Rituximab in the treatment of refractory pulmonary sarcoidosis

Abstract

To the Editor: Sarcoidosis is a chronic disease characterised by granulomatous depositions that can occur in virtually any organ system [1]. Currently, there is no US Food and Drug Administration (FDA)-approved therapy for sarcoidosis; however, corticosteroids have proven efficacious and are a commonly used treatment [2]. In patients with chronic or pulmonary disease who do not respond to corticosteroids, or in whom steroid use is contraindicated, agents such as methotrexate, azathioprine and tumour necrosis factor (TNF)-α antagonists may be effective [3, 4]. However, a need persists for patients who fail to respond to current options. Sarcoidosis is a T-cell-mediated disease; however, humoral mechanisms may play a role in its pathogenesis [5]. Sarcoidosis is often associated with hypergammaglobulinaemia, autoantibody production and circulating immune complexes [6]. B-cell-targeted therapies have shown positive results in many T-cell-mediated autoimmune diseases. Rituximab is a chimeric monoclonal antibody that causes depletion of CD20+ B-cells [7]. Rituximab is FDA approved for the treatment of rheumatoid arthritis, granulomatosis with polyangiitis (Wegener’s) and microscopic polyangiitis, and is also being studied in Sjogren’s syndrome, systemic lupus erythematosus and vasculitis [8]. There have been case reports of the effectiveness of rituximab for sarcoidosis [9–11]. Given the evidence for humoral involvement in sarcoidosis pathogenesis, this study sought to evaluate the utility of B-cell depletion using rituximab in patients with refractory pulmonary sarcoidosis. This was a prospective, open-label, phase I/II trial. The study was approved by the …