Efficacy and Safety of Mycophenolate Mofetil in Patients With Autoimmune Hepatitis and Suboptimal Outcomes After Standard Therapy

Stuart K. Roberts, Ricky Lim, Simone Strasser, Amanda Nicoll, Alessia Gazzola, Joanne Mitchell, Way Siow, Tiffany Khoo, Zaki Hamarneh, Martin Weltman, Paul Gow, Natasha Janko, Edmund Tse, Gauri Mishra, En Hsiang Cheng, Miriam Levy, Wendy Cheng, Siddharth Sood, Richard Skoien, Jonathan Mitchell & 8 others Amany Zekry, Jacob George, Gerry MacQuillan, Alan Wigg, Katherine Stuart, William Sievert, Geoffrey McCaughan, ALA Clinical Research Network

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Background & Aims: Little is known about outcomes of patients with autoimmune hepatitis (AIH) who have a suboptimal outcome to standard therapy and are then given mycophenolate mofetil as rescue therapy. We evaluated the efficacy and safety of mycophenolate mofetil in patients failed by or intolerant to corticosteroids, with or without azathioprine. Methods: We performed a retrospective study of 105 patients with AIH who received mycophenolate mofetil therapy after an inadequate response or intolerance to standard therapy (98% received combination therapy with corticosteroids plus thiopurines). Patients were recruited from 17 liver clinics via the Australian Liver Association Clinical Research Network. We reviewed records for baseline demographic features and characteristics of liver disease, initial therapy, mycophenolate mofetil indications, treatment outcome, and side effects. The primary outcome was biochemical remission, defined as levels of alanine and aspartate transferase and IgG level within the normal reference range, with or without normal liver histology within the first 2 years of treatment. Results: The indication for mycophenolate mofetil therapy was non-response to treatment for 40% of cases and intolerance to therapy for 60%. Overall, 63 patients (60%) achieved biochemical remission following a median 12 weeks treatment with mycophenolate mofetil. The proportion of patients who achieved biochemical remission was similar between patients receiving mycophenolate mofetil for non-response to standard therapy (57%) and patients with intolerance to standard therapy (62%). However, a lower proportion of patients with cirrhosis achieved biochemical remission (47%) than patients without cirrhosis (6%) (P =.07). Serious adverse events occurred in 3 patients (2.7%) including 1 death, and 10 patients (9.2%) discontinued mycophenolate mofetil because of adverse events. Conclusion: In this retrospective study of patients with AIH who received mycophenolate mofetil as a rescue therapy, we found the drug to be well tolerated and moderately effective, inducing biochemical remission in 60% of subjects. Rates of response are lower and rates of infection are higher in patients with AIH and cirrhosis. Prospective studies of mycophenolate mofetil are warranted for this population.

Original languageEnglish
Pages (from-to)268-277
Number of pages10
JournalClinical Gastroenterology and Hepatology
Volume16
Issue number2
DOIs
Publication statusPublished - 1 Feb 2018

Keywords

  • Immune Suppressant
  • Inflammation
  • Periportal Hepatitis
  • TAPESTRY Study

