GLASGOW – Advising patients with rheumatoid arthritis who are being treated with methotrexate to moderate their alcohol intake remains sound advice, the results of a large clinical database study showed.
Increasing alcohol intake was found to be associated with an increased risk for developing abnormal results on serum liver function tests (LFTs). However, the clinical importance of this was thought to be small if the number of alcoholic units per week remained below 14 – which is general advice for men and women in the United Kingdom.
“We advise our patients to restrict their alcohol consumption, because we know that alcohol is hepatotoxic …, methotrexate is hepatotoxic, and there is a presumed interaction there,” the presenting study author, Dr. Jenny H. Humphreys, said in an interview at the British Society for Rheumatology annual conference. “But actually, the data to support that advice [are] fairly limited and may not reflect our current patient population,” added Dr. Humphreys of the Arthritis Research U.K. Centre for Epidemiology at the University of Manchester (England).
Dr. Jennifer H. Humphreys
In a poster presentation, Dr. Humphreys aimed to quantify the association between alcohol intake and serum alanine or aspartate aminotransferase (ALT/AST) levels using routinely collected clinical data from the Clinical Practice Research Datalink (CPRD). Data on more than 8,000 patients starting methotrexate (MTX) for treating rheumatoid arthritis (RA) between 1987 and 2011 were obtained and analyzed.
Patients were included in the analysis if they had information on their alcohol consumption recorded and if serum LFTs had been assessed routinely by their primary care physician at least six times per year. They were then grouped based on their weekly reported alcohol consumption from none (0 units) to excessive (more than 28 units). In the United Kingdom, a unit of alcohol is defined as 10 mL (8 g) of pure alcohol, and the typical alcoholic beverage may contain 1-3 units of alcohol. The mean age of participants in the study was 58 years, and 71% were female.
When 38,000 person-years of follow-up were evaluated, 241 abnormal LFT events, defined as ALT/AST levels more than three times the upper limit of normal, were identified.
Crude incidence rates of abnormal LFTs per 1,000 person-years were 5.58 in nondrinkers, 5.57 in those who drank 1-7 units of alcohol per week, 5.99 in those who drank 8-14 units, 7.58 in those who drank 15-21 units, 8.61 in those who drank 22-28 units, and 9.05 in those who drank more than 28 units. Although the hazard ratios adjusted for age and sex also increased with increasing alcohol intake, from 1.02 in the lightest drinkers to 1.92 in the heaviest drinkers, no statistical significance was found overall between the drinkers and nondrinkers.
“When treated as a continuous variable, there was a statistically significant increase of 1% abnormal LFTs for every unit of alcohol consumed, but you wonder how clinically relevant is a 1% increase,” Dr. Humphreys said.
To look at the data another way, a clinically relevant increase was set for abnormal LFTs; then the data for increasing alcohol consumption were used to see how many patients had crossed that boundary. The investigators found an increase with higher alcohol consumption levels, but that power was limited to patients who drank 14 units a week or fewer. “So essentially, increasing alcohol consumption does increase your risk of abnormal LFTs. But when you are drinking less than about 14 units a week, there is little clinical significance of that, “ Dr. Humphreys said. So for patients who do want to continue drinking while on MTX, it should be reasonably safe to advise them that they can do so as long as they moderate their intake.
Separate research presented in a poster by Dr. Ravi Narang of Frimley Health NHS Foundation Trust in Surrey, England, and associates looked at the use of hepatic elastography (FibroScan) in MTX-treated patients and found 91% of 44 patients had normal ALT levels before their liver was scanned. Of 23 patients who were scanned, 11 (48%) had abnormal findings, and 9 (39%) showed signs of fatty liver. Seven (16%) patients underwent a liver biopsy based on the liver scan findings, and five stopped treatment with MTX based on the findings. Methotrexate also was stopped in nine other patients who did not undergo biopsy but had raised liver stiffness, which is a sign of fibrosis. Meanwhile, three patients continued at a reduced dose.
The patients in their retrospective case note study included those who had undergone FibroScan between 2011 and 2015 while on MTX. Most (56%) patients were taking MTX for RA; 27%, for psoriatic arthritis; 9%, for psoriasis; and the remainder, for other rheumatologic or dermatologic conditions. The median age at the time of the scan was 64 years. Eight patients had comorbid diabetes mellitus, and 11% consumed more than 14 units of alcohol per week.