AB0414 THE IN VITRO EFFECT OF BIOLOGICAL AND CONVENTIONAL DISEASE MODIFYING ANTI RHEUMATIC DRUGS (DMARDS) ON FIBROCYTE DIFFERENTIATION IN RHEUMATOID ARTHRITIS PATIENTS AND HEALTHY CONTROLS
Authors: Helene Tenstad, Pernille Just Vinholt, Christian Nielsen, Hanne Merete Lindegaard, Søren Andreas Just
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Fibrocytes are circulating cells with both myeloid and haemopoietic properties. They home in tissues with active inflammation, where they differentiate into mature fibrocytes that are involved in several inflammatory pathways. One complication of Rheumatoid Arthritis (RA) is Interstitial Lung Disease (ILD) resulting in high mortality and with limited treatment options. Fibrocyte levels are elevated in RA patients compared with healthy individuals and further increased in RA patients with signs of ILD (reduced diffusion capacity) and in patients with idiopathic lung fibrosis (IPF) or scleroderma. Thus, fibrocytes have been proposed as a future treatment target. <h3>Objectives</h3> We investigate the effect of corticosteroids, conventional Disease Modifying Anti Rheumatic Drugs (cDMARDs) and biological DMARDs (bDMARDs) on the <i>in vitro</i> differentiation of isolated peripheral blood mononuclear cells (PBMCs) into mature fibrocytes. <h3>Methods</h3> 10 participants were included<b> (</b>five patients with RA and five healthy controls). Information on current medication, sex, age, serology and disease activity were collected. PBMCS were isolated and cultured for 5 days in four wells per drug. Drugs included prednisolone, cDMARD (Methotrexate, Sulfasalasine, Hydroxycloroquine) and bDMARD (Inflectra, Etanecept, Tocilizumab, Adalimumab, Abatacept, Rituximab), and control wells with no drugs. <h3>Results</h3> Overall, abatacept and prednisolone significantly suppressed differentiation of PBMC into fibrocytes compared to control wells, see Figure 1 (p=0.02 and p&lt;0.01, respectively) (n=10). The reductive effect of Abatacept was significant among RA patients (p=0.009 and) but not among healthy subjects. In overall analysis (n=10), Abatacept reduced fibrocyte levels with an average of 44% overall and in the RA group 71% compared to control wells. Tocilizumab reduced the fibrocyte count with 63% overall and 45% in the RA group, although not significant (p=0.07 and p=0.06 respectively). <h3>Conclusion</h3> Abatacept and prednisolon suppress the differentiation of mononuclear cells to mature fibrocytes <i>in vitro</i> in RA patients and data indicating a similar effect of Tocilizumab. Prednisolone are used in the treatment of RA-ILD but has a marked toxicity, so new treatment modalities are desirable. Our findings are in line with the fact that fibrocytes have the receptors targeted by abatacept, furthermore recent scleroderma research has shown Abatacept to reduce fibrocyte levels <i>in vitro</i> and Tocilizumab to potentially reduce lung and skin affection( 1, 2) Further research using abatacept and tocilizumab to target fibrocytes are needed in order investigate the treatment potential of these drugs in RA-ILD. Ledgend: Demonstrates the different medical agents used and the number of cultured fibrocytes counted after 5 days of incubation. Values are mean +/- SEM. ** indicates statistical significance compared with the control well by ANOVA compared to the control (p&lt;0.05) <h3>References</h3> [1] Cutolo M, et al. Effects of CTLA4-Ig treatment on circulating fibrocytes and skin fibroblasts from the same systemic sclerosis patients: an in vitro assay. Arthritis Research &amp; Therapy. 2018;20. [2] Khanna D, et al. Safety and efficacy of subcutaneous tocilizumab in systemic sclerosis: results from the open-label period of a phase II randomised controlled trial (faSScinate). Ann Rheum Dis. 2018;77(2):212-20. <h3>Disclosure of Interests</h3> None declared