Cite this

Roberts, Stuart K. ; Lim, Ricky ; Strasser, Simone ; Nicoll, Amanda ; Gazzola, Alessia ; Mitchell, Joanne ; Siow, Way ; Khoo, Tiffany ; Hamarneh, Zaki ; Weltman, Martin ; Gow, Paul ; Janko, Natasha ; Tse, Edmund ; Mishra, Gauri ; Cheng, En Hsiang ; Levy, Miriam ; Cheng, Wendy ; Sood, Siddharth ; Skoien, Richard ; Mitchell, Jonathan ; Zekry, Amany ; George, Jacob ; MacQuillan, Gerry ; Wigg, Alan ; Stuart, Katherine ; Sievert, William ; McCaughan, Geoffrey ; ALA Clinical Research Network. / Efficacy and Safety of Mycophenolate Mofetil in Patients With Autoimmune Hepatitis and Suboptimal Outcomes After Standard Therapy. In: Clinical Gastroenterology and Hepatology. 2018 ; Vol. 16, No. 2. pp. 268-277.
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title = "Efficacy and Safety of Mycophenolate Mofetil in Patients With Autoimmune Hepatitis and Suboptimal Outcomes After Standard Therapy",
abstract = "Background & Aims: Little is known about outcomes of patients with autoimmune hepatitis (AIH) who have a suboptimal outcome to standard therapy and are then given mycophenolate mofetil as rescue therapy. We evaluated the efficacy and safety of mycophenolate mofetil in patients failed by or intolerant to corticosteroids, with or without azathioprine. Methods: We performed a retrospective study of 105 patients with AIH who received mycophenolate mofetil therapy after an inadequate response or intolerance to standard therapy (98{\%} received combination therapy with corticosteroids plus thiopurines). Patients were recruited from 17 liver clinics via the Australian Liver Association Clinical Research Network. We reviewed records for baseline demographic features and characteristics of liver disease, initial therapy, mycophenolate mofetil indications, treatment outcome, and side effects. The primary outcome was biochemical remission, defined as levels of alanine and aspartate transferase and IgG level within the normal reference range, with or without normal liver histology within the first 2 years of treatment. Results: The indication for mycophenolate mofetil therapy was non-response to treatment for 40{\%} of cases and intolerance to therapy for 60{\%}. Overall, 63 patients (60{\%}) achieved biochemical remission following a median 12 weeks treatment with mycophenolate mofetil. The proportion of patients who achieved biochemical remission was similar between patients receiving mycophenolate mofetil for non-response to standard therapy (57{\%}) and patients with intolerance to standard therapy (62{\%}). However, a lower proportion of patients with cirrhosis achieved biochemical remission (47{\%}) than patients without cirrhosis (6{\%}) (P =.07). Serious adverse events occurred in 3 patients (2.7{\%}) including 1 death, and 10 patients (9.2{\%}) discontinued mycophenolate mofetil because of adverse events. Conclusion: In this retrospective study of patients with AIH who received mycophenolate mofetil as a rescue therapy, we found the drug to be well tolerated and moderately effective, inducing biochemical remission in 60{\%} of subjects. Rates of response are lower and rates of infection are higher in patients with AIH and cirrhosis. Prospective studies of mycophenolate mofetil are warranted for this population.",
keywords = "Immune Suppressant, Inflammation, Periportal Hepatitis, TAPESTRY Study",
author = "Roberts, {Stuart K.} and Ricky Lim and Simone Strasser and Amanda Nicoll and Alessia Gazzola and Joanne Mitchell and Way Siow and Tiffany Khoo and Zaki Hamarneh and Martin Weltman and Paul Gow and Natasha Janko and Edmund Tse and Gauri Mishra and Cheng, {En Hsiang} and Miriam Levy and Wendy Cheng and Siddharth Sood and Richard Skoien and Jonathan Mitchell and Amany Zekry and Jacob George and Gerry MacQuillan and Alan Wigg and Katherine Stuart and William Sievert and Geoffrey McCaughan and {ALA Clinical Research Network}",
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pages = "268--277",
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Roberts, SK, Lim, R, Strasser, S, Nicoll, A, Gazzola, A, Mitchell, J, Siow, W, Khoo, T, Hamarneh, Z, Weltman, M, Gow, P, Janko, N, Tse, E, Mishra, G, Cheng, EH, Levy, M, Cheng, W, Sood, S, Skoien, R, Mitchell, J, Zekry, A, George, J, MacQuillan, G, Wigg, A, Stuart, K, Sievert, W, McCaughan, G & ALA Clinical Research Network 2018, 'Efficacy and Safety of Mycophenolate Mofetil in Patients With Autoimmune Hepatitis and Suboptimal Outcomes After Standard Therapy', Clinical Gastroenterology and Hepatology, vol. 16, no. 2, pp. 268-277. https://doi.org/10.1016/j.cgh.2017.09.063

Efficacy and Safety of Mycophenolate Mofetil in Patients With Autoimmune Hepatitis and Suboptimal Outcomes After Standard Therapy. / Roberts, Stuart K.; Lim, Ricky; Strasser, Simone; Nicoll, Amanda; Gazzola, Alessia; Mitchell, Joanne; Siow, Way; Khoo, Tiffany; Hamarneh, Zaki; Weltman, Martin; Gow, Paul; Janko, Natasha; Tse, Edmund; Mishra, Gauri; Cheng, En Hsiang; Levy, Miriam; Cheng, Wendy; Sood, Siddharth; Skoien, Richard; Mitchell, Jonathan; Zekry, Amany; George, Jacob; MacQuillan, Gerry; Wigg, Alan; Stuart, Katherine; Sievert, William; McCaughan, Geoffrey; ALA Clinical Research Network.

In: Clinical Gastroenterology and Hepatology, Vol. 16, No. 2, 01.02.2018, p. 268-277.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Efficacy and Safety of Mycophenolate Mofetil in Patients With Autoimmune Hepatitis and Suboptimal Outcomes After Standard Therapy

AU - Roberts, Stuart K.

