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Digestive Diseases and Sciences

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30.09.2022 | Original Article

Efficacy and Safety of Bezafibrate Alone or in Combination with Ursodeoxycholic Acid in Primary Biliary Cholangitis: Systematic Review and Meta-Analysis

verfasst von: Nidah Shabbir Khakoo, Shahnaz Sultan, John M. Reynolds, Cynthia Levy

Erschienen in: Digestive Diseases and Sciences | Ausgabe 4/2023

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Abstract

Background

Bezafibrate (BZF) alone or in combination with ursodeoxycholic acid (UDCA) has been used to slow disease progression in patients with primary biliary cholangitis (PBC). We performed a systematic review and meta-analysis to assess the efficacy and harms of BZF monotherapy or combination therapy.

Methods

We performed a systematic search of PubMed, EMBASE, Cochrane Library, Scopus, ClinicalTrials.gov, and WHO ICTRP from inception until January 2020, for randomized controlled clinical trials assessing BZF + UDCA versus UDCA monotherapy or BZF monotherapy versus UDCA monotherapy in PBC patients. Additionally, we systematically evaluated data on harms using seven observational studies. Pooled effect estimates were calculated for the outcomes of interest. The certainty of evidence was assessed using GRADE (Grading of Recommendations Assessment, Development and Evaluation).

Results

We identified 7 randomized controlled trials with a total of 279 participants. Comparing BZF + UDCA to UDCA alone, a clinically significant improvement was observed in serum ALP with a mean difference (MD) of − 159.04 U/L (95% CI − 186.45 to − 131.62) and a reduction in gamma-glutamyltransferase (GGT) (MD − 106.94 IU/L; 95% CI − 151.99 to − 61.89), but not in total bilirubin (TB) or IgM levels. A statistically significant reduction in ALP levels was also noticed with BZF monotherapy compared to UDCA monotherapy. The effect of BZF + UDCA versus UDCA on mortality remains unclear. Across 5 observational studies including 106 patients, one death was reported due to advanced liver disease in an incomplete responder getting treatment with BZF + UDCA. Analysis of observational studies demonstrated improvement in pruritus intensity with BZF.

Conclusions

Use of BZF alone or in combination with UDCA improved liver biochemistries in patients with PBC, but its effect on mortality, liver-related complications or quality of life remains unknown.

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Murillo Perez CF, Goet JC, Lammers WJ et al. Milder disease stage in patients with primary biliary cholangitis over a 44-year period: a changing natural history. Hepatology 2018;67:1920–1930. https://doi.org/10.1002/hep.29717.CrossRefPubMed

Goel A, Kim WR. Natural history of primary biliary cholangitis in the ursodeoxycholic acid era: role of scoring systems. Clin Liver Dis 2018;22:563–578. https://doi.org/10.1016/j.cld.2018.03.007.CrossRefPubMed

Imam MH, Lindor KD. The natural history of primary biliary cirrhosis. Semin Liver Dis 2014;34:329–333. https://doi.org/10.1055/s-0034-1383731.CrossRefPubMed

Corpechot C, Chazouilleres O, Rousseau A et al. A placebo-controlled trial of bezafibrate in primary biliary cholangitis. N Engl J Med 2018;378:2171–2181. https://doi.org/10.1056/NEJMoa1714519.CrossRefPubMed

Hazzan R, Tur-Kaspa R. Bezafibrate treatment of primary biliary cirrhosis following incomplete response to ursodeoxycholic acid. J Clin Gastroenterol 2010;44:371–373. https://doi.org/10.1097/MCG.0b013e3181c115b3.CrossRefPubMed

Lindor KD, Bowlus CL, Boyer J, Levy C, Mayo M. Primary Biliary Cholangitis: 2018 Practice Guidance from the American Association for the Study of Liver Diseases. Hepatology 2019;69:394–419. https://doi.org/10.1002/hep.30145.CrossRefPubMed

Lammers WJ, Van Buuren HR, Hirschfield GM et al. Levels of alkaline phosphatase and bilirubin are surrogate end points of outcomes of patients with primary biliary cirrhosis: an international follow-up study. Gastroenterology 2014;147:1338-1349.e5. https://doi.org/10.1053/j.gastro.2014.08.029.CrossRefPubMed

Parés A, Caballería L, Rodés J. Excellent long-term survival in patients with primary biliary cirrhosis and biochemical response to ursodeoxycholic acid. Gastroenterology 2006;130:715–720. https://doi.org/10.1053/j.gastro.2005.12.029.CrossRefPubMed

Wetten A, Jones DEJ, Dyson JK. Specific considerations for the management of primary biliary cholangitis: are the drug treatment options good enough? Expert Opin Pharmacother 2021;22:1949–1953. https://doi.org/10.1080/14656566.2021.1940135.CrossRefPubMed

10.

