AB0649 B CELL DEPLETION THERAPY IN VERY EARLY SYSTEMIC SCLEROSIS. A POTENTIAL WINDOW OF OPPORTUNITY?

Abstract

Background Our group, among others, has shown that B cell depletion therapy may improve skin thickening and interstitial lung disease (ILD) related to systemic sclerosis (SSc). All studies assessing the clinical efficacy of B cell depletion therapy in SSc have recruited patients with established disease fulfilling the old classification criteria. In our previous studies we have found that patients with shorter disease duration had a better clinical response to RTX. Objectives It is unknown whether treatment in very early SSc can affect long term outcomes. We aimed at assessing the effect of rituximab (RTX) in patients with very early SSc. Methods We report 2 cases where RTX was administered within 24 months from the appearance of Raynaud’s. Results A 56 year-year-old female with an 18-month history of Raynaud’s developed interstitial lung disease (ILD) with extensive ground glass lesions, a normal FVC (82%) but decreased DLco (44%). A diagnosis of SSc was made based on the presence of positive anti-centromere antibodies, puffy fingers, telangiectasias, positive capillaroscopy, ILD and Raynaud’s. Six months following RTX treatment, her PFT’s had increased (FVC 94% and DLco 55%) and chest HRCT showed an obvious improvement. One year later the patient no longer reported dyspnea. She remained on RTX for 5 years with no respiratory symptoms, stable PFTs and no evidence of disease progression. The second case is a 27-year old female with a 1-year history of Raynaud’s, puffy fingers, positive anti-Scl70 and capillaroscopy. Within a few months her skin thickened rapidly reaching an MRSS of 12 and developed tendon friction rubs. Six months following RTX treatment skin thickening had almost resolved; she only had mild sclerodactyly. Tendon friction rubs disappeared. The patient received 8 consecutive RTX courses throughout a period of 4 years. During this period the patient remained in a steady clinical condition with no signs of disease progression. Conclusion It is generally accepted that autoimmunity/immune dysregulation and vasculopathy are the primary events in SSc that eventually trigger the fibrotic process. Based on this pathogenetic model, one can hypothesize that a therapeutic intervention very early in the disease course, prior to the appearance of fibrotic manifestations could potentially prevent permanent organ damage. Our data suggest that there may be a window of opportunity in SSc. This is why we propose that large scale, controlled studies assessing the efficacy of RTX (or other immune based therapies such as mycophenolate) in patients with very early disease are highly needed. Disclosure of interests None declared