Quantifying the hepatotoxic risk of alcohol consumption in patients with rheumatoid arthritis taking methotrexate

Abstract

Background: Patients with rheumatoid arthritis (RA) who take methotrexate (MTX) are advised to limit their alcohol intake due to potential combined hepatotoxicity. However, data are limited to support this. The aim of this study was to quantify the risk of developing abnormal liver blood tests at different levels of alcohol consumption, using routinely collected data from primary care.

Methods: Patients with RA in the Clinical Practice Research Datalink starting MTX between 1987 and 2016 were included. Hepatotoxicity was defined as transaminitis: alanine transaminase or aspartate aminotransferase more than three times the upper limit of normal. Crude rates of transaminitis were calculated per 1000 person-years, categorised by weekly alcohol consumption in units. Cox proportional hazard models tested the association between alcohol consumption and transaminitis univariately, then age and gender adjusted.

Results: 11 839 patients were included, with 530 episodes of transaminitis occurring in 47 090 person-years follow-up. Increased weekly alcohol consumption as a continuous variable was associated with increased risk of transaminitis, adjusted HR (95% CI) per unit consumed 1.01 (1.00 to 1.02); consuming between 15 and 21 units was associated with a possible increased risk of hepatotoxicity, while drinking >21 units per week significantly increased rates of transaminitis, adjusted HR (95% CI) 1.85 (1.17 to 2.93).

Conclusions: Weekly alcohol consumption of <14 units per week does not appear to be associated with an increased risk of transaminitis.

Keywords: Epidemiology; Methotrexate; Rheumatoid Arthritis; Treatment.

Figure 1

Flow chart of patients included and excluded from the study of the patients with only alcohol status recorded and no weekly units; those who reported drinking no alcohol (1770) were subsequently recorded as drinking zero units per week and were then included in the final model. CPRD, Clinical Practice Research Datalink; LFT, liver function test; MTX, methotrexate; RA, rheumatoid arthritis.

Figure 2

Posterior probabilities of the hazard function. The area under each curve (AUC) represents the probability of the hazard function at that rate of alcohol consumption. The dotted line denotes an arbitrary clinically significant increase in risk of transaminitis of 50% (which would represent an increase in the crude rate from 12 to 18 per 1000 person-years). The AUC to the right of the dotted line is the probability that the hazard function is greater than the clinically significant margin.