Honda A, Ikegami T, Nakamuta M et al. Anticholestatic effects of bezafibrate in patients with primary biliary cirrhosis treated with ursodeoxycholic acid. Hepatology 2013;57:1931–1941. https://doi.org/10.1002/hep.26018.CrossRefPubMed

11.

Reig A, Sesé P, Parés A. Effects of bezafibrate on outcome and pruritus in primary biliary cholangitis with suboptimal ursodeoxycholic acid response. Am J Gastroenterol 2018;113:49–55. https://doi.org/10.1038/ajg.2017.287.CrossRefPubMed

12.

Yin Q, Li J, Xia Y et al. Systematic review and meta-analysis: Bezafibrate in patients with primary biliary cirrhosis. Drug Des Devel Ther 2015;9:5407–5419. https://doi.org/10.2147/DDDT.S92041.CrossRefPubMedPubMedCentral

13.

Agrawal R, Majeed M, Attar BM et al. Effectiveness of bezafibrate and ursodeoxycholic acid in patientwith primary biliary cholangitis: a meta-analysis of randomized controlled trials. Ann Gastroenterol 2019;32:489–497. https://doi.org/10.20524/aog.2019.0403.CrossRefPubMedPubMedCentral

14.

Chou R, Aronson N, Atkins D, Ismaila A, Santaguida P. Methods reference guide for effectiveness and comparative effectiveness reviews assessing harms when comparing medical interventions. Agency Healthc Res Qual. 2008.

15.

Page M, Moher D, Bossuyt P. PRISMA 2020 explanation and elaboration: updated guidance and exemplars for reporting systematic reviews. BMJ. 2021. https://doi.org/10.1136/bmj.n160.CrossRefPubMedPubMedCentral

16.

Rethlefsen M, Kirtley S, Waffenschmidt S. PRISMA-S: an extension to the PRISMA statement for reporting literature searches in systematic reviews. Syst Rev. 2021. https://doi.org/10.1186/s13643-020-01542-z.CrossRefPubMedPubMedCentral

17.

Lefebvre CG, Briscoe S, Littlewood A, et al. Chapter 4: Searching for and selecting studies in Cochrane Handbook for Systematic Reviews of Interventions. In: Version 6.0.

18.

Glanville J, Foxlee R, Wisniewski S, Noel-Storr A, Edwards M, Dooley G. Translating the Cochrane EMBASE RCT filter from the Ovid interface to Embase.com: a case study. Heal Info Libr J 2019;36:264–277.CrossRef

19.

Furlan A, Irvin E, Bombardier C. Limited search strategies were effective in finding relevant nonrandomized studies. J Clin Epidemiol 2006;59:1303–1311.CrossRefPubMed

20.

Scottish Intercollegiate Guidelines Network (SIGN). Search Filters: Observational Studies.

21.

Endnote X8. 2013.

22.

Covidence Systematic Review Software.

23.

Rohatgi A. WebPlotDigitizer Version 4.3. 2020.

24.

Higgins JPT, Altman DG, Gøtzsche PC et al. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ 2011;343:d5928–d5928. https://doi.org/10.1136/bmj.d5928.CrossRefPubMedPubMedCentral

25.

Schünemann H, Brożek J, Guyatt G, Oxman A. GRADE Handbook.

26.

Schünemann HJ. GRADEpro. [Computer Program].

27.

Review Manager (RevMan) [Computer Program]. The Nordic Cochrane Center, The Cochrane Collaboration.

28.

Hunter JE, Schmidt FL. Fixed effects vs. random effects meta-analysis models: implications for cumulative research knowledge. Int J Sel Assess 2000;8:275–292. https://doi.org/10.1111/1468-2389.00156.CrossRef

29.

