NEW YORK (Reuters Health)—In patients taking methotrexate for rheumatoid arthritis (RA), moderate alcohol consumption – that is, no higher than existing U.K. guidelines for the general population – was not associated with an increased risk of transaminitis, researchers say.
The study is both the largest to examine alcohol and methotrexate (MTX) and the first to look at how the amount of alcohol affects hepatotoxicity in patients taking long-term MTX, corresponding author Dr. William G. Dixon, of the University of Manchester, told Reuters Health by email.
Although the risk of transaminitis in patients with RA taking MTX was found to increase with increasing alcohol consumption, the risk in those patients who consumed no more than 14 units of alcohol per week was no greater than in those who do not drink alcohol, the researchers reported online March 23 in Annals of the Rheumatic Diseases.
U.K. guidelines recommend the consumption of no more than 14 units of alcohol per week, by men or women. A “unit” of alcohol is defined as 10 ml or 8 g of pure alcohol.
Fourteen units of alcohol equals six pints of 4% beer, six glasses of 13% wine, or 14 (25 ml) glasses of 40% spirits, according to the Drinkaware website.
In comparison, guidelines from the U.S. Centers for Disease Control and Prevention indicate that moderate alcohol use is up to 1 drink for a woman and 2 drinks for a man, on any single day. “Drink” definitions are similar to those used in the United Kingdom.
Their findings, the researchers wrote, “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.” Including these acceptable alcohol levels in clinical guidelines and informing patients of them, they added, could improve decision-making, clinical outcomes and overall quality of life.
The current uncertainty, Dr. Dixon said, “means that patients often avoid alcohol altogether, or avoid methotrexate if they want to continue to drink, even modestly.”
The authors cautioned, however, that their findings should not be generalized to other populations. For example, previous research has suggested that patients with psoriasis may have a higher incidence of liver disease compared to patients with RA.
One expert who was not connected to the study raised another caveat. Dr. Joel Kremer, of Albany Medical Center in upstate New York, thinks the study’s threshold for transaminitis – i.e., alanine transaminase or aspartate aminotransferase at least three times the upper limit of normal (ULN) – is much too high.
Dr. Kremer, who coauthored 1994 guidelines for monitoring liver toxicity in RA patients receiving MTX, told Reuters Health by phone that in the mid-1990s, research found that any elevation of transaminase was associated with deterioration of liver biopsy.
“Transaminitis has been defined in different ways in the literature,” Dr. Dixon noted. The researchers chose three times ULN to avoid including mild transaminitis, but “lower values might still be clinically important,” he said.
Dr. Dixon pointed out that a sensitivity analysis defining transaminitis as any persistent elevation (three sequential levels greater than ULN) produced the same findings, that fewer than 14 units of alcohol per week was not associated with an increased risk of transaminitis.
“I suspect that a number of my patients (receiving MTX for RA) simply do not admit to having an alcoholic beverage on a fairly regular basis,” Dr. Christopher Morris, a member of the American College of Rheumatology’s Committee on Government Affairs, told Reuters Health in an email. “I am not too certain that it causes patients not to comply with the methotrexate, as much as it results in the patient hiding their alcohol use.”
“This article can lead us to feel a bit better when we have a patient who admits having a drink or two over the weekend, as long as we stress that limiting the number of drinks a week is important,” he added.
Dr. Morris admitted to being uncomfortable with the setting of the alanine transaminase or aspartate aminotransferase threshold at 3x ULN, but added that “studies have suggested that liver biopsies do not correlate all that well with mild elevations” of liver function tests.
Dr. John J. Cush, executive editor of RheumNow.com, cited that website’s February survey of nearly 500 U.S. and non-U.S. rheumatologists, which found that roughly half of those surveyed will permit one to three alcoholic drinks per week for patients on MTX. A quarter allow only one to three drinks per month, while 15-20% forbid any alcohol use and 6-7% have no restrictions on alcohol, provided there is no underlying liver disease.
The study used a clinical practice database to evaluate the records of 11,839 patients (71% female, mean age 61) with RA and who had received MTX. The researchers found 530 first episodes of transaminitis during 47,090 person-years of follow-up.
Alcohol consumption below 14 units per week was associated with a very low probability (0.93%) of having an at least 50% increased risk of transaminitis. For greater weekly alcohol consumption, the probability of having such an increased risk of transaminitis was higher: 33% and 81% for consumption of 15-21 units and more than 21 units, respectively.
The study was funded by the Arthritis Research UK Centre for Epidemiology and other governmental sources. The authors declared no competing interests.
Reference
Humphreys JH, Warner A, Costello R, et al. Quantifying the hepatotoxic risk of alcohol consumption in patients with rheumatoid arthritistaking methotrexate. Annals of Rheumatic Diseases. 2017 Mar 23. [Epub ahead of print].
