Assessing the efficacy and safety of mycophenolate mofetil versus azathioprine in patients with autoimmune hepatitis (CAMARO trial): study protocol for a randomised controlled trial
Romée J. A. L. M. Snijders,
Anna E. C. Stoelinga,
Tom J. G. Gevers,
Simon Pape,
Maaike Biewenga,
Robert C. Verdonk,
Hendrik J. M. de Jonge,
Jan Maarten Vrolijk,
Sjoerd F. Bakker,
Thomas Vanwolleghem,
Ynto S. de Boer,
Martine A. M. C. Baven Pronk,
Ulrich H. W. Beuers,
Adriaan J. van der Meer,
Nicole M. F. van Gerven,
Marijn G. M. Sijtsma,
Bart J. Verwer,
Ingrid A. M. Gisbertz,
Maartje Bartelink,
Floris F. van den Brand,
Kerem Sebib Korkmaz,
Aad P. van den Berg,
Maureen M. J. Guichelaar,
Khalida Soufidi,
Amar D. Levens,
Bart van Hoek,
Joost P. H. Drenth,
on behalf of the Dutch Autoimmune Hepatitis Working Group
Affiliations
Romée J. A. L. M. Snijders
Department of Gastroenterology and Hepatology, Radboud University Medical Center
Anna E. C. Stoelinga
Department of Gastroenterology and Hepatology, Leiden University Medical Center
Tom J. G. Gevers
Department of Gastroenterology and Hepatology, Radboud University Medical Center
Simon Pape
Department of Gastroenterology and Hepatology, Radboud University Medical Center
Maaike Biewenga
Department of Gastroenterology and Hepatology, Leiden University Medical Center
Robert C. Verdonk
Department of Gastroenterology and Hepatology, St. Antonius Hospital
Hendrik J. M. de Jonge
Department of Gastroenterology and Hepatology, Jeroen Bosch Hospital
Jan Maarten Vrolijk
Department of Gastroenterology and Hepatology, Rijnstate Hospital
Sjoerd F. Bakker
Department of Gastroenterology and Hepatology, Elisabeth-Tweesteden Hospital
Thomas Vanwolleghem
Department of Gastroenterology and Hepatology, Antwerp University Hospital
Ynto S. de Boer
European Reference Network RARE-LIVER
Martine A. M. C. Baven Pronk
Department of Gastroenterology and Hepatology, Groene Hart Hospital
Ulrich H. W. Beuers
European Reference Network RARE-LIVER
Adriaan J. van der Meer
Department of Gastroenterology and Hepatology, Erasmus University Medical Center
Nicole M. F. van Gerven
Department of Gastroenterology and Hepatology, Rode Kruis Hospital
Marijn G. M. Sijtsma
Department of Gastroenterology and Hepatology, St. Jansdal Hospital
Bart J. Verwer
Department of Gastroenterology and Hepatology, Spaarne Gasthuis
Ingrid A. M. Gisbertz
Department of Gastroenterology and Hepatology, Hospital Bernhoven
Maartje Bartelink
Department of Gastroenterology and Hepatology, Deventer Hospital
Floris F. van den Brand
Department of Gastroenterology and Hepatology, OLVG Oost
Kerem Sebib Korkmaz
Department of Gastroenterology and Hepatology, IJselland Hospital
Aad P. van den Berg
Department of Gastroenterology and Hepatology, University Medical Center Groningen
Maureen M. J. Guichelaar
Department of Gastroenterology and Hepatology, Medisch Spectrum Twente
Khalida Soufidi
Department of Gastroenterology and Hepatology, Zuyderland
Amar D. Levens
Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center
Bart van Hoek
Department of Gastroenterology and Hepatology, Leiden University Medical Center
Joost P. H. Drenth
Department of Gastroenterology and Hepatology, Radboud University Medical Center
on behalf of the Dutch Autoimmune Hepatitis Working Group
Abstract Background Currently, the standard therapy for autoimmune hepatitis (AIH) consists of a combination of prednisolone and azathioprine. However, 15% of patients are intolerant to azathioprine which necessitates cessation of azathioprine or changes in therapy. In addition, not all patients achieve complete biochemical response (CR). Uncontrolled data indicate that mycophenolate mofetil (MMF) can induce CR in a majority of patients. Better understanding of first-line treatment and robust evidence from randomised clinical trials are needed. The aim of this study was to explore the potential benefits of MMF as compared to azathioprine, both combined with prednisolone, as induction therapy in a randomised controlled trial in patients with treatment-naive AIH. Methods CAMARO is a randomised (1:1), open-label, parallel-group, multicentre superiority trial. All patients with AIH are screened for eligibility. Seventy adult patients with AIH from fourteen centres in the Netherlands and Belgium will be randomised to receive MMF or azathioprine. Both treatment arms will start with prednisolone as induction therapy. The primary outcome is biochemical remission, defined as serum levels of alanine aminotransferase and immunoglobulin G below the upper limit of normal. Secondary outcomes include safety and tolerability of MMF and azathioprine, time to remission, changes in Model For End-Stage Liver Disease (MELD)-score, adverse events, and aspects of quality of life. The study period will last for 24 weeks. Discussion The CAMARO trial investigates whether treatment with MMF and prednisolone increases the proportion of patients in remission compared with azathioprine and prednisolone as the current standard treatment strategy. In addition, we reflect on the challenges of conducting a randomized trial in rare diseases. Trial registration EudraCT 2016-001038-91 . Prospectively registered on 18 April 2016. Graphical Abstract
