POS0111 THE LACK OF ASSOCIATION BETWEEN CUMULATIVE METHOTREXATE DOSE AND LIVER FIBROSIS IN PSORIATIC ARTHRITIS: A COHORT STUDY

Background: Several studies have suggested an association between the cumulative methotrexate dose and liver fibrosis in patients with psoriatic disease. However, these studies are primarily derived from the psoriasis literature and many did not account for potential confounding factors. Additionally, some analyses have challenged this association, raising questions about its validity. Objectives: This study aimed to explore the proportion of patients with psoriatic arthritis (PsA) who have liver fibrosis and identify the factors associated with its occurrence, with a particular focus on the cumulative methotrexate dose and metabolic factors. Methods: We analyzed data from a prospective observational cohort of PsA patients. We identified cases of liver fibrosis based on the Aspartate Aminotransferase to Platelet Ratio Index (APRI), a non-invasive marker used to assess liver fibrosis in hepatitis C virus-infected patients and other liver diseases [1–3]. A cutoff of >0.7 was used to denote the presence of liver fibrosis [1]. We performed univariable and multivariable generalized estimating equations (GEE) analysis to model the impact of cumulative methotrexate dose on liver fibrosis. The analysis was adjusted for multiple confounders, including age, sex, PsA duration, calendar time, alcohol consumption (none, socially, and daily), hepatitis (viral, alcohol-induced, drug-induced, and autoimmune), presence of inflammatory bowel disease, human immunodeficiency virus infection, or celiac disease, use of non-steroidal anti-inflammatory drugs, and use of leflunomide or sulfasalazine. Importantly, the analysis also included factors reflective of metabolic-associated steatotic liver disease (MASLD), namely body mass index (BMI), diabetes mellitus, and hyperlipidemia, as well as disease activity and therapy-related variables, including Disease Activity Index for Psoriatic Arthritis (DAPSA) and use of biologic or targeted synthetic disease-modifying anti-rheumatic drugs (DMARDs). Results: A total of 1,314 patients were included in the study, with a mean age of 44.4 (SD 13.1) years and a median disease duration of 2.5 [IQR: 0.7, 8.1] years at baseline (clinic entry) (Table 1). Of these, 375 (28.5%) patients were receiving methotrexate at clinic entry, while 763 (58.1%) had ever received the medication. The median cumulative methotrexate dose of the overall cohort at baseline was 0.0 [IQR: 0.0, 115.0] mg, and for those who had ever taken methotrexate, the median cumulative dose at the last visit was 4696.1 [IQR: 1304.5, 13849.9] mg. Forty (3.3%) of the patients had an abnormal APRI at baseline, indicating liver fibrosis, while 154 (11.7%) developed liver fibrosis during follow-up at a median of 5.6 [IQR: 2.0, 11.1] years from baseline. In the multivariable GEE analysis (Table 2), adjusted for the confounders mentioned above, cumulative methotrexate dose was not independently associated with the occurrence of liver fibrosis (OR 0.99, 95% CI 0.98–1.01). However, higher BMI (OR 1.03, 95% CI 1.00–1.05) and diabetes mellitus (OR 5.03, 95% CI 2.19–11.56) showed a significant association. Conclusion: Liver fibrosis may occur in patients with PsA. Metabolic factors, such as high BMI and diabetes mellitus, rather than the cumulative methotrexate dose, are associated with its occurrence, highlighting the importance of MASLD in PsA. Further studies incorporating imaging are required to confirm our findings. REFERENCES: [1] Lin ZH, Xin YN, Dong QJ, et al. Performance of the aspartate aminotransferase-to-platelet ratio index for the staging of hepatitis C-related fibrosis: an updated meta-analysis. Hepatology. 