Pos0533 repurposing Fib-4 Score in Rheumatoid Arthritis: Data From the Espoir Cohort

Abstract

BackgroundThe Fibrosis-4 (FIB4) score, including age, transaminases and platelets, can detect severe fibrosis (F3-F4) in patients with Non Alcoolic Steato Hepatitis (NASH) and could be of interest in the follow-up of patients with RA. Indeed, platelets contribute to the pathophysiology of RA, transaminases are used in the liver monitoring of our treatments. In addition, retrospective data suggested the association between FIB4 and mortality in RA (1).ObjectivesWe aimed to evaluate the value of the FIB4 score as a prognostic factor in RA in the prospective ESPOIR cohort.MethodsPatients of the ESPOIR cohort diagnosed with RA according to ACR-EULAR criteria were included in our analysis. The formula for the FIB-4 score is as follows: [Age (years) × ASAT (U/L)] / [Platelet count (10^9/L) × ALT (U/L)1/2]. The analyses were based on linear mixed-effects models with a random effect on the subject to account for repeated measures throughout time.Results633 of the 813 patients included met the ACR/EULAR criteria for RA and had a calculable FIB4 score. Median FIB4 was 0.75 IQR (0.53-0.99) and 61 patients (9.6%) had a high FIB4 score at baseline. Baseline FIB4 was significantly higher in patients with a chronic alcohol consumption (p=0.021) or viral hepatitis (p<0.001). In multivariate analysis, including the main baseline prognostic factors for progression of RA (swollen Joint Count, CRP, Presence of ACPA, Rheumatoid Factor and modified Sharp score), FIB4 was not independently associated with progression of DAS28 during 10 years of follow-up, unlike baseline CRP and SJC. Baseline FIB4 was not associated with the modified Sharp score at 10-year follow-up unlike age and the presence of ACPA (Table 1). FIB4 was not associated with mortality (p=0.77) or major adverse cardiovascular events (p=0.22) during the 10-year follow-up. No significant change in FIB4 score over time was related to the use of NSAIDs, methotrexate, tocilizumab or other DMARDs.Table 1.Associations of FIB4 score with DAS28 and modified Sharp score evolutions in multivariate analysesVariableVariables included in modelp-valueDAS28Time<0.0001Age0.97Baseline number of swollen joints<0.0001Baseline Rheumatoid Factor0.51evolution over timeBaseline ACPA (presence)0.97Baseline CRP<0.0001Baseline modified Sharp score > 00.15Baseline FIB40.26Modified Sharp scoreTime0.052Age0.0005Baseline number of swollen joints0.38Baseline Rheumatoid Factor0.61evolution over timeBaseline ACPA (presence)0.012Baseline CRP0.84Baseline FIB40.25ConclusionOur study was the first to evaluate the value of FIB4 in a prospective cohort of RA patients. The present prospective cohort study with a 10-year follow-up did not find a prognostic role of FIB4 in RA, in contrast to previous retrospective studies. Reassuringly, FIB4 score was not increased by DMARD treatment after 10 years of follow-up, confirming the absence of long-term DMARD-related hepatotoxicity.References[1]Seung Up Kim, Beom Kyung Kim, Jun Yong Park, Do Young Kim, Sang Hoon Ahn, Yong-Beom Park, Kwang-Hyub Han & Sang-Won Lee (2018): Fibrosis-4 index at diagnosis can predict all-cause mortality in patients with rheumatoid arthritis: A retrospective monocentric study, Modern Rheumatology, DOI: 10.1080/14397595.2018.1558760Figure 1.Impact of baseline FIB4 score on DAS28, HAQ and total modified-Sharp score over time.AcknowledgementsAn unrestricted grant from Merck Sharp and Dohme (MSD) was allocated for the first 5 years. Two additional grants from INSERM were obtained to support part of the biological database. The French Society of Rheumatology, Pfizer, Abbvie, Lilly, Sanofi also supported the ESPOIR cohort study.We also wish to thank Nathalie Rincheval (CHU Montpellier and EA 2415) who did expert monitoring and data management and all the investigators who recruited and followed the patients (F. Berenbaum, Paris-Saint Antoine, MC. Boissier, Paris-Bobigny, A. Cantagrel, Toulouse, B. Combe, Montpellier, M. Dougados, Paris-Cochin, P. Fardellone et P. Boumier Amiens, B. Fautrel, Paris-La Pitié, RM. Flipo, Lille, Ph. Goupille, Tours, F. Liote, Paris- Lariboisière, O. Vittecoq, Rouen, X. Mariette, Paris Bicetre, P. Dieude, Paris Bichat, A. Saraux, Brest, T. Schaeverbeke, Bordeaux, J. Sibilia, Strasbourg) V. Devauchelle and C Lukas for expert X-ray reading.Disclosure of InterestsNone declared.