann Intern Med. 2009;151(2):121–128. https://doi.org/10.7326/0003-4819-151-2-200907210-00009.

9. Lee YC, Chen TH, Chiu HM, Shun CT, Chiang H, Liu TY et al. The benefit of mass eradication of Helicobacter pylori infection: a community-based study of gastric cancer prevention. Gut. 2013;62(5):676–682. https://doi.org/10.1136/gutjnl-2012-302240.

10. Andreev DN, Bordin DS, Nikolskaya KА, Dzhafarova AR, Cherenkova VV. Current trends in Helicobacter pylori eradication therapy. Meditsinskiy Sovet. 2023;17(8):18–27. (In Russ.) https://doi.org/10.21518/ms2023-134.

11. Maev IV, Kucheryavyy YuA, Andreev DN. Helicobacter pylori antibiotic resistance: from clinical significance to molecular mechanisms. Lechaschi Vrach. 2014;(2):34. (In Russ.) Available at: https://www.lvrach.ru/2014/02/15435893.

12. Polyakova VV, Bodunova NA, Tsapkova LA, Serebryakov VV, Nikolskaya KA, Chebotareva MV et al. Impact of H. pylori Resistance to Clarithromycin on the Efficacy of First-Line Eradication Therapy Regimens: Preliminary Results of a Prospective Study. Effective Pharmakotherapy. 2025;21(22):18–23. (In Russ.) Available at: https://umedp.ru/articles/vliyanie_rezistentnosti_h_pylori_k_klaritromitsinu_na_effektivnost_eradikatsionnoy_terapii_pervoy_li.html.

13. Maev IV, Andreev DN. Molecular genetic predictors of resistance to antiHelicobacter pylori therapy. Terapevticheskii Arkhiv. 2017;89(8):5–12. (In Russ.) https://doi.org/10.17116/terarkh20178985-12.

14. Andreev DN, Maev IV, Kucheryavyy YuA. Helicobacter pylori resistance in the Russian Federation: a meta-analysis of studies over the past 10 years. Terapevticheskii Arkhiv. 2020;92(11):24–30. (In Russ.) Available at: https://ter-arkhiv.ru/0040-3660/article/view/56917.

15. Kim J, Kim K, Lee JS, Kim SY, Kim KO, Kim YJ et al. The Efficacy of Rebamipide or Ecabet Sodium Supplementation for Helicobacter pylori Eradication Therapy Compared with Quadruple (Concomitant) Regimen. Korean J Gastroenterol. 2018;71(4):204–212. (In Korean) https://doi.org/10.4166/kjg.2018.71.4.204.

16. Trukhmanov AS, Rumyantseva DE, Lapina TL. Cytoprotection of the Gastric Mucosa and Eradication Therapy of Helicobacter Pylori Infection: Points of Conjugation. Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2025;35(2):119–128. (In Russ.) https://doi.org/10.22416/1382-4376-2025-35-2-119-128.

17. Malfertheiner P, Megraud F, O'Morain CA, Atherton J, Axon AT, Bazzoli F et al. Management of Helicobacter pylori infection – the Maastricht IV/florence Consensus Report. Gut. 2012;61(5):646–664. https://doi.org/10.1136/gutjnl2012-302084.

18. Nyssen OP, Vaira D, Tepes B, Kupcinskas L, Bordin D, Pérez-Aisa Á et al. Room for Improvement in the Treatment of Helicobacter pylori Infection: Lessons from the European Registry on H. pylori Management (Hp-EuReg). J Clin Gastro­ enterol. 2022;56(2):e98–e108. https://doi.org/10.1097/MCG.0000000000001482.

19. Maev IV, Kucheryavyy YuA, Andreev DN. Modern approaches to antihelicobacter therapy optimization. Lechaschi Vrach. 2014;(4):73. (In Russ.) Available at: https://www.lvrach.ru/2014/04/15435943.

20. Bordin DS, Livzan MA, Osipenko MF, Mozgovoy SI, Andreyev DN, Maev IV. The key statements of the Maastricht VI consensus. Experimental and Clinical Gastroenterology. 2022;(9):5–21. (In Russ.) https://doi.org/10.31146/1682-8658-ecg-205-9-5-21.

21. Ivashkin VT, Maev IV, Lapina TL, Fedorov ED, Sheptulin AA, Trukhmanov AS et al. Clinical Recommendations of Russian Gastroenterological Association and RENDO Endoscopic Society on Diagnosis and Treatment of Gastritis and Duodenitis. Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2021;31(4):70–99. (In Russ.) https://doi.org/10.22416/13824376-2021-31-4-70-99.

