TY - JOUR
T1 - Assessing the efficacy and safety of mycophenolate mofetil versus azathioprine in patients with autoimmune hepatitis (CAMARO trial)
T2 - study protocol for a randomised controlled trial
AU - Snijders, Romée J A L M
AU - Stoelinga, Anna E C
AU - Gevers, Tom J G
AU - Pape, Simon
AU - Biewenga, Maaike
AU - Verdonk, Robert C
AU - de Jonge, Hendrik J M
AU - Vrolijk, Jan Maarten
AU - Bakker, Sjoerd F
AU - Vanwolleghem, Thomas
AU - de Boer, Ynto S
AU - Pronk, Martine A M C Baven
AU - Beuers, Ulrich H W
AU - van der Meer, Adriaan J
AU - van Gerven, Nicole M F
AU - Sijtsma, Marijn G M
AU - Verwer, Bart J
AU - Gisbertz, Ingrid A M
AU - Bartelink, Maartje
AU - van den Brand, Floris F
AU - Sebib Korkmaz, Kerem
AU - van den Berg, Aad P
AU - Guichelaar, Maureen M J
AU - Soufidi, Khalida
AU - Levens, Amar D
AU - van Hoek, Bart
AU - Drenth, Joost P H
AU - Dutch Autoimmune Hepatitis Working Group
N1 - © 2022. The Author(s).
PY - 2022/12/13
Y1 - 2022/12/13
N2 - 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.
AB - 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.
KW - Adult
KW - Humans
KW - Mycophenolic Acid/adverse effects
KW - Azathioprine/adverse effects
KW - Hepatitis, Autoimmune/diagnosis
KW - Quality of Life
KW - End Stage Liver Disease
KW - Immunosuppressive Agents/adverse effects
KW - Treatment Outcome
KW - Severity of Illness Index
KW - Prednisolone/adverse effects
KW - Randomized Controlled Trials as Topic
KW - Multicenter Studies as Topic
U2 - 10.1186/s13063-022-06890-w
DO - 10.1186/s13063-022-06890-w
M3 - Article
C2 - 36514163
SN - 1745-6215
VL - 23
SP - 1012
JO - Trials
JF - Trials
IS - 1
ER -