Reuters Health Information: Moderate alcohol use could be safe with methotrexate for RA
Moderate alcohol use could be safe with methotrexate for RA
Last Updated: 2017-04-12
By Scott Baltic
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
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
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
�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
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.
Ann Rheum Dis 2017.