22. Andreev DN, Maev IV, Dicheva DT, Samsonov AA, Partzvania-Vinogradova EV. Efficacy and safety of the use of rebamipide in the scheme of triple eradication therapy of Helicobacter pylori infection: a prospective randomized comparative study. Terapevticheskii Arkhiv. 2018;90(8):27–32. (In Russ.) https://doi.org/10.26442/terarkh201890827-32.

23. Lapina ТL, Ivashkin VT. Rebamipide during chronic gastritis: H. pylori eradication therapy and restoration of gastric mucosa barrier function. Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2023;33(6):81–87. (In Russ.) https://doi.org/10.22416/1382-4376-2023-33-6-81-87.

24. Babich AE, Luchinina EV, Kompaniets OG, Zubareva NA. Rebamipid in real clinical practice: quality of life and safety of use. Medical Alphabet. 2021;(35):7–11. (In Russ.) https://doi.org/10.33667/2078-5631-2021-35-7-11.

25. Bakulina NV, Tikhonov SV, Okovityi SV, Lutaenko EА, Bolshakov AO, Prikhodko VA, Nekrasova AS. Pharmacokinetics and pharmacodynamics of rebamipide. New possibilities of therapy: A review. Terapevticheskii Arkhiv. 2022;94(12):1431–1437. (In Russ.) https://doi.org/10.26442/00403660.2022.12.202000.

26. Nishizawa T, Nishizawa Y, Yahagi N, Kanai T, Takahashi M, Suzuki H. Effect of supplementation with rebamipide for Helicobacter pylori eradication therapy: a systematic review and meta-analysis. J Gastroenterol Hepatol. 2014;29(Suppl. 4):20–24. https://doi.org/10.1111/jgh.12769.

27. Andreev DN, Kucheryavyy YA. Factors of the microand macroorganism influencing the effectiveness of anti-Helicobacter pylori therapy. Consilium Medicum. Gastroenterology (Suppl.). 2013;15(8):5–9. (In Russ.) Available at: https://consilium.orscience.ru/2075-1753/article/view/93851.

28. Ivashkin VT, Maev IV, Lapina TL, Kucheryavyy YuA, Abdulkhakov SR, Alekseeva OP et al. H. pylori-Associated Gastritis, Gastritis after H. pylori Eradication and H. pylori-Negative Gastritis: Algorithm of Diagnosis and Treatment (Literature Review and Resolution of the Expert Panel of the Russian Gastroenterological Association). Russian Journal of Gastro­ enterology, Hepatology, Coloproctology. 2024;34(3):7–23. (In Russ.) https://doi.org/10.22416/1382-4376-2024-34-3-7-23.

29. Osipenko MF, Bikbulatova YeA. Rebamipide – a Gastrointestinal Protective Agent with Pleiotropic Properties. Effective Pharmacotherapy. 2016;(34):28–33. (In Russ.) Available at: https://elibrary.ru/xwuokp.

30. Sagynbaeva VE, Lazebnik LB. Rebamipide is a modern gastrocytoprotector under erosive and ulcerative injuries of upper gastrointestinal tract: results of the research. Therapy. 2019;5(8):173–180. (In Russ.) https://doi.org/10.18565/therapy.2019.8.173-183.

31. Bordin DS, Krolevets TS, Livzan MA. Are physicians ready to comply with the guidelines for diagnosis and management of Helicobacter pyloriassociated diseases: the survey results 2020–2021. Almanac of Clinical Medicine. 2021;49(7):455–468. (In Russ.) https://doi.org/10.18786/20720505-2021-49-051.

32. Dekhnich NN, Kozlova MD, Kovalenko TN. Treatment for Helicobacter pylori infection: an effective strategy. RMJ. Medical Review. 2024;8(5):281–286. (In Russ.). https://doi.org/10.32364/2587-6821-2024-8-5-6.

33. Ageeva EA, Alekseenko SA, Martynyuk MV, Vorobyova VA. Experience in using various regimens for eradication of Helicobacter pylori infection in patients who had COVID-19 and received antibacterial therapy. Public Health of the Far East. 2025;(2):36–41. (In Russ.) https://doi.org/10.33454/ 1728-1261-2025-2-36-41.

34. Maev IV, Andreev DN, Samsonov AA, Cheryomushkina AS. Peptic ulcer: the current state of the problem. Meditsinskiy Sovet. 2022;16(6):100–108. (In Russ.) https://doi.org/10.21518/2079-701X-2022-16-6-100-108.

