Induction of Remission in Autoimmune Hepatitis With Azathioprine vs. MMF

Summary

The goal of this clinical trial is to determine the effectiveness of azathioprine (AZA) versus mycophenolate mofetil (MMF) in inducing remission in treatment-naive patients with autoimmune hepatitis (AIH). The main questions it aims to answer are: Does MMF combined with prednisolone lead to higher remission rates compared to AZA with prednisolone after 24 weeks? Is MMF associated with fewer adverse events than AZA in these patients? Researchers will compare two treatment arms (MMF vs. AZA) to see if MMF leads to improved remission rates and safety outcomes. Primary Outcome Measure: Biochemical remission: The primary outcome is the normalization of liver enzymes (AST, ALT) and IgG levels at 24 weeks. Secondary Outcome Measures: Safety and adverse events: Monitoring and comparing the incidence and severity of side effects between the two groups. Treatment adherence: Evaluating how well patients stick to their assigned treatment regimens. Improvement in quality of life: Assessing changes in the patient's quality of life using validated questionnaires. Reversal of fibrosis: Measured by liver stiffness using Fibroscan, aiming for no progression of fibrosis. Participants will: Receive either MMF or AZA, alongside a tapering dose of prednisolone. Be monitored regularly through clinic visits, laboratory tests, and safety assessments to track remission and any adverse events.

Timeline

Start

2024-11-01

Primary completion

2025-12-31

Completion

2025-12-31

Publications

• Background Snijders RJALM, Stoelinga AEC, Gevers TJG, Pape S, Biewenga M, Tushuizen ME, Verdonk RC, de Jonge HJM, Vrolijk JM, Bakker SF, Vanwolleghem T, de Boer YS, Baven Pronk MAMC, Beuers U, van der Meer AJ, Gerven NMFV, Sijtsma MGM, van Eijck BC, van IJzendoorn MC, van Herwaarden M, van den Brand FF, Korkmaz KS, van den Berg AP, Guichelaar MMJ, Levens AD, van Hoek B, Drenth JPH; Dutch Autoimmune Hepatitis Working Group. An open-label randomised-controlled trial of azathioprine vs. mycophenolate mofetil for the induction of remission in treatment-naive autoimmune hepatitis. J Hepatol. 2024 Apr;80(4):576-585. doi: 10.1016/j.jhep.2023.11.032. Epub 2023 Dec 14.
• Background Santiago P, Schwartz I, Tamariz L, Levy C. Systematic review with meta-analysis: mycophenolate mofetil as a second-line therapy for autoimmune hepatitis. Aliment Pharmacol Ther. 2019 Apr;49(7):830-839. doi: 10.1111/apt.15157. Epub 2019 Feb 13.
• Background Manns MP, Woynarowski M, Kreisel W, Lurie Y, Rust C, Zuckerman E, Bahr MJ, Gunther R, Hultcrantz RW, Spengler U, Lohse AW, Szalay F, Farkkila M, Prols M, Strassburg CP; European AIH-BUC-Study Group. Budesonide induces remission more effectively than prednisone in a controlled trial of patients with autoimmune hepatitis. Gastroenterology. 2010 Oct;139(4):1198-206. doi: 10.1053/j.gastro.2010.06.046. Epub 2010 Jun 22.
• Background Manns MP, Czaja AJ, Gorham JD, Krawitt EL, Mieli-Vergani G, Vergani D, Vierling JM; American Association for the Study of Liver Diseases. Diagnosis and management of autoimmune hepatitis. Hepatology. 2010 Jun;51(6):2193-213. doi: 10.1002/hep.23584. No abstract available.
• Background Czaja AJ. Current and future treatments of autoimmune hepatitis. Expert Rev Gastroenterol Hepatol. 2009 Jun;3(3):269-91. doi: 10.1586/egh.09.15.
• Background Terziroli Beretta-Piccoli B, Mieli-Vergani G, Vergani D. Autoimmune hepatitis: Standard treatment and systematic review of alternative treatments. World J Gastroenterol. 2017 Sep 7;23(33):6030-6048. doi: 10.3748/wjg.v23.i33.6030.
• Background Sarin SK, Kumar M, Lau GK, Abbas Z, Chan HL, Chen CJ, Chen DS, Chen HL, Chen PJ, Chien RN, Dokmeci AK, Gane E, Hou JL, Jafri W, Jia J, Kim JH, Lai CL, Lee HC, Lim SG, Liu CJ, Locarnini S, Al Mahtab M, Mohamed R, Omata M, Park J, Piratvisuth T, Sharma BC, Sollano J, Wang FS, Wei L, Yuen MF, Zheng SS, Kao JH. Asian-Pacific clinical practice guidelines on the management of hepatitis B: a 2015 update. Hepatol Int. 2016 Jan;10(1):1-98. doi: 10.1007/s12072-015-9675-4. Epub 2015 Nov 13.
• Background Makol A, Watt KD, Chowdhary VR. Autoimmune hepatitis: a review of current diagnosis and treatment. Hepat Res Treat. 2011;2011:390916. doi: 10.1155/2011/390916. Epub 2011 May 15.
• Background Czaja AJ, Freese DK; American Association for the Study of Liver Disease. Diagnosis and treatment of autoimmune hepatitis. Hepatology. 2002 Aug;36(2):479-97. doi: 10.1053/jhep.2002.34944. No abstract available.

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