Efficacy and Safety of Mycophenolate Mofetil and Tacrolimus as Second-line Therapy for Patients With Autoimmune Hepatitis

Cumali Efe; Hannes Hagström; Henriette Ytting; Rahima A. Bhanji; Niklas F. Müller; Qixia Wang; Tugrul Purnak; Luigi Muratori; Mårten Werner; Hanns Ulrich Marschall; Paolo Muratori; Fulya Gunşar; Daniel Klintman; Albert Parés; Alexandra Heurgué-Berlot; Thomas D. Schiano; Mustafa Cengiz; Michele May-Sien Tana; Xiong Ma; Aldo J. Montano-Loza; Thomas Berg; Sumita Verma; Fin Stolze Larsen; Ersan Ozaslan; Michael A. Heneghan; Eric M. Yoshida; Staffan Wahlin

doi:10.1016/j.cgh.2017.06.001

Efficacy and Safety of Mycophenolate Mofetil and Tacrolimus as Second-line Therapy for Patients With Autoimmune Hepatitis

Cumali Efe, Hannes Hagström, Henriette Ytting, Rahima A. Bhanji, Niklas F. Müller, Qixia Wang, Tugrul Purnak, Luigi Muratori, Mårten Werner, Hanns Ulrich Marschall, Paolo Muratori, Fulya Gunşar, Daniel Klintman, Albert Parés, Alexandra Heurgué-Berlot, Thomas D. Schiano, Mustafa Cengiz, Michele May-Sien Tana, Xiong Ma, Aldo J. Montano-LozaThomas Berg, Sumita Verma, Fin Stolze Larsen, Ersan Ozaslan, Michael A. Heneghan, Eric M. Yoshida, Staffan Wahlin

Research output: Contribution to journal › Article › peer-review

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Abstract

Background & Aims Predniso(lo)ne, alone or in combination with azathioprine, is the standard-of-care (SOC) therapy for autoimmune hepatitis (AIH). However, the SOC therapy is poorly tolerated or does not control disease activity in up to 20% of patients. We assessed the efficacy of mycophenolate mofetil (MMF) and tacrolimus as second-line therapy for patients with AIH. Methods We performed a retrospective study of data (from 19 centers in Europe, the United States, Canada, and China) from 201 patients with AIH who received second-line therapy (121 received MMF and 80 received tacrolimus), for a median of 62 months (range, 6–190 mo). Patients were categorized according to their response to SOC. Patients in group 1 (n = 108) had a complete response to the SOC, but were switched to second-line therapy as a result of side effects of predniso(lo)ne or azathioprine, whereas patients in group 2 (n = 93) had not responded to SOC. Results There was no significant difference in the proportion of patients with a complete response to MMF (69.4%) vs tacrolimus (72.5%) (P =.639). In group 1, MMF and tacrolimus maintained a biochemical remission in 91.9% and 94.1% of patients, respectively (P =.682). Significantly more group 2 patients given tacrolimus compared with MMF had a complete response (56.5% vs 34%, respectively; P =.029) There were similar proportions of liver-related deaths or liver transplantation among patients given MMF (13.2%) vs tacrolimus (10.3%) (log-rank, P =.472). Ten patients receiving MMF (8.3%) and 10 patients receiving tacrolimus (12.5%) developed side effects that required therapy withdrawal. Conclusions Long-term therapy with MMF or tacrolimus generally was well tolerated by patients with AIH. The agents were equally effective in previous complete responders who did not tolerate SOC therapy. Tacrolimus led to a complete response in a greater proportion of previous nonresponder patients compared with MMF.

Original language	English
Pages (from-to)	1950-1956.e1
Journal	Clinical Gastroenterology and Hepatology
Volume	15
Issue number	12
DOIs	https://doi.org/10.1016/j.cgh.2017.06.001
State	Published - Dec 2017

Keywords

Autoimmune Liver Disease
Liver Failure
Liver Transplantation
Simplified Criteria

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10.1016/j.cgh.2017.06.001

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Efe, C., Hagström, H., Ytting, H., Bhanji, R. A., Müller, N. F., Wang, Q., Purnak, T., Muratori, L., Werner, M., Marschall, H. U., Muratori, P., Gunşar, F., Klintman, D., Parés, A., Heurgué-Berlot, A., Schiano, T. D., Cengiz, M., May-Sien Tana, M., Ma, X., ... Wahlin, S. (2017). Efficacy and Safety of Mycophenolate Mofetil and Tacrolimus as Second-line Therapy for Patients With Autoimmune Hepatitis. Clinical Gastroenterology and Hepatology, 15(12), 1950-1956.e1. https://doi.org/10.1016/j.cgh.2017.06.001