35. Andreev DN, Maev IV. Rebamipide: evidence base for use in gastroenterology. Terapevticheskii Arkhiv. 2020;92(12):97–104. (In Russ.) https://doi.org/10.26442/00403660.2020.12.200455.

36. Hahm KB, Lee KJ, Kim YS, Kim JH, Cho SW, Yim H, Joo HJ. Quantitative and qualitative usefulness of rebamipide in eradication regimen of Helicobacter pylori. Dig Dis Sci. 1998;43(9 Suppl.):192S–197S. Available at: https://pubmed.ncbi.nlm.nih.gov/9753249/.

37. Lee JS, Jeon SW, Lee HS, Kwon YH, Nam SY, Bae HI, Seo AN. Rebamipide for the Improvement of Gastric Atrophy and Intestinal Metaplasia: A Prospective, Randomized, Pilot Study. Dig Dis Sci. 2022;67(6):2395–2402. https://doi.org/10.1007/s10620-021-07038-7.

38. Haruma K, Ito M, Kido S, Manabe N, Kitadai Y, Sumii M et al. Long-term rebamipide therapy improves Helicobacter pylori-associated chronic gastritis. Dig Dis Sci. 2002;47(4):862–867. https://doi.org/10.1023/a:1014716822702.

39. Trukhmanov AS, Rumyantseva DE. Rebamipide and proton pump inhibitors: benefits of combined use. Pediatric Nutrition. 2022;20(1):42–51. (In Russ.) https://doi.org/10.20953/1727-5784-2022-1-42-51.

40. Fujioka T, Arakawa T, Shimoyama T, Yoshikawa T, Itoh M, Asaka M et al. Effects of rebamipide, a gastro-protective drug on the Helicobacter pylori status and inflammation in the gastric mucosa of patients with gastric ulcer: a randomized double-blind placebo-controlled multicentre trial. Aliment Pharmacol Ther. 2003;18(Suppl. 1):146–152. https://doi.org/10.1046/j.1365-2036.18.s1.20.x.

41. Lee KH, Kim JY, Kim WK, Shin DH, Choi KU, Kim DW et al. Protective effect of rebamipide against Helicobacter pylori-CagA-induced effects on gastric epithelial cells. Dig Dis Sci. 2011;56(2):441–448. https://doi.org/10.1007/s10620-010-1299-x.

42. Simanenkov VI, Bakulina NV, Fil TS, Khubieva AKh. Evaluation of efficiency of H. pylori eradication in case of addition of cytoprotective preparation rebamipide to the treatment: results of the bastion trial. Farmateka. 2017;(5S):65–71. (In Russ.) Available at: https://pharmateca.ru/articles/Ocenka-effektivnostieradikacii-H-pylori-pri-dobavlenii-k-sheme-lecheniya-citoprotektivnogopreparata-rebamipid-rezultaty-issledovaniya-BASTION.html.

43. Kak M. Rebamipide in gastric mucosal protection and healing: An Asian perspective. World J Gastrointest Pharmacol Ther. 2025;16(1):101753. https://doi.org/10.4292/wjgpt.v16.i1.101753.

44. Korobeynikova ER, Shkatova EYu. The treatment of Helicobacter pyloriassociated erosive lesions of gastroduodenal zone with the use of interactive learning technologies and rebamipide in young men. Experimental and Clinical Gastroenterology. 2019;169(9):27–31. (In Russ.) https://doi.org/10.31146/1682-8658-ecg-169-9-27-31.

45. Andreev DN, Maev IV, Dicheva DT. Efficiency of the Inclusion of Rebamipide in the Eradication Therapy for Helicobacter pylori Infection: Meta-Analysis of Randomized Controlled Studies. J Clin Med. 2019;8(9):1498. https://doi.org/10.3390/jcm8091498.

46. Andreev DN, Maev IV, Bordin DS, Lyamina SV, Dicheva DT, Fomenko AK, Bagdasarian AS. Effectiveness of Rebamipide as a part of the Helicobacter pylori eradication therapy in Russia: a meta-analysis of controlled trials. Consilium Medicum. 2022;24(5):333–338. (In Russ.) Consilium Medicum. 2022;24(5):333–338. https://doi.org/10.26442/20751753.2022.5.201863.

47. Bakulina NV, Ponomarenko VA, Kerimova ASh, Thai Hien T, Shihmagomedova ASh, Veliev AM, Savilova IV. The high-dose dual therapy for eradication of Helicobacter pylori: efficacy and safety. Terapevticheskii Arkhiv. 2025;97(8):642–650. (In Russ.) https://doi.org/10.26442/00403660.2025.08.203300.