AU - Lim, Ricky

AU - Strasser, Simone

AU - Nicoll, Amanda

AU - Gazzola, Alessia

AU - Mitchell, Joanne

AU - Siow, Way

AU - Khoo, Tiffany

AU - Hamarneh, Zaki

AU - Weltman, Martin

AU - Gow, Paul

AU - Janko, Natasha

AU - Tse, Edmund

AU - Mishra, Gauri

AU - Cheng, En Hsiang

AU - Levy, Miriam

AU - Cheng, Wendy

AU - Sood, Siddharth

AU - Skoien, Richard

AU - Mitchell, Jonathan

AU - Zekry, Amany

AU - George, Jacob

AU - MacQuillan, Gerry

AU - Wigg, Alan

AU - Stuart, Katherine

AU - Sievert, William

AU - McCaughan, Geoffrey

AU - ALA Clinical Research Network

PY - 2018/2/1

Y1 - 2018/2/1

N2 - Background & Aims: Little is known about outcomes of patients with autoimmune hepatitis (AIH) who have a suboptimal outcome to standard therapy and are then given mycophenolate mofetil as rescue therapy. We evaluated the efficacy and safety of mycophenolate mofetil in patients failed by or intolerant to corticosteroids, with or without azathioprine. Methods: We performed a retrospective study of 105 patients with AIH who received mycophenolate mofetil therapy after an inadequate response or intolerance to standard therapy (98% received combination therapy with corticosteroids plus thiopurines). Patients were recruited from 17 liver clinics via the Australian Liver Association Clinical Research Network. We reviewed records for baseline demographic features and characteristics of liver disease, initial therapy, mycophenolate mofetil indications, treatment outcome, and side effects. The primary outcome was biochemical remission, defined as levels of alanine and aspartate transferase and IgG level within the normal reference range, with or without normal liver histology within the first 2 years of treatment. Results: The indication for mycophenolate mofetil therapy was non-response to treatment for 40% of cases and intolerance to therapy for 60%. Overall, 63 patients (60%) achieved biochemical remission following a median 12 weeks treatment with mycophenolate mofetil. The proportion of patients who achieved biochemical remission was similar between patients receiving mycophenolate mofetil for non-response to standard therapy (57%) and patients with intolerance to standard therapy (62%). However, a lower proportion of patients with cirrhosis achieved biochemical remission (47%) than patients without cirrhosis (6%) (P =.07). Serious adverse events occurred in 3 patients (2.7%) including 1 death, and 10 patients (9.2%) discontinued mycophenolate mofetil because of adverse events. Conclusion: In this retrospective study of patients with AIH who received mycophenolate mofetil as a rescue therapy, we found the drug to be well tolerated and moderately effective, inducing biochemical remission in 60% of subjects. Rates of response are lower and rates of infection are higher in patients with AIH and cirrhosis. Prospective studies of mycophenolate mofetil are warranted for this population.

AB - Background & Aims: Little is known about outcomes of patients with autoimmune hepatitis (AIH) who have a suboptimal outcome to standard therapy and are then given mycophenolate mofetil as rescue therapy. We evaluated the efficacy and safety of mycophenolate mofetil in patients failed by or intolerant to corticosteroids, with or without azathioprine. Methods: We performed a retrospective study of 105 patients with AIH who received mycophenolate mofetil therapy after an inadequate response or intolerance to standard therapy (98% received combination therapy with corticosteroids plus thiopurines). Patients were recruited from 17 liver clinics via the Australian Liver Association Clinical Research Network. We reviewed records for baseline demographic features and characteristics of liver disease, initial therapy, mycophenolate mofetil indications, treatment outcome, and side effects. The primary outcome was biochemical remission, defined as levels of alanine and aspartate transferase and IgG level within the normal reference range, with or without normal liver histology within the first 2 years of treatment. Results: The indication for mycophenolate mofetil therapy was non-response to treatment for 40% of cases and intolerance to therapy for 60%. Overall, 63 patients (60%) achieved biochemical remission following a median 12 weeks treatment with mycophenolate mofetil. The proportion of patients who achieved biochemical remission was similar between patients receiving mycophenolate mofetil for non-response to standard therapy (57%) and patients with intolerance to standard therapy (62%). However, a lower proportion of patients with cirrhosis achieved biochemical remission (47%) than patients without cirrhosis (6%) (P =.07). Serious adverse events occurred in 3 patients (2.7%) including 1 death, and 10 patients (9.2%) discontinued mycophenolate mofetil because of adverse events. Conclusion: In this retrospective study of patients with AIH who received mycophenolate mofetil as a rescue therapy, we found the drug to be well tolerated and moderately effective, inducing biochemical remission in 60% of subjects. Rates of response are lower and rates of infection are higher in patients with AIH and cirrhosis. Prospective studies of mycophenolate mofetil are warranted for this population.

KW - Immune Suppressant

KW - Inflammation

KW - Periportal Hepatitis

KW - TAPESTRY Study

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DO - 10.1016/j.cgh.2017.09.063

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EP - 277

JO - Clinical Gastroenterology and Hepatology

JF - Clinical Gastroenterology and Hepatology

SN - 1542-3565

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