RA, Methotrexate and Alcohol May Mix Well, to a Degree


The combination of alcohol and methotrexate is generally frowned upon, but a new study suggests alcohol in small quantities may be OK.

The 1994 American College of Rheumatology treatment guidelines for rheumatoid arthritis recommend that patients taking methotrexate abstain from drinking alcohol, but in 2008, the British Society for Rheumatology recommended just limiting alcohol intake in these cases.

Hepatoxicity is a concern for rheumatoid arthritis patients who are prescribed methotrexate and adding alcohol to the mix, could heighten the risk of liver damage.

Doctors have reported that patients say they feel “anxious” or “ill at ease” when mixing alcohol with methotrexate. Abstaining from alcohol can be difficult for some patients, say researchers from the University of Manchester who explored whether there is indeed a safe amount of alcohol that can be consumed with methotrexate and if so, how much?

Their findings, published online March 23 in Annals of the Rheumatic Diseasesshow that patients may be able to safely consume 14 units of alcohol or fewer per week without an increased risk of liver damage.

“In this study, we have demonstrated that the risk of transaminitis in patients with RA taking MTX does increase with increasing levels of alcohol consumption. However, the risk in those patients who consume at least ≤14 units of alcohol per week is no greater than those who do not drink alcohol,” wrote researchers who were led by William G. Dixon, Ph.D.

This is the first large-scale study to provide quantifiable estimates of the risk of different levels of alcohol consumption while taking methotrexate long-term.

The Study

This was a retrospective observational study based on data collected from the Clinical Practice Research Datalink, a large electronic database of primary care medical records in the UK. The data for this study was collected between 1987 and 2016. A total of 44,586 patients with rheumatoid arthritis were identified of which 11,839 were included in the study (8,401 female, mean age 61 years).

The primary outcome was transaminitis (elevation in liver enzymes indicating liver damage) levels three times above the upper limits of normal.


At 78 percent, most of the patients were mild drinkers consuming fewer than seven drinks per week while 8 percent consumed more than 14 drinks per week.

Of, 11,839 patients, 530 reported episodes of transaminitis occurring in 47,090 person-years follow-up. Patients were included only if they had six or more liver function tests per year.

There was no increased risk in the occurrence of liver damage in drinkers compared with non-drinkers (95% confidence interval 1.06). Every additional drink consumed increased the risk of liver damage in patients with rheumatoid arthritis on methotrexate (95% CI 1.01). The probability of developing significant transaminitis for patients with rheumatoid arthritis on methotrexate that drink less than 14 drinks a week, 15-21 drinks a week and greater than 21 drinks a week was 0.93%, 33%, and 81% respectively.

The rates of liver damage increase with increasing levels of alcohol consumption when patients drinking more than 21 drinks a week are compared to non-drinkers (95% confidence interval 1.85).


Since this was a study based on a review of medical data, the findings are based on rheumatoid arthritis cases as recorded by general practitioners. Information bias was also a possibility in that alcohol consumption was self-reported and the study design constrained the rheumatoid arthritis population to methotrexate users. And, higher liver function test levels may be have been due to the existence of unrecorded co-morbidities.

Implications for Physicians

Patients with rheumatoid arthritis on methotrexate therapy may be able to consume up to 14 alcoholic beverages a week without an increased risk of liver damage, the authors suggest.

The more alcoholic beverages patients with rheumatoid arthritis on methotrexate consume each week over 14 drinks, the higher the risk of liver damage in a dose dependent fashion.

Dose of methotrexate was not included in the analysis so physicians should use caution in counseling patients on alcohol consumption when on higher doses of methotrexate.

The authors conclude that, “Inclusion of acceptable alcohol levels into clinical guidelines and patient information may well improve informed decision-making, clinical outcomes, reduce decision conflict and improve overall quality of life.”



The Arthritis Research UK Centre for Epidemiology provided general funding with individual support for Jenny Humphreys and William Dixon coming from being a NIHR Academic Clinical Lecturer and a Medical Research Council Clinician Scientist Fellow respectively.


Jenny H Humphreys, Aleander Warner, Ruth Costello, et al. “Quantifying the hepatotoxic risk of alcohol consumption in patients with rheumatoid arthritis taking methotrexate,” Annals of the Rheumatic Diseases.  2017;0:1–6. doi:10.1136/annrheumdis-2016-210629 

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