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Clinical and epidemiological research
Extended report
Quantifying the hepatotoxic risk of alcohol consumption in patients with rheumatoid arthritis taking methotrexate
  1. Jenny H Humphreys1,
  2. Alexander Warner1,
  3. Ruth Costello1,
  4. Mark Lunt1,
  5. Suzanne M M Verstappen1,
  6. William G Dixon1,2,3
  1. 1 Arthritis Research UK Centre for Epidemiology, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK
  2. 2 NIHR Manchester Musculoskeletal Biomedical Research Unit, Central Manchester Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK
  3. 3 Health eResearch Centre, Farr Institute, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK
  1. Correspondence to Professor William G Dixon, Arthritis Research UK Centre for Epidemiology, Manchester Academic Health Science Centre, University of Manchester, Stopford Building, Oxford Road, Manchester M13  9PT, UK; will.dixon{at}manchester.ac.uk

Abstract

Background Patients with rheumatoid arthritis (RA) who take methotrexate (MTX) are advised to limit their alcohol intake due to potential combined hepatotoxicity. However, data are limited to support this. The aim of this study was to quantify the risk of developing abnormal liver blood tests at different levels of alcohol consumption, using routinely collected data from primary care.

Methods Patients with RA in the Clinical Practice Research Datalink starting MTX between 1987 and 2016 were included. Hepatotoxicity was defined as transaminitis: alanine transaminase or aspartate aminotransferase more than three times the upper limit of normal. Crude rates of transaminitis were calculated per 1000 person-years, categorised by weekly alcohol consumption in units. Cox proportional hazard models tested the association between alcohol consumption and transaminitis univariately, then age and gender adjusted.

Results 11 839 patients were included, with 530 episodes of transaminitis occurring in 47 090 person-years follow-up. Increased weekly alcohol consumption as a continuous variable was associated with increased risk of transaminitis, adjusted HR (95% CI) per unit consumed 1.01 (1.00 to 1.02); consuming between 15 and 21 units was associated with a possible increased risk of hepatotoxicity, while drinking >21 units per week significantly increased rates of transaminitis, adjusted HR (95% CI) 1.85 (1.17 to 2.93).

Conclusions Weekly alcohol consumption of <14 units per week does not appear to be associated with an increased risk of transaminitis.

  • Rheumatoid Arthritis
  • Methotrexate
  • Epidemiology
  • Treatment

This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0/

https://doi.org/10.1136/annrheumdis-2016-210629

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    Footnotes

    • Handling editor Tore K Kvien

    • Twitter Follow William Dixon @WGDixon

    • Contributors WGD conceived the idea; WGD, AW and JHH were responsible for the design of the study; JHH and RC conducted the analysis; JHH drafted the manuscript; all authors interpreted the results, critically revised the manuscript for important intellectual content and approved the final manuscript.

    • Funding This work was supported by the Arthritis Research UK Centre for Epidemiology (20380). JHH is funded as an NIHR Academic Clinical Lecturer. WGD was supported by a Medical Research Council Clinician Scientist Fellowship (G0902272).

    • Competing interests None declared.

    • Ethics approval The protocol for this study has been approved by Independent Scientific Advisory Committee for Medicines and Healthcare Regulatory Agency database research (Protocol number: 12_004Mn).

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data sharing statement Clinical Practice Research Datalink (CPRD) data can be accessed with an appropriate licence from the CPRD and with approval from the Independent Scientific Advisory Committee. Licences are available from CPRD: The Clinical Practice Research Datalink Group, The Medicines and Healthcare Products Regulatory Agency, 5th Floor, 151 Buckingham Palace Road, Victoria, London SW1W 9SZ, England or http://www.cprd.com.