Background/Purpose: Methotrexate (MTX) is the first-line treatment in Rheumatoid arthritis (RA) patients. To date, the evidence about the liver disease caused by MTX is controversial. Often, cardiovascular (CV) risk factors such as arterial hypertension, dyslipidemia, obesity, and insulin resistance are accompanied by liver abnormalities suggesting an interplay of CV disease and hepatic dysfunction.
Objective: To analyze the impact of MTX on liver enzymes, hepatic indexes, and disease activity after six months of treatment taking into account cardiovascular comorbidities in early RA patients.

Methods: Fifty newly diagnosed RA patients treated with MTX were included in a longitudinal study. Clinical parameters, classical liver disease biomarkers and hepatic steatosis predictor (hepatic steatosis index (HSI)) and fibrosis (fibrosis 4 score (FIB-4), and aspartate aminotransferase to platelet ratio index (APRI)) predictors were analyzed at baseline and after 6 months of treatment. CV disease comorbidities such as arterial hypertension (ATH), type 2 diabetes mellitus (T2DM), obesity, and smoking habit were also analyzed at baseline classifying RA patients into three groups: group with none comorbidities (_com) (group =0_com), group with 1 comorbidity (group =1_com) and group with more than 1 comorbidity (group >1_com). According to EULAR response criteria, RA patients were divided into good, moderate, and non-responders. Paired t-tests were used to test differences between pairs’ measurements.

Results: RA patients from group >1_com were characterized by a significantly high prevalence of ATH and T2DM, higher rates of obesity, and lower smokers compared to the group=1_com. Interestingly, RA patients with no comorbidities did not present any alterations in transaminases and hepatic steatosis and fibrosis predictors after 6 months of treatment. In contrast, RA patients from group >1_com showed significantly elevated levels of transaminases and HSI, APRI and FIB-4 after the treatment suggesting the potential deleterious effect of MTX in the liver of patients with higher rates of CV disease. The disease activity was significantly reduced in the three groups, however, the reduction was lower in the group >1_com (mean difference of DAS28= -2.255) compared to group 1_com (mean difference of -2.670) and group=0_com (mean difference of -2.846). In this line, RA patients from group=0_com showed the highest rate of good response (92.9%) followed by group 1_com (88.2%) and group >1_com (54.5%). Also, RA non-responder patients showed significantly elevated levels of HSI at baseline and after 6 months of treatment compared to good responders suggesting its potential role as a marker of therapeutic response.

Conclusion: The treatment with MTX for 6 months promotes liver abnormalities in newly-diagnosed RA patients having more than one cardiometabolic comorbidity, accompanied by a less reduction of the disease activity.

Funded by ISCIII (PI20/00079) and MINECO (RyC-23437).

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/effects-of-methotrexate-on-the-liver-function-and-disease-activity-of-newly-diagnosed-ra-patients-depending-on-the-cardiometabolic-profile/