Biochemical efficacy of tioguanine in autoimmune hepatitis: a retrospective review of practice in the Netherlands

Floris F van den Brand, Carin M J van Nieuwkerk, Bart J Verwer, Ynto S de Boer, Nanne K H de Boer, Chris J J Mulder, Elisabeth Bloemena, Christine M Bakker, Jan M Vrolijk, Joost P H Drenth, Adriaan C I T L Tan, Frank Ter Borg, Martijn J Ter Borg, Sven J van den Hazel, Akin Inderson, Maarten E Tushuizen, Gerd Bouma

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

BACKGROUND: Azathioprine (AZA) and mercaptopurine (MP) are the cornerstone of steroid-sparing strategies in autoimmune hepatitis (AIH). Up to 20% of patients do not tolerate or respond to these regimens.

AIM: To evaluate retrospectively the tolerability and efficacy of tioguanine (thioguanine) (TG) therapy in selected patients with AIH and AIH variant syndromes.

METHODS: Records of 52 patients who received TG therapy were retrieved from nine hospitals in the Netherlands. Indications for TG treatment were intolerable side effects on AZA or MP (n = 38), insufficient response (n = 11) or first-line treatment (n = 3). Treatment efficacy was defined as normalisation of serum aminotransferases and serum immunoglobulin G.

RESULTS: No serious adverse events occurred in patients treated with TG during a median follow-up of 18 months (range 1-194). Treatment was well tolerated in 41 patients (79%), whereas four had tolerable (8%) and seven (13%) intolerable side effects. Thirty-eight patients were treated with TG after intolerable side effects on AZA or MP; 29 patients continued TG therapy of whom 24 (83%) achieved complete biochemical remission, four (14%) had incomplete and one (3%) had no response; nine discontinued treatment. Seven of 11 patients with insufficient response to AZA or MP were responsive to TG, three with complete and four with incomplete biochemical remission; four discontinued due to intolerance (n = 2) and non-response (n = 2). TG was effective in all AIH patients as first-line maintenance treatment.

CONCLUSION: In our retrospective review of TG therapy in selected patients with AIH or AIH variants who previously failed on AZA or MP, TG appeared tolerable with biochemical efficacy.

Original languageEnglish
Pages (from-to)761-767
Number of pages7
JournalAlimentary pharmacology & therapeutics
Volume48
Issue number7
DOIs
Publication statusPublished - Oct 2018

Cite this

van den Brand, Floris F ; van Nieuwkerk, Carin M J ; Verwer, Bart J ; de Boer, Ynto S ; de Boer, Nanne K H ; Mulder, Chris J J ; Bloemena, Elisabeth ; Bakker, Christine M ; Vrolijk, Jan M ; Drenth, Joost P H ; Tan, Adriaan C I T L ; Ter Borg, Frank ; Ter Borg, Martijn J ; van den Hazel, Sven J ; Inderson, Akin ; Tushuizen, Maarten E ; Bouma, Gerd. / Biochemical efficacy of tioguanine in autoimmune hepatitis : a retrospective review of practice in the Netherlands. In: Alimentary pharmacology & therapeutics. 2018 ; Vol. 48, No. 7. pp. 761-767.
@article{6180042391cf42b198f849c556609519,
title = "Biochemical efficacy of tioguanine in autoimmune hepatitis: a retrospective review of practice in the Netherlands",
abstract = "BACKGROUND: Azathioprine (AZA) and mercaptopurine (MP) are the cornerstone of steroid-sparing strategies in autoimmune hepatitis (AIH). Up to 20{\%} of patients do not tolerate or respond to these regimens.AIM: To evaluate retrospectively the tolerability and efficacy of tioguanine (thioguanine) (TG) therapy in selected patients with AIH and AIH variant syndromes.METHODS: Records of 52 patients who received TG therapy were retrieved from nine hospitals in the Netherlands. Indications for TG treatment were intolerable side effects on AZA or MP (n = 38), insufficient response (n = 11) or first-line treatment (n = 3). Treatment efficacy was defined as normalisation of serum aminotransferases and serum immunoglobulin G.RESULTS: No serious adverse events occurred in patients treated with TG during a median follow-up of 18 months (range 1-194). Treatment was well tolerated in 41 patients (79{\%}), whereas four had tolerable (8{\%}) and seven (13{\%}) intolerable side effects. Thirty-eight patients were treated with TG after intolerable side effects on AZA or MP; 29 patients continued TG therapy of whom 24 (83{\%}) achieved complete biochemical remission, four (14{\%}) had incomplete and one (3{\%}) had no response; nine discontinued treatment. Seven of 11 patients with insufficient response to AZA or MP were responsive to TG, three with complete and four with incomplete biochemical remission; four discontinued due to intolerance (n = 2) and non-response (n = 2). TG was effective in all AIH patients as first-line maintenance treatment.CONCLUSION: In our retrospective review of TG therapy in selected patients with AIH or AIH variants who previously failed on AZA or MP, TG appeared tolerable with biochemical efficacy.",
author = "{van den Brand}, {Floris F} and {van Nieuwkerk}, {Carin M J} and Verwer, {Bart J} and {de Boer}, {Ynto S} and {de Boer}, {Nanne K H} and Mulder, {Chris J J} and Elisabeth Bloemena and Bakker, {Christine M} and Vrolijk, {Jan M} and Drenth, {Joost P H} and Tan, {Adriaan C I T L} and {Ter Borg}, Frank and {Ter Borg}, {Martijn J} and {van den Hazel}, {Sven J} and Akin Inderson and Tushuizen, {Maarten E} and Gerd Bouma",
note = "{\circledC} 2018 The Authors. Alimentary Pharmacology & Therapeutics Published by John Wiley & Sons Ltd.",
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language = "English",
volume = "48",
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Biochemical efficacy of tioguanine in autoimmune hepatitis : a retrospective review of practice in the Netherlands. / van den Brand, Floris F; van Nieuwkerk, Carin M J; Verwer, Bart J; de Boer, Ynto S; de Boer, Nanne K H; Mulder, Chris J J; Bloemena, Elisabeth; Bakker, Christine M; Vrolijk, Jan M; Drenth, Joost P H; Tan, Adriaan C I T L; Ter Borg, Frank; Ter Borg, Martijn J; van den Hazel, Sven J; Inderson, Akin; Tushuizen, Maarten E; Bouma, Gerd.