2011 Mar;53(3):726–36. [2] Loaeza-del-Castillo A, Paz-Pineda F, Oviedo-Cárdenas E, et al. AST to platelet ratio index (APRI) for the noninvasive evaluation of liver fibrosis. Ann Hepatol. 2008;7(4):350–7. [3] Rigor J, Diegues A, Presa J, et al. Noninvasive fibrosis tools in NAFLD: validation of APRI, BARD, FIB-4, NAFLD fibrosis score, and Hepamet fibrosis score in a Portuguese population. Postgrad Med. 2022 May;134(4):435–40. Table 1Patient characteristics at the time of clinic entryVariableOverall(n=1314)Never had liver fibrosis*(n=1116)Ever had liver fibrosis(n=198)Age in years, mean (SD)44.4 (13.1)44.4 (13.3)44.5 (12.4)Sex (male), n (%)742 (56.5)610 (54.7)132 (66.7)Duration of PsA in years, median [IQR]2.5 [0.7, 8.1]2.54 [0.7, 8.2]2.4 [0.8, 8.0]BMI in kg/m2, mean (SD)28.8 (6.3)28.8 (6.4)28.9 (6.1)Alcohol consumption, n (%)None468 (41.0)392 (41.1)76 (40.4)Socially570 (49.9)485 (50.8)85 (45.2)Daily104 (9.1)77 (8.1)27 (14.4)Diabetes mellitus, n (%)83 (6.6)63 (5.9)20 (10.2)Hypertension, n (%)191 (14.6)154 (13.8)37 (18.7)Hyperlipidemia, n (%)98 (8.0)81 (7.9)17 (8.8)Hepatitis~, n (%)31 (2.9)19 (2.2)12 (6.7)DAPSA, median [IQR]16.6 [9.0, 29.2]16.6 [9.0, 30.8]16.0 [9.0, 27.0]Modified Steinbrocker score, median [IQR]2.0 [0.0, 8.0]2.0 [0.0, 8.0]2.0 [0.0, 9.0]Sacroiliitis, n (%)267 (21.7)230 (22.1)37 (19.5)APRI, median [IQR]0.22 [0.16, 0.30]0.21 [0.15, 0.28]0.31 [0.21, 0.60]NSAIDs, n (%)860 (65.4)723 (64.8)137 (69.2)Leflunomide or Sulfasalazine, n (%)100 (7.6)85 (7.6)15 (7.6)Methotrexate, n (%)375 (28.5)324 (29.0)51 (25.8)Cumulative methotrexate dose in mg, median [IQR]0.0 [0.0, 115.0]0.0 [0.0, 133.1]0.0 [0.0, 57.1]Biologic or targeted synthetic DMARDs, n (%)88 (6.7)80 (7.2)8 (4.0)SD, standard deviation; PsA, psoriatic arthritis; IQR, interquartile range; BMI, body mass index; DAPSA, Disease Activity Index for Psoriatic Arthritis; APRI, Aspartate Aminotransferase to Platelet Ratio Index; NSAIDs: Non-steroidal anti-inflammatory drug; DMARDs: disease-modifying anti-rheumatic drugs*Liver fibrosis was defined as an APRI value greater than 0.7~Viral, alcohol-induced, drug-induced, or autoimmune Acknowledgements: NIL . Disclosure of Interests: Fadi Kharouf: None declared, Pankti Mehta: None declared, Virginia Carrizo Abarza: None declared, Shangyi Gao: None declared, Daniel Periera: None declared, Dafna D. Gladman AstraZeneca, Abbvie, Amgen, BMS, Eli Lilly, GSK, Janssen, Novartis, Pfizer, UCB, Abbvie, Amgen, Eli Lilly, Janssen, Novartis, Pfizzer, UCB, Denis Poddubnyy AbbVie, Canon, DKSH, Eli Lilly, Janssen, MSD, Medscape, Novartis, Peervoice, Pfizer, and UCB, AbbVie, Biocad, Bristol-Myers Squibb, Eli Lilly, Janssen, Moonlake, Novartis, Pfizer, and UCB, AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, UCB, Vinod Chandran AbbVie, BMS, Eli Lilly, Fresenius Kabi, Johnson and Johnson, Novartis, UCB, AbbVie, Eli Lilly. © The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.

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