Antirheumatic Drugs May Impact Risk of NAFLD in Patients with Rheumatoid Arthritis, Study Finds

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Nonsteroidal anti-inflammatory drug use and prednisolone equivalent dose > 5 mg per day are associated with an increased risk of nonalcoholic fatty liver disease (NAFLD) in patients with rheumatoid arthritis (RA), according to findings from a population-based cohort study in Taiwan.

Results also showed a decreased risk of NAFLD among those using hydroxychloroquine and prednisolone equivalent dose ≤5 mg per day, further detailing the impact of a history of hospitalizations, number of outpatient visits, age, gender, and leflunomide use on the development of NAFLD in certain patient subgroups.¹

“Shared mechanisms have been identified between RA and NAFLD, including the involvement of pathogenic cytokines such as tumor necrosis factor (TNF)-α13 and IL-6. It is posited that biologics targeting these cytokines could potentially reduce the prevalence of NAFLD,” wrote investigators.¹ “Yet, there remains an absence of large-scale studies comprehensively evaluating the influence of prevalent antirheumatic drugs on NAFLD risk among RA patients.”

A chronic disease causing bodily inflammation, RA commonly presents with pain in the joints and can lead to severe joint damage as well as heart, lung, or nervous system complications. According to the World Health Organization, 18 million people worldwide were living with RA in 2019.2 Although shared mechanisms between RA and NAFLD have previously been identified and led to speculation regarding the impact of antirheumatic drugs on disease risk, little research has comprehensively explored this potential association.¹

To assess the association between antirheumatic drugs and the risk of NAFLD in patients with RA, Chia-Chu Meng, of the division of allergy, immunology, and rheumatology at Taichung Veterans General Hospital in Taiwan, and colleagues used claim data from the Taiwanese National Health Insurance Research Database and the Catastrophic Illness Registry to identify patients with newly diagnosed RA between 2002 and 2020 and examine for an eventual NAFLD diagnosis.¹

An initial 41,791 patients were identified based on registration in the Catastrophic Illness Registry of the National Health Insurance Research Database for a diagnosis of RA. After applying exclusion criteria for having a diagnosis of acute/subacute necrosis of the liver, chronic liver disease, alcoholic liver disease, liver abscess/sequelae of chronic liver disease, hepatitis B, hepatitis C, alcohol-related disorders, and missing data for residence or insurance, the remaining 21,457 patients were included in the study.¹

The study's primary outcome was time from the index date to the initial outpatient or ambulatory visit where a NAFLD diagnosis was recorded. Participants were classified as having NAFLD if they had at least 1 hospitalization or made 3 outpatient visits with a corresponding diagnosis of NAFLD. Investigators identified age, gender, level of insured amount, level of urbanization, medical utilization, and selected comorbidities including diabetes mellitus, infection, and obesity-related comorbidities as potential confounders to account for in statistical analyses.¹

Among the cohort (n = 21,457), the median age was 52 (Interquartile range, 42.0-61.0) years and 76.3% of participants were female. Nearly all (99.6%) participants were prescribed non-steroidal anti-inflammatory drugs - 94.1% took steroids and 10.9% used urate-lowering therapy. The most frequently used medications were steroids (94.1%), methotrexate (84.5%), hydroxychloroquine (87.5%), and sulfasalazine (71.7%).¹

During follow-up, 399 (1.86%) participants developed NAFLD, with an incidence rate of 221 (per 10−5 person-years). Investigators noted multivariable time-dependent Cox regression analyses showed defined daily dose of non-steroidal anti-inflammatory drugs (Adjusted hazard ratio [aHR], 1.03; 95% Confidence interval, 1.02–1.05) and prednisolone equivalent dose >5 mg/day (aHR, 2.39; 95% CI, 1.85–3.09) were significant predictors for the risk of NAFLD. However, they also pointed out use of hydroxychloroquine (aHR, 0.75; 95% CI, 0.60–0.93) and prednisolone equivalent dose ≤5 mg/day (aHR, 0.53; 95% CI, 0.40–0.71) were associated with a decreased risk of NAFLD. A history of hospitalizations, number of outpatient visits, age, gender, and leflunomide use were associated with the development of NAFLD in some subgroups.¹

“Our study may facilitate more detailed recommendations of medications for the prevention of NAFLD in patients with RA, and encourage more researchers to investigate related issues in the future,” investigators concluded.¹

References:

1. Meng CC, Chen DY, Chen YH, et al. Antirheumatic drugs and the risk of nonalcoholic fatty liver disease in patients with rheumatoid arthritis: A nationwide, population-based cohort study. Int J Rheum Dis. 2023;00:1–13. doi:10.1111/1756-185X.15003.
2. World Health Organization. Rheumatoid arthritis. Newsroom. June 28, 2023. Accessed December 12, 2023. https://www.who.int/news-room/fact-sheets/detail/rheumatoid-arthritis