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: 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.