Methotrexate-Treated Rheumatoid Arthritis: No Liver Damage With Moderate Alcohol Use

Liver and alcohol addiction double exposure
Liver and alcohol addiction double exposure
Study analyzed medical records to determine whether alcohol consumption increases hepatotoxic risk in patients with rheumatoid arthritis being treated with methotrexate.

An analysis of medical records data showed that consumption of less than 14 units of alcohol per week did not place patients with rheumatoid arthritis (RA) treated with methotrexate (MTX) at hepatotoxic risk. Results of the research, led by Jenny H. Humphrey, MRCP, PhD, of the University of Manchester in the United Kingdom, were published ahead of print in Annals of the Rheumatic Diseases.1

“This is the first study to provide estimates of risk of liver damage for different levels of alcohol consumption in this drug. It also quantifies the risk for doctors so they can be clear about the extent to which different levels of alcohol will cause problems across a population of patients taking methotrexate,” co-investigator Will Dixon, MRCP, PhD, stated in a press release.2

American College of Rheumatology (ACR) guidelines for monitoring liver toxicity in patients with RA using methotrexate recommend that they abstain from alcohol entirely, while guidelines from the British Society for Rheumatology (BSR) simply state that patients taking methotrexate for RA should stay “well within the UK national recommendations” for alcohol consumption. The researchers noted that in the absence of evidence, patients might choose to abstain from alcohol, avoid MTX altogether, or simply experience anxiety with even modest alcohol use. 

High-Yield Data Summary

  • There was no increase in the risk of transaminitis in patients with rheumatoid arthritis who consumed <14 units alcohol per week while taking methotrexate.

“Understanding whether there is a safe amount of alcohol that can be consumed alongside MTX, and what that amount is, would significantly aid informed decision-making,” wrote Dr. Humphrey and colleagues.

In order to determine the risk of developing liver damage at different levels of alcohol consumption in patients with RA who use  MTX, the investigators identified patient data for individuals with RA starting MTX after 1987 in the Clinical Practice Research Datalink (CPRD). The CPRD is a database of primary care electronic medical records representing 8% of the total UK population. Patients were included in the analysis if their records included data on their alcohol consumption and measurements of at least 6 alanine transaminase (ALT) and aspartate aminotransferase (AST) levels per year. 

A total of 11,839 patients were ultimately included in the analysis. The outcome of interest was the development of transaminitis, a sign of liver damage defined for the purposes of the study as ALT or AST levels ≥3 times the upper limit of normal.

Results showed that the crude rate of transaminitis per 1000 person-years was 10.08 in patients who reported no alcohol consumption, 10.25 in consumers of 1 to 7 units of alcohol per week (age/gender adjusted hazard ratio [HR], 1.03; 95% CI, 0.82, 1.28), and 9.94 in consumers of 7 to 14 units of alcohol per week (age/gender adjusted HR, 1.01; 95% CI, 0.73, 1.40), differences that were not statistically significant. A potential risk for liver damage was seen in patients consuming 15 to 21 units per week (age/gender adjusted HR, 1.35; 95% CI, 0.85, 2.14), and a significant risk was seen in patients consuming over 21 units per week (age/gender adjusted HR, 1.85; 95% CI, 1.17, 2.93).

Summary and Clinical Applicability 

“In the largest study of its kind to date, we have shown no increase in the risk of transaminitis in patients who consume <14 units alcohol per week while taking MTX,” wrote the investigators. “This may provide the practical and useful information that drinking alcohol within nationally recommended levels in the UK is safe, in terms of risk of transaminitis, for patients commencing MTX therapy for RA.”

Study Limitations

  • Because the records analyzed came from a primary care database, some cases of RA may have been misclassified
  • Alcohol use was self-reported and may have been underestimated
  • Due to the use of transaminitis as the outcome measure, not all hepatotoxicity may have been captured
  • The outcome measure required 3 sequential raised values for ALT or AST; however, clinicians who note rises in these values may be inclined to withdraw methotrexate therapy, in which case the outcome measure would not have been fulfilled  
  • The study was only conducted in patients diagnosed with RA and cannot be generalized to other patients using methotrexate 

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  1. Humphreys JH, Warner A, Costello R, Lunt M, Verstappen SM, Dixon WG. Quantifying the hepatotoxic risk of alcohol consumption in patients with rheumatoid arthritis taking methotrexate [published online March 23, 2017]. Ann Rheum Dis. doi:10.1136/annrheumdis-2016-210629
  2. Moderate drinkers not at risk when taking a widely-used arthritis medicine [news release]. Manchester, UK: University of Manchester; March 27, 2017. Accessed April 5, 2017.

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