ASSOCIATION BETWEEN DISEASE ACTIVITY AND CHANGES IN FIBROSIS-4 INDEX LEVEL IN PATIENTS WITH RHEUMATOID ARTHRITIS TREATED WITH METHOTREXATE FOR A SHORT PERIOD

N. Namura, K. Kamada, T. Hagiwara, K. Takahashi, K. MatsuiHyogo Medical University, Division of Allergology and Rheumatology, Department of Internal Medicine, Nishinomiya, Japan Takarazuka City Hospital, Rheumatology, Takarazuka, Japan Hyogo Medical University, Department of Medical Statistics, Nishinomiya, Japan  Background Liver fibrosis and liver damage are major concerns associated with long-term side effects in patients with rheumatoid arthritis (RA) treated with methotrexate (MTX). Recently, fibrosis-4 index (FIB-4) has often been used as an indicator of liver fibrosis. However, most studies examining the association between MTX and liver fibrosis, including FIB-4, have involved patients with RA treated with MTX for an extended period. To the best of our knowledge, no study has reported associations between FIB-4 and disease activity in patients with RA after using MTX for a short period. Objectives We focused on FIB-4 as an indicator of liver fibrosis in patients with RA treated with MTX in phase I and aimed to evaluate the changes in FIB-4 level in these patients for a short period. Methods Patients diagnosed with RA at our hospital and who had not received MTX before diagnosis (using the 2010 ACR/EULAR criteria) were included. Patients with hepatitis virus infection, alcoholism, or severe obesity were excluded from the study. Patients unable to continue using MTX for more than 12 months and those who used a maximum dose of MTX of 10 mg/week or less during the observation period were excluded. Patients’ clinical and functional data were recorded at baseline and at all subsequent visits (6 and 12 months). We used the Mann–Whitney U test to compare aspartate transaminase (AST), alanine aminotransferase (ALT), and FIB-4 levels between the baseline and each observation period. Multiple regression analysis was performed to examine the effect of the cumulative MTX dose on the changes in FIB-4 levels from baseline to 6 and 12 months, after adjusting for factors involved in RA. Results A total of 144 patients were examined. The median FIB-4 levels increased from baseline to 6 and 12 months (p <.001). Multiple regression analysis revealed that the cumulative MTX dose was not a factor independently influencing the changes in FIB-4 levels. Therefore, to identify predictors other than the cumulative MTX dose for changes in FIB-4 levels from baseline, we performed multiple linear regression analysis, after adjusting for sex, body mass index (BMI), CRP, MMP-3, mHAQ, RF, ACPA, DAS28ESR, and FIB-4 level at baseline, defining the changes in FIB-4 level from baseline as the dependent variable. The factors independently influencing the changes in FIB-4 level were DAS28ESR (β = 0.107) at 6 months and DAS28ESR (β = 0.086) at 12 months. DAS28ESR at baseline affected the changes in FIB-4 level from baseline to both observation periods. There was also a significant correlation between the change in FIB-4 from baseline to each period and the DAS28ESR (p <.001). Further, a mediation analysis was performed for the association between DAS28ESR and the changes in FIB-4 level, considering the cumulative MTX dose as a mediator. The results indicated that the cumulative MTX dose did not mediate the relationship between DAS28ESR at baseline and the changes in FIB-4 level at either observation period. Conclusion The cumulative MTX dose did not affect the changes in FIB-4 level over a short period. In contrast, disease activity in patients with RA before MTX administration showed an effect on the changes in FIB-4 level. Clinicians should be more careful regarding liver fibrosis after MTX administration when treating patients with higher disease activity before treatment. References Int J Rheum Dis, 2019. 22(2): p. 214-221. Mod Rheumatol, 2019. 29(6): p. 936-942. Acknowledgements I would like to thank for Prof. Kiyoshi Matsui and Ms. Kanae Takahashi for collaboration on this research. Disclosure of Interests None Declared. Keywords: Rheumatoid arthritis, Descriptive Studies, Comorbidities DOI: 10.1136/annrheumdis-2023-eular.574Citation: , volume 82, supplement 1, year 2023, page 1340Session: Rheumatoid arthritis - comorbidity and clinical aspects (Publication only)