@article{b262229b660a4e9fb51cd60cb2203482,

title = "Efficacy and Safety of Mycophenolate Mofetil and Tacrolimus as Second-line Therapy for Patients With Autoimmune Hepatitis",

abstract = "Background & Aims Predniso(lo)ne, alone or in combination with azathioprine, is the standard-of-care (SOC) therapy for autoimmune hepatitis (AIH). However, the SOC therapy is poorly tolerated or does not control disease activity in up to 20% of patients. We assessed the efficacy of mycophenolate mofetil (MMF) and tacrolimus as second-line therapy for patients with AIH. Methods We performed a retrospective study of data (from 19 centers in Europe, the United States, Canada, and China) from 201 patients with AIH who received second-line therapy (121 received MMF and 80 received tacrolimus), for a median of 62 months (range, 6–190 mo). Patients were categorized according to their response to SOC. Patients in group 1 (n = 108) had a complete response to the SOC, but were switched to second-line therapy as a result of side effects of predniso(lo)ne or azathioprine, whereas patients in group 2 (n = 93) had not responded to SOC. Results There was no significant difference in the proportion of patients with a complete response to MMF (69.4%) vs tacrolimus (72.5%) (P =.639). In group 1, MMF and tacrolimus maintained a biochemical remission in 91.9% and 94.1% of patients, respectively (P =.682). Significantly more group 2 patients given tacrolimus compared with MMF had a complete response (56.5% vs 34%, respectively; P =.029) There were similar proportions of liver-related deaths or liver transplantation among patients given MMF (13.2%) vs tacrolimus (10.3%) (log-rank, P =.472). Ten patients receiving MMF (8.3%) and 10 patients receiving tacrolimus (12.5%) developed side effects that required therapy withdrawal. Conclusions Long-term therapy with MMF or tacrolimus generally was well tolerated by patients with AIH. The agents were equally effective in previous complete responders who did not tolerate SOC therapy. Tacrolimus led to a complete response in a greater proportion of previous nonresponder patients compared with MMF.",

keywords = "Autoimmune Liver Disease, Liver Failure, Liver Transplantation, Simplified Criteria",

author = "Cumali Efe and Hannes Hagstr{\"o}m and Henriette Ytting and Bhanji, {Rahima A.} and M{\"u}ller, {Niklas F.} and Qixia Wang and Tugrul Purnak and Luigi Muratori and M{\aa}rten Werner and Marschall, {Hanns Ulrich} and Paolo Muratori and Fulya Gun{\c s}ar and Daniel Klintman and Albert Par{\'e}s and Alexandra Heurgu{\'e}-Berlot and Schiano, {Thomas D.} and Mustafa Cengiz and {May-Sien Tana}, Michele and Xiong Ma and Montano-Loza, {Aldo J.} and Thomas Berg and Sumita Verma and Larsen, {Fin Stolze} and Ersan Ozaslan and Heneghan, {Michael A.} and Yoshida, {Eric M.} and Staffan Wahlin",

note = "Publisher Copyright: {\textcopyright} 2017 AGA Institute",

year = "2017",

month = dec,

doi = "10.1016/j.cgh.2017.06.001",

language = "English",

volume = "15",

pages = "1950--1956.e1",

journal = "Clinical Gastroenterology and Hepatology",

issn = "1542-3565",

publisher = "W.B. Saunders Ltd",

number = "12",

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Efe, C, Hagström, H, Ytting, H, Bhanji, RA, Müller, NF, Wang, Q, Purnak, T, Muratori, L, Werner, M, Marschall, HU, Muratori, P, Gunşar, F, Klintman, D, Parés, A, Heurgué-Berlot, A, Schiano, TD, Cengiz, M, May-Sien Tana, M, Ma, X, Montano-Loza, AJ, Berg, T, Verma, S, Larsen, FS, Ozaslan, E, Heneghan, MA, Yoshida, EM & Wahlin, S 2017, 'Efficacy and Safety of Mycophenolate Mofetil and Tacrolimus as Second-line Therapy for Patients With Autoimmune Hepatitis', Clinical Gastroenterology and Hepatology, vol. 15, no. 12, pp. 1950-1956.e1. https://doi.org/10.1016/j.cgh.2017.06.001

TY - JOUR

T1 - Efficacy and Safety of Mycophenolate Mofetil and Tacrolimus as Second-line Therapy for Patients With Autoimmune Hepatitis

AU - Efe, Cumali

AU - Hagström, Hannes

AU - Ytting, Henriette

AU - Bhanji, Rahima A.

AU - Müller, Niklas F.

AU - Wang, Qixia

AU - Purnak, Tugrul

AU - Muratori, Luigi

AU - Werner, Mårten

AU - Marschall, Hanns Ulrich

AU - Muratori, Paolo

AU - Gunşar, Fulya

AU - Klintman, Daniel

AU - Parés, Albert

AU - Heurgué-Berlot, Alexandra

AU - Schiano, Thomas D.

