TY - JOUR
T1 - Methotrexate and Thioguanine Rescue Therapy for Conventional Thiopurine Failing Ulcerative Colitis Patients
T2 - A Multi-center Database Study on Tolerability and Effectiveness
AU - Meijer, Berrie
AU - Mulder, Chris J J
AU - Bouma, Gerd
AU - Ponsioen, Cyriel Y
AU - van der Woude, C Janneke
AU - van der Meulen, Andrea E
AU - Wintjens, Dion S J
AU - Dijkstra, Gerard
AU - Hoentjen, Frank
AU - Oldenburg, Bas
AU - van Bodegraven, Adriaan A
AU - de Boer, Nanne K H
N1 - Funding Information:
Received for publications September 14, 2017; Editorial Decision October 31, 2017. *Department of Gastroenterology and Hepatology, VU University Medical Center, Amsterdam; †Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam; ‡Department of Gastroenterology and Hepatology, Erasmus Medical Center, Rotterdam; §Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden; ¶Division of Gastroenterology and Hepatology, Maastricht University Medical Center, Maastricht;**Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, Groningen; ††Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen; ‡‡Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht; §§Department of Gastroenterology, Geriatrics, Internal and Intensive Care Medicine (Co-MIK), Zuyderland Medical Center, Heerlen-Sittard-Geleen FINANCIAL DISCLOSURES Chris J. J Mulder has served as a principal investigator for TEVA Pharma BV. He has received a research grant from TEVA Pharma BV. C. Janneke van der Woude has received unrestricted grants from Pfizer and Tramedico and e has served as a member of advisory board for Mundipharma, Celgene, Takeda, Abbvie, and MSD. Gerard Dijkstra has received unrestricted research grants from AbbVie and Takeda, has served as a member of the advisory board for Mundipharma and Pharmacosmos, and has received speaker fees from Takeda and Janssen.Frank Hoentjen has served as a speaker, member of advisory board, or consultant for MSD, Takeda, Celltrion, Teva, Sandoz, Dr Falk. and Celgene. Bas Oldenburg has served as a speaker, member of advisory board, or consultant for AbbVie, Ferring, Janssen, MSD, Pfizer, and Takeda. Adriaan A. van Bodegraven has served as a speaker, member of advisory board, or consultant for AbbVie, Ferring, Janssen, MSD, Pfizer, Tramedico, and Takeda. Nanne K. H. de Boer has served as a speaker for AbbVie and MSD, has served as consultant and principal investigator for TEVA Pharma BV and Takeda, and has received a (unrestricted) research grant from Dr. Falk and Takeda. Gerd Bouma, Berrie Meijer, Cyriel Y. Ponsioen , Andrea E. van der Meulen, and Dion S. J. Wintjens have nothing to disclose Conflicts of Interest: The department of Gastroenterology and Hepatology of the VU University Medical Center received an unrestricted research grant from TEVA Pharma BV for thioguanine research. All centers are located in The Netherlands. Supported by: The work described in this study was carried out in collaboration with the Parelsnoer Institute (PSI). PSI is part of and funded by the Dutch Federation of University Medical Centers and has received initial funding from the Dutch Government (from 2007–2011). *Correspondence address. Department of Gastroenterology and Hepatology, VU University Medical Center, Room PK 2X 136, De Boelelaan 1118, 1081HZ Amsterdam. E-mail: [email protected] © 2018 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: [email protected].
Publisher Copyright:
©'2018 Crohn's & Colitis Foundation. Published by Oxford University Press.
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2018/7
Y1 - 2018/7
N2 - Background: Patients with active ulcerative colitis (UC) failing conventional therapies are in need of rescue strategies. Due to the fact that accepted step-up therapy with biologicals is expensive and sometimes unavailable, alternative therapies are warranted. Methotrexate (MTX) and thioguanine (TG) have both been suggested as alternative maintenance strategies in conventional thiopurine failing UC patients. In this multicenter database study, we compared safety and effectiveness (drug-survival) of MTX and TG in UC patients.Methods: We collected data from the Parelsnoer database, a prospective Dutch national database consisting of inflammatory bowel disease patients from all university hospitals in The Netherlands. Additional data were collected from detailed chart review.Results: In total, 99 UC patients were included, of which 48 used TG, 43 used MTX, and 8 patients had a history of both TG and MTX use. In 12% of the patients, biological therapy had failed. Roughly 70% of the patients in both groups were able to continue therapy for over 1 year. Adverse events were noted in 33% of all the patients and were mainly elevated liver enzymes or gastrointestinal complaints. Twenty-eight patients (28%) continued therapy (15 TG, 13 MTX) without the need of escalation therapy (eg, corticosteroids, biologicals, or surgery). Drug survival curves of both drugs were comparable, just as the number of patients with sustained clinical benefit of therapy (P > 0.05).Conclusion: Both MTX and TG may be used and maintained as rescue therapy with sustained clinical benefit in one-third of the UC patients failing conventional therapies.
AB - Background: Patients with active ulcerative colitis (UC) failing conventional therapies are in need of rescue strategies. Due to the fact that accepted step-up therapy with biologicals is expensive and sometimes unavailable, alternative therapies are warranted. Methotrexate (MTX) and thioguanine (TG) have both been suggested as alternative maintenance strategies in conventional thiopurine failing UC patients. In this multicenter database study, we compared safety and effectiveness (drug-survival) of MTX and TG in UC patients.Methods: We collected data from the Parelsnoer database, a prospective Dutch national database consisting of inflammatory bowel disease patients from all university hospitals in The Netherlands. Additional data were collected from detailed chart review.Results: In total, 99 UC patients were included, of which 48 used TG, 43 used MTX, and 8 patients had a history of both TG and MTX use. In 12% of the patients, biological therapy had failed. Roughly 70% of the patients in both groups were able to continue therapy for over 1 year. Adverse events were noted in 33% of all the patients and were mainly elevated liver enzymes or gastrointestinal complaints. Twenty-eight patients (28%) continued therapy (15 TG, 13 MTX) without the need of escalation therapy (eg, corticosteroids, biologicals, or surgery). Drug survival curves of both drugs were comparable, just as the number of patients with sustained clinical benefit of therapy (P > 0.05).Conclusion: Both MTX and TG may be used and maintained as rescue therapy with sustained clinical benefit in one-third of the UC patients failing conventional therapies.
KW - Journal Article
KW - Inflammatory bowel disease
KW - Thiopurines
KW - Methotrexate
KW - Rescue therapy
KW - Thioguanine
KW - Ulcerative colitis
KW - Prospective Studies
KW - Humans
KW - Middle Aged
KW - Drug Tolerance
KW - Proportional Hazards Models
KW - Male
KW - Thioguanine/therapeutic use
KW - Treatment Outcome
KW - Remission Induction
KW - Netherlands
KW - Colitis, Ulcerative/drug therapy
KW - Adult
KW - Female
KW - Immunosuppressive Agents/therapeutic use
KW - Drug Therapy, Combination
KW - Databases, Factual
KW - Methotrexate/therapeutic use
KW - thiopurines
KW - methotrexate
KW - ulcerative colitis
KW - rescue therapy
KW - inflammatory bowel disease
KW - thioguanine
UR - https://www.scopus.com/pages/publications/85053669716
U2 - 10.1093/ibd/izy047
DO - 10.1093/ibd/izy047
M3 - Article
C2 - 29668998
SN - 1078-0998
VL - 24
SP - 1558
EP - 1565
JO - Inflammatory bowel diseases
JF - Inflammatory bowel diseases
IS - 7
ER -