Rheumatoid arthritis

Leading rheumatologists dispute MTX alcohol advice


Rheumatologists in the US have slammed a widely reported UK study that claimed moderate levels of drinking is safe for patients with RA on methotrexate, calling the research disappointing and misleading.

The retrospective observational study based on medical records of almost 12,000 people with rheumatoid arthritis concluded that patients taking the immunosuppressant were not at increased risk of transaminitis if they stuck to 14 units of alcohol a week or fewer.

According to the UK investigators, led by Dr William Dixon from the University of Manchester, patients who consumed between 15-21 units a week had a 33% increased probability of transaminitis – a risk that increased to 81% in the group that drank more than 21 units.

The researchers said that including these ‘acceptable’ alcohol levels in clinical guidelines could improve decision-making, clinical outcomes and overall quality of life for patients.

But rheumatologists Dr Joel Kremer and Dr Michael Weinblatt have been critical of the study warning doctors that the UK investigators’ threshold for hepatotoxicity – alanine transaminase or aspartate aminotransferase at least three times the upper limit of normal – was too high and likely to miss many patients at risk for hepatic fibrosis or cirrhosis.

In a cutting letter to the editor of the Annals of the Rheumatic Diseases the US physicians, who have been involved in researching liver toxicity in RA patients on MTX since the 80’s, argue that there are in fact no liver biopsies or hepatic scans that have been reported to establish the validity of transaminitis as meaningful indicator of liver disease in patients with RA receiving long term MTX.

They also claim that the number of liver function tests patient were required to have in order to be included in the study – a minimum of six – were inadequate to pick up an established pattern of transaminitis.

They maintain that any claims of safe drinking levels based on the UK paper are ‘misleading’.

“We are not quite as sanguine about their recommendations for alcohol use since their definition of liver toxicity is rather arbitrary and not consistent with data that have been derived over several decades of prospective study with actual hepatic tissue from annual biopsy specimens,” the US specialists wrote.

But responding swiftly just days later Dr Dixon defended his study claiming it reflects ‘real-life’ usage versus a ‘carefully monitored research cohort’.

In his reply, he argued that while transaminitis might well be an arbitrary indicator of liver damage it was one that had an established link in patients with rheumatoid arthritis being treated with MTX and was an indicator that could be used to provide practical evidence to guide patients about safe drinking levels – an area that is seriously lacking.

“Setting a clinically important increase will always be arbitrary, but allowed us to provide further information beyond the traditional statistical tests,” he wrote.

He said the study adds information that was previously unavailable to clinicians and would help address a question that is frequently asked by patients – whether alcohol may be consumed while taking MTX.

“Our data do not mean that it is completely safe to drink up to 14 units of alcohol per week, merely that in terms of the outcome of transaminitis per our two definitions, we saw no evidence of an increased risk.

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