AU - Cengiz, Mustafa

AU - May-Sien Tana, Michele

AU - Ma, Xiong

AU - Montano-Loza, Aldo J.

AU - Berg, Thomas

AU - Verma, Sumita

AU - Larsen, Fin Stolze

AU - Ozaslan, Ersan

AU - Heneghan, Michael A.

AU - Yoshida, Eric M.

AU - Wahlin, Staffan

PY - 2017/12

Y1 - 2017/12

N2 - Background & Aims Predniso(lo)ne, alone or in combination with azathioprine, is the standard-of-care (SOC) therapy for autoimmune hepatitis (AIH). However, the SOC therapy is poorly tolerated or does not control disease activity in up to 20% of patients. We assessed the efficacy of mycophenolate mofetil (MMF) and tacrolimus as second-line therapy for patients with AIH. Methods We performed a retrospective study of data (from 19 centers in Europe, the United States, Canada, and China) from 201 patients with AIH who received second-line therapy (121 received MMF and 80 received tacrolimus), for a median of 62 months (range, 6–190 mo). Patients were categorized according to their response to SOC. Patients in group 1 (n = 108) had a complete response to the SOC, but were switched to second-line therapy as a result of side effects of predniso(lo)ne or azathioprine, whereas patients in group 2 (n = 93) had not responded to SOC. Results There was no significant difference in the proportion of patients with a complete response to MMF (69.4%) vs tacrolimus (72.5%) (P =.639). In group 1, MMF and tacrolimus maintained a biochemical remission in 91.9% and 94.1% of patients, respectively (P =.682). Significantly more group 2 patients given tacrolimus compared with MMF had a complete response (56.5% vs 34%, respectively; P =.029) There were similar proportions of liver-related deaths or liver transplantation among patients given MMF (13.2%) vs tacrolimus (10.3%) (log-rank, P =.472). Ten patients receiving MMF (8.3%) and 10 patients receiving tacrolimus (12.5%) developed side effects that required therapy withdrawal. Conclusions Long-term therapy with MMF or tacrolimus generally was well tolerated by patients with AIH. The agents were equally effective in previous complete responders who did not tolerate SOC therapy. Tacrolimus led to a complete response in a greater proportion of previous nonresponder patients compared with MMF.

AB - Background & Aims Predniso(lo)ne, alone or in combination with azathioprine, is the standard-of-care (SOC) therapy for autoimmune hepatitis (AIH). However, the SOC therapy is poorly tolerated or does not control disease activity in up to 20% of patients. We assessed the efficacy of mycophenolate mofetil (MMF) and tacrolimus as second-line therapy for patients with AIH. Methods We performed a retrospective study of data (from 19 centers in Europe, the United States, Canada, and China) from 201 patients with AIH who received second-line therapy (121 received MMF and 80 received tacrolimus), for a median of 62 months (range, 6–190 mo). Patients were categorized according to their response to SOC. Patients in group 1 (n = 108) had a complete response to the SOC, but were switched to second-line therapy as a result of side effects of predniso(lo)ne or azathioprine, whereas patients in group 2 (n = 93) had not responded to SOC. Results There was no significant difference in the proportion of patients with a complete response to MMF (69.4%) vs tacrolimus (72.5%) (P =.639). In group 1, MMF and tacrolimus maintained a biochemical remission in 91.9% and 94.1% of patients, respectively (P =.682). Significantly more group 2 patients given tacrolimus compared with MMF had a complete response (56.5% vs 34%, respectively; P =.029) There were similar proportions of liver-related deaths or liver transplantation among patients given MMF (13.2%) vs tacrolimus (10.3%) (log-rank, P =.472). Ten patients receiving MMF (8.3%) and 10 patients receiving tacrolimus (12.5%) developed side effects that required therapy withdrawal. Conclusions Long-term therapy with MMF or tacrolimus generally was well tolerated by patients with AIH. The agents were equally effective in previous complete responders who did not tolerate SOC therapy. Tacrolimus led to a complete response in a greater proportion of previous nonresponder patients compared with MMF.

KW - Autoimmune Liver Disease

KW - Liver Failure

KW - Liver Transplantation

KW - Simplified Criteria

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U2 - 10.1016/j.cgh.2017.06.001

DO - 10.1016/j.cgh.2017.06.001

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AN - SCOPUS:85029848036

SN - 1542-3565

VL - 15

SP - 1950-1956.e1

JO - Clinical Gastroenterology and Hepatology

JF - Clinical Gastroenterology and Hepatology

IS - 12

ER -

Efficacy and Safety of Mycophenolate Mofetil and Tacrolimus as Second-line Therapy for Patients With Autoimmune Hepatitis

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