Guyatt GH, Ebrahim S, Alonso-Coello P et al. GRADE guidelines 17: assessing the risk of bias associated with missing participant outcome data in a body of evidence. J Clin Epidemiol 2017;87:14–22. https://doi.org/10.1016/j.jclinepi.2017.05.005.CrossRefPubMed

30.

Higgins J, Lasserson T, Chandler J, et al. Methodological Expectations of Cochrane Intervention Reviews. 6.1. The Cochrane Collaboration; 2021.

31.

Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 2021;372:n71. https://doi.org/10.1136/bmj.n71.CrossRefPubMedPubMedCentral

32.

Hosonuma K, Sato K, Yamazaki Y et al. A prospective randomized controlled study of long-term combination therapy using ursodeoxycholic acid and bezafibrate in patients with primary biliary cirrhosis and dyslipidemia. Am J Gastroenterol 2015;110:423–431. https://doi.org/10.1038/ajg.2015.20.CrossRefPubMed

33.

Itakura J, Izumi N, Nishimura Y et al. Prospective randomized crossover trial of combination therapy with bezafibrate and UDCA for primary biliary cirrhosis. Hepatol Res 2004;29:216–222. https://doi.org/10.1016/j.hepres.2004.04.001.CrossRefPubMed

34.

Iwasaki S, Ohira H, Nishiguchi S et al. The efficacy of ursodeoxycholic acid and bezafibrate combination therapy for primary biliary cirrhosis: a prospective, multicenter study. Hepatol Res 2008;38:557–564. https://doi.org/10.1111/j.1872-034X.2007.00305.x.CrossRefPubMed

35.

Kanda T, Yokosuka O, Imazeki F, Saisho H. Bezafibrate treatment: a new medical approach for PBC patients? J Gastroenterol 2003;38:573–578. https://doi.org/10.1007/s00535-002-1102-7.CrossRefPubMed

36.

Nakai S, Masaki T, Kurokohchi K, Deguchi A, Nishioka M. Combination therapy of bezafibrate and ursodeoxycholic acid in primary biliary cirrhosis: a preliminary study. Am J Gastroenterol 2000;95:326–327. https://doi.org/10.1111/j.1572-0241.2000.01667.x.CrossRefPubMed

37.

Kurihara T, Niimi A, Maeda A, Shigemoto M, Yamashita K. Bezafibrate in the treatment of primary biliary cirrhosis: comparison with ursodeoxycholic acid. Am J Gastroenterol 2000;95:2990–2992. https://doi.org/10.1111/j.1572-0241.2000.03220.x.CrossRefPubMed

38.

Takeuchi Y, Ikeda F, Fujioka S et al. Additive improvement induced by bezafibrate in patients with primary biliary cirrhosis showing refractory response to ursodeoxycholic acid. J Gastroenterol Hepatol 2011;26:1395–1401. https://doi.org/10.1111/j.1440-1746.2011.06737.x.CrossRefPubMed

39.

Iwasaki S, Tsuda K, Ueta H et al. Bezafibrate may have a beneficial effect in pre-cirrhotic primary biliary cirrhosis. Hepatol Res 1999;16:12–18. https://doi.org/10.1016/S1386-6346(99)00033-9.CrossRef

40.

Ohmoto K, Mitsui Y, Yamamoto S. Letter to the Editor Effect of bezafibrate in primary biliary cirrhosis : a pilot study. Liver 2001;21:223–224.CrossRefPubMed

41.

Weber-Freissmuth C, Kozbial K, Staettermayer A, Beinhardt S. Effect of fibrate-add-on treatment in primary biliary cholangitis patients with an insufficient response to ursodeoxycholic acid (UDCA).

42.

Kita R, Takamatsu S, Kimura T, Kokuryu H, Osaki Y, Tomono N. Bezafibrate may attenuate biliary damage associated with chronic liver diseases accompanied by high serum biliary enzyme levels. J Gastroenterol 2006;41:686–692. https://doi.org/10.1007/s00535-006-1831-0.CrossRefPubMed

43.