48. Andreev DN, Khurmatullina AR, Maev IV, Bordin DS, Zaborovskiy AV, Abdulkhakov SR et al. Helicobacter pylori Antibiotic Resistance in Russia: A Systematic Review and Meta-Analysis. Antibiotics. 2025;14(5):524. https://doi.org/10.3390/antibiotics14050524.

49. Maev IV, Khurmatullina AR, Andreev DN, Zaborovsky AV, Kucheryavyy YA, Sokolov PS, Beliy PA. Rebamipide as an Adjunctive Therapy for Gastrointestinal Diseases: An Umbrella Review. Pharmaceuticals. 2026;19(1):144. https://doi.org/10.3390/ph19010144.

50. Terano A, Arakawa T, Sugiyama T, Suzuki H, Joh T, Yoshikawa T et al. Rebamipide, a gastro-protective and anti-inflammatory drug, promotes gastric ulcer healing following eradication therapy for Helicobacter pylori in a Japanese population: a randomized, double-blind, placebo-controlled trial. J Gastroenterol. 2007;42(8):690–693. https://doi.org/10.1007/s00535-007-2076-2.

51. Song KH, Lee YC, Fan DM, Ge ZZ, Ji F, Chen MH et al. Healing effects of rebamipide and omeprazole in Helicobacter pylori-positive gastric ulcer patients after eradication therapy: a randomized double-blind, multinational, multi institutional comparative study. Digestion. 2011;84(3):221–229. https://doi.org/10.1159/000329353.

52. Kamada T, Sato M, Tokutomi T, Watanabe T, Murao T, Matsumoto H et al. Rebamipide improves chronic inflammation in the lesser curvature of the corpus after Helicobacter pylori eradication: a multicenter study. Biomed Res Int. 2015;2015:865146. https://doi.org/10.1155/2015/865146.

53. Magomedova PM, Mirzoeva RZ. The effectiveness of various schemes of eradication therapy in the treatment of peptic ulcer of the stomach and duodenum. International Journal of Medicine and Psychology. 2023;6(1):167–171. (In Russ.) Available at: https://elibrary.ru/vydiwi.

54. Vinogradova MV, Skvortsova EM, Skvortsov VV, Karchevsky AA. The syndrome of increased epithelial permeability and its modern pharmacological correction (clinical lecture). Archives of Clinical and Experimental Medicine. 2024;33(4):54–59. (In Russ.) Available at: https://elibrary.ru/aznslz.

55. Andreev DN, Khurmatullina AR, Maev IV, Bordin DS, Abdulkhakov SR, Kucheryavyy YA et al. The Prevalence of Helicobacter pylori Infection in the Adult Population of Russia: A Systematic Review and Meta-Analysis. Epidemiologia. 2025;6(3):47. https://doi.org/10.3390/epidemiologia6030047.

56. Andreev DN, Khurmatullina AR, Bordin DS, Maev IV. Trends in the prevalence of Helicobacter pylori infection among adults in Moscow: a systematic review and meta-analysis. Terapevticheskii Arkhiv. 2025;97(5):463–470. (In Russ.) https://doi.org/10.26442/00403660.2025.05.203250.

57. Han X, Jiang K, Wang B, Zhou L, Chen X, Li S. Effect of Rebamipide on the Premalignant Progression of Chronic Gastritis: A Randomized Controlled Study. Clin Drug Investig. 2015;35(10):665–673. https://doi.org/10.1007/s40261-015-0329-z.

58. Tsukanov VV, Amelchugova OS, Kasparov EV, Butorin NN, Vasyutin AV, Tonkikh YuL, Tretyakova OV. Role of Helicobacter pylori eradication in the prevention of gastric cancer. Terapevticheskii Arkhiv. 2014;86(8):124–127. (In Russ.) Available at: https://www.mediasphera.ru/issues/ terapevticheskij-arkhiv/2014/8/030040-36602014823.

59. Kovalenko TN, Dekhnich NN, Tryapyshko AA, Shadrina NE, Tsapkova LA, Bordin DS. Relevance of the Taipei Consensus key provisions. Effective Pharmacotherapy. 2023;19(8):66–74. (In Russ.) Available at: https://elibrary.ru/jzoyau.

60. Bakulin IG, Sushilova AG, Zharkov AV, Malkov VA. Effectiveness of 6-Month Rebamipide Therapy in Chronic Atrophic Gastritis: Results of the OPLOT Study. Effective Pharmacotherapy. 2024;20(46):28–34. (In Russ.) Available at: https://elibrary.ru/lhqcds.