Prognostic factors for liver, blood and kidney adverse events from glucocorticoid sparing immune-suppressing drugs in immune-mediated inflammatory diseases: a prognostic systematic review

Background Immune-suppressing drugs can cause liver, kidney or blood toxicity. Prognostic factors for these adverse-events are poorly understood.Purpose To ascertain prognostic factors associated with liver, blood or kidney adverse-events in people receiving immune-suppressing drugs.Data sources MED...

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Main Authors: Abhishek Abhishek, Danielle van der Windt, Christopher Carroll, Matthew J Grainge, Richard Riley, Joanna Leaviss, Munira Essat, Tim Card
Format: Article
Language:English
Published: BMJ Publishing Group 2024-02-01
Series:RMD Open
Online Access:https://rmdopen.bmj.com/content/10/1/e003588.full
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author Abhishek Abhishek
Danielle van der Windt
Christopher Carroll
Matthew J Grainge
Richard Riley
Joanna Leaviss
Munira Essat
Tim Card
author_facet Abhishek Abhishek
Danielle van der Windt
Christopher Carroll
Matthew J Grainge
Richard Riley
Joanna Leaviss
Munira Essat
Tim Card
author_sort Abhishek Abhishek
collection DOAJ
description Background Immune-suppressing drugs can cause liver, kidney or blood toxicity. Prognostic factors for these adverse-events are poorly understood.Purpose To ascertain prognostic factors associated with liver, blood or kidney adverse-events in people receiving immune-suppressing drugs.Data sources MEDLINE, Web of Science, EMBASE and the Cochrane library (01 January 1995 to 05 January 2023), and supplementary sources.Data extraction and synthesis Data were extracted by one reviewer using a modified CHARMS-PF checklist and validated by another. Two independent reviewers assessed risk of bias using Quality in Prognostic factor Studies tool and assessed the quality of evidence using a Grading of Recommendations Assessment, Development and Evaluation-informed framework.Results Fifty-six studies from 58 papers were included. High-quality evidence of the following associations was identified: elevated liver enzymes (6 studies) and folate non-supplementation (3 studies) are prognostic factors for hepatotoxicity in those treated with methotrexate; that mercaptopurine (vs azathioprine) (3 studies) was a prognostic factor for hepatotoxicity in those treated with thiopurines; that mercaptopurine (vs azathioprine) (3 studies) and poor-metaboliser status (4 studies) were prognostic factors for cytopenia in those treated with thiopurines; and that baseline elevated liver enzymes (3 studies) are a prognostic factor for hepatotoxicity in those treated with anti-tumour necrosis factors. Moderate and low quality evidence for several other demographic, lifestyle, comorbidities, baseline bloods/serologic or treatment-related prognostic factors were also identified.Limitations Studies published before 1995, those with less than 200 participants and not published in English were excluded. Heterogeneity between studies included different cut-offs for prognostic factors, use of different outcome definitions and different adjustment factors.Conclusions Prognostic factors for target-organ damage were identified which may be further investigated for their potential role in targeted (risk-stratified) monitoring.PROSPERO registration number CRD42020208049.
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spelling doaj-art-d5146f9c3d144a6ea79126f8f4a3b74c2025-08-20T01:48:48ZengBMJ Publishing GroupRMD Open2056-59332024-02-0110110.1136/rmdopen-2023-003588Prognostic factors for liver, blood and kidney adverse events from glucocorticoid sparing immune-suppressing drugs in immune-mediated inflammatory diseases: a prognostic systematic reviewAbhishek Abhishek0Danielle van der Windt1Christopher Carroll2Matthew J Grainge3Richard Riley4Joanna Leaviss5Munira Essat6Tim Card7Academic Rheumatology, University of Nottingham, Nottingham, UKSchool of Medicine, Keele University, Keele, UKSCHARR, The University of Sheffield, Sheffield, Yorkshire, UKLifespan and Population Health, University of Nottingham, Nottingham, UK2 Department of Applied Health Sciences, School of Health Sciences, College of Medicine and Health, University of Birmingham, Birmingham, UKSCHARR, The University of Sheffield, Sheffield, Yorkshire, UKUniversity of Sheffield, Sheffield, UKLifespan and Population Health, University of Nottingham, Nottingham, UKBackground Immune-suppressing drugs can cause liver, kidney or blood toxicity. Prognostic factors for these adverse-events are poorly understood.Purpose To ascertain prognostic factors associated with liver, blood or kidney adverse-events in people receiving immune-suppressing drugs.Data sources MEDLINE, Web of Science, EMBASE and the Cochrane library (01 January 1995 to 05 January 2023), and supplementary sources.Data extraction and synthesis Data were extracted by one reviewer using a modified CHARMS-PF checklist and validated by another. Two independent reviewers assessed risk of bias using Quality in Prognostic factor Studies tool and assessed the quality of evidence using a Grading of Recommendations Assessment, Development and Evaluation-informed framework.Results Fifty-six studies from 58 papers were included. High-quality evidence of the following associations was identified: elevated liver enzymes (6 studies) and folate non-supplementation (3 studies) are prognostic factors for hepatotoxicity in those treated with methotrexate; that mercaptopurine (vs azathioprine) (3 studies) was a prognostic factor for hepatotoxicity in those treated with thiopurines; that mercaptopurine (vs azathioprine) (3 studies) and poor-metaboliser status (4 studies) were prognostic factors for cytopenia in those treated with thiopurines; and that baseline elevated liver enzymes (3 studies) are a prognostic factor for hepatotoxicity in those treated with anti-tumour necrosis factors. Moderate and low quality evidence for several other demographic, lifestyle, comorbidities, baseline bloods/serologic or treatment-related prognostic factors were also identified.Limitations Studies published before 1995, those with less than 200 participants and not published in English were excluded. Heterogeneity between studies included different cut-offs for prognostic factors, use of different outcome definitions and different adjustment factors.Conclusions Prognostic factors for target-organ damage were identified which may be further investigated for their potential role in targeted (risk-stratified) monitoring.PROSPERO registration number CRD42020208049.https://rmdopen.bmj.com/content/10/1/e003588.full
spellingShingle Abhishek Abhishek
Danielle van der Windt
Christopher Carroll
Matthew J Grainge
Richard Riley
Joanna Leaviss
Munira Essat
Tim Card
Prognostic factors for liver, blood and kidney adverse events from glucocorticoid sparing immune-suppressing drugs in immune-mediated inflammatory diseases: a prognostic systematic review
RMD Open
title Prognostic factors for liver, blood and kidney adverse events from glucocorticoid sparing immune-suppressing drugs in immune-mediated inflammatory diseases: a prognostic systematic review
title_full Prognostic factors for liver, blood and kidney adverse events from glucocorticoid sparing immune-suppressing drugs in immune-mediated inflammatory diseases: a prognostic systematic review
title_fullStr Prognostic factors for liver, blood and kidney adverse events from glucocorticoid sparing immune-suppressing drugs in immune-mediated inflammatory diseases: a prognostic systematic review
title_full_unstemmed Prognostic factors for liver, blood and kidney adverse events from glucocorticoid sparing immune-suppressing drugs in immune-mediated inflammatory diseases: a prognostic systematic review
title_short Prognostic factors for liver, blood and kidney adverse events from glucocorticoid sparing immune-suppressing drugs in immune-mediated inflammatory diseases: a prognostic systematic review
title_sort prognostic factors for liver blood and kidney adverse events from glucocorticoid sparing immune suppressing drugs in immune mediated inflammatory diseases a prognostic systematic review
url https://rmdopen.bmj.com/content/10/1/e003588.full
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