TY - JOUR
T1 - Tacrolimus versus mycophenolate for AutoImmune hepatitis patients with incompLete response On first-line therapy (TAILOR study)
T2 - a study protocol for a phase III, open-label, multicentre, randomised controlled trial
AU - Stoelinga, Anna E. C.
AU - Tushuizen, Maarten E.
AU - van den Hout, Wilbert B.
AU - Girondo, Mar D. M. Rodriguez
AU - de Vries, Elsemieke S.
AU - Levens, Amar D.
AU - Moes, Dirk-Jan A. R.
AU - Gevers, Tom J. G.
AU - van der Meer, Suzanne
AU - Brouwer, Hans T.
AU - de Jonge, Hendrik J. M.
AU - de Boer, Ynte S.
AU - Beuers, Ulrich H. W.
AU - van der Meer, Adriaan J.
AU - van den Berg, Aad P.
AU - Guichelaar, Maureen M. J.
AU - Drenth, Joost P. H.
AU - van Hoek, Bart
AU - Dutch Autoimmune Hepatitis Group
PY - 2024/1/17
Y1 - 2024/1/17
N2 - BackgroundAutoimmune hepatitis (AIH) is a rare, chronic inflammatory disease of the liver. The treatment goal is reaching complete biochemical response (CR), defined as the normalisation of aspartate and alanine aminotransferases and immunoglobulin gamma. Ongoing AIH activity can lead to fibrosis and (decompensated) cirrhosis. Incomplete biochemical response is the most important risk factor for liver transplantation or liver-related mortality. First-line treatment consists of a combination of azathioprine and prednisolone. If CR is not reached, tacrolimus (TAC) or mycophenolate mofetil (MMF) can be used as second-line therapy. Both products are registered for the prevention of graft rejection in solid organ transplant recipients. The aim of this study is to compare the effectiveness and safety of TAC and MMF as second-line treatment for AIH.MethodsThe TAILOR study is a phase IIIB, multicentre, open-label, parallel-group, randomised (1:1) controlled trial performed in large teaching and university hospitals in the Netherlands. We will enrol 86 patients with AIH who have not reached CR after at least 6 months of treatment with first-line therapy. Patients are randomised to TAC (0.07 mg/kg/day initially and adjusted by trough levels) or MMF (max 2000 mg/day), stratified by the presence of cirrhosis at inclusion. The primary endpoint is the difference in the proportion of patients reaching CR after 12 months. Secondary endpoints include the difference in the proportion of patients reaching CR after 6 months, adverse effects, difference in fibrogenesis, quality of life and cost-effectiveness.DiscussionThis is the first randomised controlled trial comparing two second-line therapies for AIH. Currently, second-line treatment is based on retrospective cohort studies. The rarity of AIH is the main issue in clinical research for alternative treatment options. The results of this trial can be implemented in existing international clinical guidelines.Trial registrationClinicalTrials.gov NCT05221411. Retrospectively registered on 3 February 2022; EudraCT number 2021-003420-33. Prospectively registered on 16 June 2021.
AB - BackgroundAutoimmune hepatitis (AIH) is a rare, chronic inflammatory disease of the liver. The treatment goal is reaching complete biochemical response (CR), defined as the normalisation of aspartate and alanine aminotransferases and immunoglobulin gamma. Ongoing AIH activity can lead to fibrosis and (decompensated) cirrhosis. Incomplete biochemical response is the most important risk factor for liver transplantation or liver-related mortality. First-line treatment consists of a combination of azathioprine and prednisolone. If CR is not reached, tacrolimus (TAC) or mycophenolate mofetil (MMF) can be used as second-line therapy. Both products are registered for the prevention of graft rejection in solid organ transplant recipients. The aim of this study is to compare the effectiveness and safety of TAC and MMF as second-line treatment for AIH.MethodsThe TAILOR study is a phase IIIB, multicentre, open-label, parallel-group, randomised (1:1) controlled trial performed in large teaching and university hospitals in the Netherlands. We will enrol 86 patients with AIH who have not reached CR after at least 6 months of treatment with first-line therapy. Patients are randomised to TAC (0.07 mg/kg/day initially and adjusted by trough levels) or MMF (max 2000 mg/day), stratified by the presence of cirrhosis at inclusion. The primary endpoint is the difference in the proportion of patients reaching CR after 12 months. Secondary endpoints include the difference in the proportion of patients reaching CR after 6 months, adverse effects, difference in fibrogenesis, quality of life and cost-effectiveness.DiscussionThis is the first randomised controlled trial comparing two second-line therapies for AIH. Currently, second-line treatment is based on retrospective cohort studies. The rarity of AIH is the main issue in clinical research for alternative treatment options. The results of this trial can be implemented in existing international clinical guidelines.Trial registrationClinicalTrials.gov NCT05221411. Retrospectively registered on 3 February 2022; EudraCT number 2021-003420-33. Prospectively registered on 16 June 2021.
KW - AIH
KW - Autoimmune hepatitis
KW - Autoimmune liver disease
KW - Tacrolimus
KW - Mycophenolate mofetil
KW - Randomised controlled trials
KW - Second-line treatment
KW - Complete biochemical response
KW - TRANSIENT ELASTOGRAPHY
KW - BIOCHEMICAL REMISSION
KW - MOFETIL
KW - FIBROSIS
KW - EFFICACY
KW - CRITERIA
KW - KIDNEY
KW - INDUCTION
KW - DIAGNOSIS
KW - 2ND-LINE
U2 - 10.1186/s13063-023-07832-w
DO - 10.1186/s13063-023-07832-w
M3 - Article
SN - 1745-6215
VL - 25
JO - Trials
JF - Trials
IS - 1
M1 - 61
ER -