Beneficial response to mycophenolate mofetil by patients with autoimmune hepatitis who have failed standard therapy, is predicted by older age and lower immunoglobulin G and INR levels

Amanda J. Nicoll, Stuart K. Roberts, Ricky Lim, Joanne Mitchell, Martin Weltman, Jacob George, Alan Wigg, Katherine Stuart, Paul Gow, Gerry MacQuillan, Edmund Tse, Miriam Levy, Siddharth Sood, Amany Zekry, Wendy Cheng, Jonathan Mitchell, Richard Skoien, William Sievert, Simone I. Strasser, Geoffrey W. McCaughan & 1 others on behalf of the ALA Clinical Research Network, Gastroenterological Society of Australia

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Background: Mycophenolate mofetil is a commonly used salvage therapy for patients with autoimmune hepatitis (AIH). Aim: To evaluate the predictors of response to mycophenolate rescue therapy to facilitate clinical decision making. Methods: We performed a retrospective observational cohort study of AIH patients managed in 17 major Australian liver centres who received mycophenolate after an inadequate response or intolerance to corticosteroids with/without thiopurine(s). Baseline demographic, clinical and laboratory variables were compared between responders and nonresponders. A multivariable logistic regression model was developed using forward selection to identify independent predictors of treatment response. Results: A total of 105 patients received mycophenolate rescue therapy of whom 63 (60%) achieved biochemical remission. On univariable analysis, older age (P = 0.003), INR < 1.1 (P = 0.02), and lower immunoglobulin gamma (IgG; P < 0.002) levels were associated with treatment response, while no association was found with cirrhosis status (P = 0.07) or treatment indication (P = 0.63). On multivariable analysis, lower pre-treatment serum IgG level (P = 0.01), higher age at commencing mycophenolate (P = 0.01) and higher INR (P = 0.03) were the only significant independent predictors. An IgG level <17 g/L had a positive and negative predictive value for response of 71% and 60% respectively, while age ≥54 years when commencing mycophenolate had a positive and negative predictive value for response of 80% and 59% respectively. Conclusion: Mycophenolate remains an excellent treatment option for patients with AIH refractory to or intolerant of standard therapy with those most likely to benefit being older and/or having lower pre-treatment IgG levels.

Original languageEnglish
Pages (from-to)1314-1322
Number of pages9
JournalAlimentary Pharmacology and Therapeutics
Volume49
Issue number10
DOIs
Publication statusPublished - 1 May 2019