In: Alimentary pharmacology & therapeutics, Vol. 48, No. 7, 10.2018, p. 761-767.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Biochemical efficacy of tioguanine in autoimmune hepatitis

T2 - a retrospective review of practice in the Netherlands

AU - van den Brand, Floris F

AU - van Nieuwkerk, Carin M J

AU - Verwer, Bart J

AU - de Boer, Ynto S

AU - de Boer, Nanne K H

AU - Mulder, Chris J J

AU - Bloemena, Elisabeth

AU - Bakker, Christine M

AU - Vrolijk, Jan M

AU - Drenth, Joost P H

AU - Tan, Adriaan C I T L

AU - Ter Borg, Frank

AU - Ter Borg, Martijn J

AU - van den Hazel, Sven J

AU - Inderson, Akin

AU - Tushuizen, Maarten E

AU - Bouma, Gerd

N1 - © 2018 The Authors. Alimentary Pharmacology & Therapeutics Published by John Wiley & Sons Ltd.

PY - 2018/10

Y1 - 2018/10

N2 - BACKGROUND: Azathioprine (AZA) and mercaptopurine (MP) are the cornerstone of steroid-sparing strategies in autoimmune hepatitis (AIH). Up to 20% of patients do not tolerate or respond to these regimens.AIM: To evaluate retrospectively the tolerability and efficacy of tioguanine (thioguanine) (TG) therapy in selected patients with AIH and AIH variant syndromes.METHODS: Records of 52 patients who received TG therapy were retrieved from nine hospitals in the Netherlands. Indications for TG treatment were intolerable side effects on AZA or MP (n = 38), insufficient response (n = 11) or first-line treatment (n = 3). Treatment efficacy was defined as normalisation of serum aminotransferases and serum immunoglobulin G.RESULTS: No serious adverse events occurred in patients treated with TG during a median follow-up of 18 months (range 1-194). Treatment was well tolerated in 41 patients (79%), whereas four had tolerable (8%) and seven (13%) intolerable side effects. Thirty-eight patients were treated with TG after intolerable side effects on AZA or MP; 29 patients continued TG therapy of whom 24 (83%) achieved complete biochemical remission, four (14%) had incomplete and one (3%) had no response; nine discontinued treatment. Seven of 11 patients with insufficient response to AZA or MP were responsive to TG, three with complete and four with incomplete biochemical remission; four discontinued due to intolerance (n = 2) and non-response (n = 2). TG was effective in all AIH patients as first-line maintenance treatment.CONCLUSION: In our retrospective review of TG therapy in selected patients with AIH or AIH variants who previously failed on AZA or MP, TG appeared tolerable with biochemical efficacy.

AB - BACKGROUND: Azathioprine (AZA) and mercaptopurine (MP) are the cornerstone of steroid-sparing strategies in autoimmune hepatitis (AIH). Up to 20% of patients do not tolerate or respond to these regimens.AIM: To evaluate retrospectively the tolerability and efficacy of tioguanine (thioguanine) (TG) therapy in selected patients with AIH and AIH variant syndromes.METHODS: Records of 52 patients who received TG therapy were retrieved from nine hospitals in the Netherlands. Indications for TG treatment were intolerable side effects on AZA or MP (n = 38), insufficient response (n = 11) or first-line treatment (n = 3). Treatment efficacy was defined as normalisation of serum aminotransferases and serum immunoglobulin G.RESULTS: No serious adverse events occurred in patients treated with TG during a median follow-up of 18 months (range 1-194). Treatment was well tolerated in 41 patients (79%), whereas four had tolerable (8%) and seven (13%) intolerable side effects. Thirty-eight patients were treated with TG after intolerable side effects on AZA or MP; 29 patients continued TG therapy of whom 24 (83%) achieved complete biochemical remission, four (14%) had incomplete and one (3%) had no response; nine discontinued treatment. Seven of 11 patients with insufficient response to AZA or MP were responsive to TG, three with complete and four with incomplete biochemical remission; four discontinued due to intolerance (n = 2) and non-response (n = 2). TG was effective in all AIH patients as first-line maintenance treatment.CONCLUSION: In our retrospective review of TG therapy in selected patients with AIH or AIH variants who previously failed on AZA or MP, TG appeared tolerable with biochemical efficacy.

U2 - 10.1111/apt.14939

DO - 10.1111/apt.14939

M3 - Article

VL - 48

SP - 761

EP - 767

JO - Alimentary pharmacology & therapeutics

JF - Alimentary pharmacology & therapeutics

SN - 1365-2036

IS - 7

ER -