SAT0477 Intensified b-cell depletion therapy in progressive systemic sclerosispatients: 24 months follow-up
Authors: D. Rossi, I. Cecchi, S. Sciascia, M. Radin, E. Rubini, D. Roccatello
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Systemic sclerosis (SSc) is a connective tissue autoimmune disease with systemic involvement and a serious medical condition with a high rate of mortality, especially due to interstitial lung disease (ILD).The exact pathophysiology is still unclear, but B cells seem to play a crucial role in the initiation and the progression of the disorder.<sup>1</sup> Therefore, the use of Rituximab (RTX) might have a rational in the treatment of SSc. <h3>Objectives</h3> We aimed to investigate the outcomes of SSc patients treated with RTX after a follow-up of 24 months. <h3>Methods</h3> We retrospectively collected data from SSc patients<sup>2</sup> resistant or intolerant to previous therapies, treated with intensified B-depletion therapy, between 2013 and 2016. Therapeutic protocol comprehends: RTX 375 mg/sm on days 1, 8, 15, 22, and two more doses after one and two months, associated with two intravenous administrations of 10 mg/kg of cyclophosphamide and three methylprednisolone pulses (15 mg/kg) followed by oral prednisone (0.8 mg/kg/day, rapidly tapered to 5 mg/day by the end of the 3rd month after RTX). <h3>Results</h3> he study included 20 SSc patients (18 females and 2 males; mean age 66.7±11.0 years). Patients presented with severe multiorgan involvement: ILD (19/20, 95%), pulmonary hypertension (12/20, 60%), and skin thickening (17/20, 85%). After a follow-up of 24 months, we observed a decrease in the levels of NT-proBNP (mean baseline: 385.4±517, mean at 24 months: 283±648, p&lt;0.05), and in the Modified Rodnan Skin Score (mRSS) (mean mRSS baseline: 14.4±10.5, mean after 24 months of follow-up: 12.9±10, p&lt;0.05). Four out 19 (21%) patients experienced a significant improvement of ILD, as assessed by high-resolution computed tomography, while in 12/19 (63%) patients the intensified B-cell depletion therapy was associated with a stabilisation of the imaging features with no sign of progression. Three out of 19 (16%) patients showed a deterioration of the ILD. Patients showed no significant decrease in forced vital capacity (FVC) (mean baseline FVC: 93.6±19.3, mean after 24 months of follow-up: 92.2±23.3), no significant decrease in forced expiratory volume in one second (FEV1) (mean baseline FEV1: 89.5±15.6, mean FEV1 at 24 months: 87±21.2), no significant decrease in diffusing capacity (DLCO) (mean baseline DLCO values: 58.8±8.6, mean at 24 months: 60.3±14), no significant change in the ejection fraction (EF) (mean baseline EF values: 62.8±6.4, mean EF values at 24 months: 58.6±7.1) and in pulmonary artery pressure (PAP) (mean baseline PAP: 30.2±10.5, mean at 24 months: 31.1±11.05). <h3>Conclusions</h3> Despite recent advances in the treatment of SSc, ILD heavily affects prognosis and life expectancy of these patients. Our data suggest that the intensified B-depletion therapy protocol might represent a promising tool for the management of SSc in terms of controlling the progression of the disease, especially when considering pulmonary and skin manifestations. Further prospective studies are needed in order to confirm our results. <h3>References</h3> [1] Forestier A, Guerrier T, Jouvray M, Giovannelli J, Lefèvre G, Sobanski V, et al. Altered B lymphocyte homeostasis and functions in systemic sclerosis. Autoimmun Rev2018. [2] Pope JE, Johnson SR. New Classification Criteria for Systemic Sclerosis (Scleroderma). Rheum Dis Clin North Am2015;41:383–98. <h3>Disclosure of Interest</h3> None declared