Cite this

Nicoll, Amanda J. ; Roberts, Stuart K. ; Lim, Ricky ; Mitchell, Joanne ; Weltman, Martin ; George, Jacob ; Wigg, Alan ; Stuart, Katherine ; Gow, Paul ; MacQuillan, Gerry ; Tse, Edmund ; Levy, Miriam ; Sood, Siddharth ; Zekry, Amany ; Cheng, Wendy ; Mitchell, Jonathan ; Skoien, Richard ; Sievert, William ; Strasser, Simone I. ; McCaughan, Geoffrey W. ; on behalf of the ALA Clinical Research Network, Gastroenterological Society of Australia. / Beneficial response to mycophenolate mofetil by patients with autoimmune hepatitis who have failed standard therapy, is predicted by older age and lower immunoglobulin G and INR levels. In: Alimentary Pharmacology and Therapeutics. 2019 ; Vol. 49, No. 10. pp. 1314-1322.
@article{ba62bfd61e8547efbf858a1394231834,
title = "Beneficial response to mycophenolate mofetil by patients with autoimmune hepatitis who have failed standard therapy, is predicted by older age and lower immunoglobulin G and INR levels",
abstract = "Background: Mycophenolate mofetil is a commonly used salvage therapy for patients with autoimmune hepatitis (AIH). Aim: To evaluate the predictors of response to mycophenolate rescue therapy to facilitate clinical decision making. Methods: We performed a retrospective observational cohort study of AIH patients managed in 17 major Australian liver centres who received mycophenolate after an inadequate response or intolerance to corticosteroids with/without thiopurine(s). Baseline demographic, clinical and laboratory variables were compared between responders and nonresponders. A multivariable logistic regression model was developed using forward selection to identify independent predictors of treatment response. Results: A total of 105 patients received mycophenolate rescue therapy of whom 63 (60{\%}) achieved biochemical remission. On univariable analysis, older age (P = 0.003), INR < 1.1 (P = 0.02), and lower immunoglobulin gamma (IgG; P < 0.002) levels were associated with treatment response, while no association was found with cirrhosis status (P = 0.07) or treatment indication (P = 0.63). On multivariable analysis, lower pre-treatment serum IgG level (P = 0.01), higher age at commencing mycophenolate (P = 0.01) and higher INR (P = 0.03) were the only significant independent predictors. An IgG level <17 g/L had a positive and negative predictive value for response of 71{\%} and 60{\%} respectively, while age ≥54 years when commencing mycophenolate had a positive and negative predictive value for response of 80{\%} and 59{\%} respectively. Conclusion: Mycophenolate remains an excellent treatment option for patients with AIH refractory to or intolerant of standard therapy with those most likely to benefit being older and/or having lower pre-treatment IgG levels.",
author = "Nicoll, {Amanda J.} and Roberts, {Stuart K.} and Ricky Lim and Joanne Mitchell and Martin Weltman and Jacob George and Alan Wigg and Katherine Stuart and Paul Gow and Gerry MacQuillan and Edmund Tse and Miriam Levy and Siddharth Sood and Amany Zekry and Wendy Cheng and Jonathan Mitchell and Richard Skoien and William Sievert and Strasser, {Simone I.} and McCaughan, {Geoffrey W.} and {on behalf of the ALA Clinical Research Network, Gastroenterological Society of Australia}",
year = "2019",
month = "5",
day = "1",
doi = "10.1111/apt.15248",
language = "English",
volume = "49",
pages = "1314--1322",
journal = "Alimentary Pharmacology and Therapeutics",
issn = "0269-2813",
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Nicoll, AJ, Roberts, SK, Lim, R, Mitchell, J, Weltman, M, George, J, Wigg, A, Stuart, K, Gow, P, MacQuillan, G, Tse, E, Levy, M, Sood, S, Zekry, A, Cheng, W, Mitchell, J, Skoien, R, Sievert, W, Strasser, SI, McCaughan, GW & on behalf of the ALA Clinical Research Network, Gastroenterological Society of Australia 2019, 'Beneficial response to mycophenolate mofetil by patients with autoimmune hepatitis who have failed standard therapy, is predicted by older age and lower immunoglobulin G and INR levels' Alimentary Pharmacology and Therapeutics, vol. 49, no. 10, pp. 1314-1322. https://doi.org/10.1111/apt.15248

Beneficial response to mycophenolate mofetil by patients with autoimmune hepatitis who have failed standard therapy, is predicted by older age and lower immunoglobulin G and INR levels. / Nicoll, Amanda J.; Roberts, Stuart K.; Lim, Ricky; Mitchell, Joanne; Weltman, Martin; George, Jacob; Wigg, Alan; Stuart, Katherine; Gow, Paul; MacQuillan, Gerry; Tse, Edmund; Levy, Miriam; Sood, Siddharth; Zekry, Amany; Cheng, Wendy; Mitchell, Jonathan; Skoien, Richard; Sievert, William; Strasser, Simone I.; McCaughan, Geoffrey W.; on behalf of the ALA Clinical Research Network, Gastroenterological Society of Australia.

In: Alimentary Pharmacology and Therapeutics, Vol. 49, No. 10, 01.05.2019, p. 1314-1322.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Beneficial response to mycophenolate mofetil by patients with autoimmune hepatitis who have failed standard therapy, is predicted by older age and lower immunoglobulin G and INR levels

AU - Nicoll, Amanda J.

AU - Roberts, Stuart K.

