EFFECT OF TOFACITINIB IN TREG /TH17 BALANCE IN RHEUMATOID ARTHRITIS

Background: Rheumatoid arthritis (RA) is a systemic chronic autoimmune disease that can cause progressive articular destruction (1). The imbalance between Tregs and Th17-cells - an effector T-cell subset acting as Treg antagonists – is closely linked to autoimmunity (2). A shift in the Th17/Treg balance towards the pro-inflammatory Th17 side has been reported in many autoimmune disorders including RA (4-5). Tofacitinib is the first janus kinases (JAK) inhibitor (JAKi) approved for the treatment of RA and it binds to and competitively inhibits the kinase domain of JAK3, JAK1 and, to a lesser degree, JAK2. Data on JAKi and Th17 cells/regulatory T cells (Tregs) are only available for ruxolitinib, a JAKi registered for myeloproliferative diseases (6). Objectives: Our project aimed at investigate the possible effect of Tofacitinib on the Treg/Th17 balance in RA patients. Methods: We isolated Peripheral Blood Mononuclear Cells (PBMCs) from patients affected by RA at baseline (T0) and after one month of Tofacitinib therapy (T1). By flow cytometry we characterized Treg and Th17 at T0 and T1. Clinical and laboratory data of the patients were collected in a standardized, computerized and electronically filled form. We assessed the disease activity by using DAS-28 (CRP). Data were expressed as mean(SD) or median (interquartile range, IQR) according to the variables’ distribution. Mann-Whitney and Spearman test were used. The values of P Results: We isolated PBMCs from 9 patients with RA (F:M = 7:2, mean age±SD 60±17.4 years; mean disease duration±SD 20±6.6 years, DAS-28 median at T0 4.14 IQR 1.6; at T1 3.08 IQR 1.3). The median percentage of Treg and Th17 at T0 and T1 were respectively: T0 1.85 IQR 0.98 T1 3.12 IQR 1.37; T0 1.64 IQR 1.4, T1 0.6 IQR 1.1. Treg significantly increased after tofacitinib treatment while Th17 showed a tendency in decreasing without achieving a statistical difference (p= 0.003 and p=0.8, respectively) (figure 1). DAS-28 was negatively correlated with Treg number (r = -0.76565, p = 0.00021) and positively with Th17 numbers (r = 0.5816, p = 0.01135). Conclusion: This is the first study that investigated the role of JAKi on the Treg/Th17 balance in RA showing and increase in Treg cells with a concurrent tendency in decrease of Th17 cell population. The restore of the Treg/Th17 balance was associated with the reduction of DAS-28 (CRP). References: [1]McInnes IB et al. Lancet 2017 [2]Fasching P et al. Molecules 2017 [3]Han L et al. Front. Med. 2015 [4]Beringer A et al. Med. 2016 [5]Lippert E et al. Blood 2006 Disclosure of Interests: viviana antonella pacucci: None declared, cristiana barbati: None declared, Francesca Romana Spinelli Grant/research support from: Pfizer, Speakers bureau: Lilly, BMS, Celgene, Fulvia Ceccarelli: None declared, Silvia Mancuso: None declared, Cristina Garufi: None declared, cristiano alessandri Grant/research support from: Pfizer, fabrizio conti Speakers bureau: BMS, Lilly, Abbvie, Pfizer, Sanofi