Feng BL, Yu HH, Shen W. Ursodeoxycholic acid combined with bezafibrate in the treatment of refractory primary biliary cholangitis: a meta-analysis. Chin J Hepatol 2019;27:304–311. https://doi.org/10.3760/cma.j.issn.1007-3418.2019.04.012.CrossRef

44.

Peinemann F, Labeit AM, Thielscher C, Pinkawa M. Failure to address potential bias in non-randomised controlled clinical trials may cause lack of evidence on patientreported outcomes: a method study. BMJ Open. 2014. https://doi.org/10.1136/bmjopen-2013-004720.CrossRefPubMedPubMedCentral

45.

Zhu GQ, Shi KQ, Huang S et al. Network meta-analysis of randomized controlled trials: Efficacy and safety of UDCA-based therapies in primary biliary cirrhosis. Med (United States) 2015;94:e609. https://doi.org/10.1097/MD.0000000000000609.CrossRef

46.

Ramachandran A, Chamukuttan S, Shetty SA, Arun N, Susairaj P. Obesity in Asia—is it different from rest of the world. Diabetes Metab Res Rev 2012;28:47–51. https://doi.org/10.1002/dmrr.2353.CrossRefPubMed

47.

Ahmad J, Odin JA, Hayashi PH et al. Identification and characterization of fenofibrate-induced liver injury. Dig Dis Sci 2017;62:3596–3604. https://doi.org/10.1007/s10620-017-4812-7.CrossRefPubMedPubMedCentral

48.

Carrion AF, Lindor KD, Levy C. Safety of fibrates in cholestatic liver diseases. Liver Int 2021;41:1335–1343. https://doi.org/10.1111/liv.14871.CrossRefPubMed

49.

Honda A, Tanaka A, Kaneko T et al. Bezafibrate improves GLOBE and UK-PBC scores and long-term outcomes in patients with primary biliary cholangitis. Hepatology 2019;70:2035–2046. https://doi.org/10.1002/hep.30552.CrossRefPubMed

50.

Cheung AC, Kowgier M, Feld JJ. Editorial: fenofibrate as second-line therapy in high risk PBC–more answers or more questions? Authors’ reply. Aliment Pharmacol Ther 2016;43:649–650. https://doi.org/10.1111/apt.13519.CrossRefPubMed

51.

Tanaka A, Hirohara J, Nakano T et al. Association of bezafibrate with transplant-free survival in patients with primary biliary cholangitis. J Hepatol. 2021. https://doi.org/10.1016/j.jhep.2021.04.010.CrossRefPubMed

52.

Culver E, Hayden J, Thorburn D et al. S1271: obeticholic acid and bezafibrate in primary biliary cholangitis: a comparative evaluation of efficacy through real world clinical practice. Hepatology 2019;70:188–1382. https://doi.org/10.1002/hep.30941.CrossRef

53.

Sorda JA, González Ballerga E, Barreyro FJ et al. Bezafibrate therapy in primary biliary cholangitis refractory to ursodeoxycholic acid: a longitudinal study of paired liver biopsies at 5 years of follow up. Aliment Pharmacol Ther 2021;54:1202–1212. https://doi.org/10.1111/apt.16618.CrossRefPubMed

54.

Chascsa DMH, Lindor KD. Emerging therapies for PBC. J Gastroenterol 2020;55:261–272. https://doi.org/10.1007/s00535-020-01664-0.CrossRefPubMedPubMedCentral

Titel: Efficacy and Safety of Bezafibrate Alone or in Combination with Ursodeoxycholic Acid in Primary Biliary Cholangitis: Systematic Review and Meta-Analysis
verfasst von: Nidah Shabbir Khakoo
Shahnaz Sultan
John M. Reynolds
Cynthia Levy
Publikationsdatum: 30.09.2022
Verlag: Springer US
Erschienen in: Digestive Diseases and Sciences / Ausgabe 4/2023
Print ISSN: 0163-2116
Elektronische ISSN: 1573-2568
DOI: https://doi.org/10.1007/s10620-022-07704-4

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Efficacy and Safety of Bezafibrate Alone or in Combination with Ursodeoxycholic Acid in Primary Biliary Cholangitis: Systematic Review and Meta-Analysis

Abstract

Background

Methods

Results

Conclusions

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