AU - Lim, Ricky

AU - Mitchell, Joanne

AU - Weltman, Martin

AU - George, Jacob

AU - Wigg, Alan

AU - Stuart, Katherine

AU - Gow, Paul

AU - MacQuillan, Gerry

AU - Tse, Edmund

AU - Levy, Miriam

AU - Sood, Siddharth

AU - Zekry, Amany

AU - Cheng, Wendy

AU - Mitchell, Jonathan

AU - Skoien, Richard

AU - Sievert, William

AU - Strasser, Simone I.

AU - McCaughan, Geoffrey W.

AU - on behalf of the ALA Clinical Research Network, Gastroenterological Society of Australia

PY - 2019/5/1

Y1 - 2019/5/1

N2 - Background: Mycophenolate mofetil is a commonly used salvage therapy for patients with autoimmune hepatitis (AIH). Aim: To evaluate the predictors of response to mycophenolate rescue therapy to facilitate clinical decision making. Methods: We performed a retrospective observational cohort study of AIH patients managed in 17 major Australian liver centres who received mycophenolate after an inadequate response or intolerance to corticosteroids with/without thiopurine(s). Baseline demographic, clinical and laboratory variables were compared between responders and nonresponders. A multivariable logistic regression model was developed using forward selection to identify independent predictors of treatment response. Results: A total of 105 patients received mycophenolate rescue therapy of whom 63 (60%) achieved biochemical remission. On univariable analysis, older age (P = 0.003), INR < 1.1 (P = 0.02), and lower immunoglobulin gamma (IgG; P < 0.002) levels were associated with treatment response, while no association was found with cirrhosis status (P = 0.07) or treatment indication (P = 0.63). On multivariable analysis, lower pre-treatment serum IgG level (P = 0.01), higher age at commencing mycophenolate (P = 0.01) and higher INR (P = 0.03) were the only significant independent predictors. An IgG level <17 g/L had a positive and negative predictive value for response of 71% and 60% respectively, while age ≥54 years when commencing mycophenolate had a positive and negative predictive value for response of 80% and 59% respectively. Conclusion: Mycophenolate remains an excellent treatment option for patients with AIH refractory to or intolerant of standard therapy with those most likely to benefit being older and/or having lower pre-treatment IgG levels.

AB - Background: Mycophenolate mofetil is a commonly used salvage therapy for patients with autoimmune hepatitis (AIH). Aim: To evaluate the predictors of response to mycophenolate rescue therapy to facilitate clinical decision making. Methods: We performed a retrospective observational cohort study of AIH patients managed in 17 major Australian liver centres who received mycophenolate after an inadequate response or intolerance to corticosteroids with/without thiopurine(s). Baseline demographic, clinical and laboratory variables were compared between responders and nonresponders. A multivariable logistic regression model was developed using forward selection to identify independent predictors of treatment response. Results: A total of 105 patients received mycophenolate rescue therapy of whom 63 (60%) achieved biochemical remission. On univariable analysis, older age (P = 0.003), INR < 1.1 (P = 0.02), and lower immunoglobulin gamma (IgG; P < 0.002) levels were associated with treatment response, while no association was found with cirrhosis status (P = 0.07) or treatment indication (P = 0.63). On multivariable analysis, lower pre-treatment serum IgG level (P = 0.01), higher age at commencing mycophenolate (P = 0.01) and higher INR (P = 0.03) were the only significant independent predictors. An IgG level <17 g/L had a positive and negative predictive value for response of 71% and 60% respectively, while age ≥54 years when commencing mycophenolate had a positive and negative predictive value for response of 80% and 59% respectively. Conclusion: Mycophenolate remains an excellent treatment option for patients with AIH refractory to or intolerant of standard therapy with those most likely to benefit being older and/or having lower pre-treatment IgG levels.

UR - http://www.scopus.com/inward/record.url?scp=85064821138&partnerID=8YFLogxK

U2 - 10.1111/apt.15248

DO - 10.1111/apt.15248

M3 - Article

VL - 49

SP - 1314

EP - 1322

JO - Alimentary Pharmacology and Therapeutics

JF - Alimentary Pharmacology and Therapeutics

SN - 0269-2813

IS - 10

ER -