Single‐dose versus low‐dose rituximab in corticosteroid‐resistant or relapsed ITP: A multicenter, randomized, controlled study

Abstract

Primary immune thrombocytopenia (ITP) is an autoimmune bleeding disorder, in which rituximab (RTX) induces the best long-term effect among recommended second-line treatments. Nevertheless, the optimal regimen of RTX remains unclear. We herein conducted a prospective, multicenter, open-label, randomized controlled trial to compare the efficacy and safety of RTX at two different dosage regimens in patients with corticosteroid-resistant or relapsed ITP. Recruited patients were randomly assigned (1:1) to receive either RTX at a repeated low dose (100 mg weekly for 4 weeks, LD-RTX) or at a single dose (375 mg/m 2 , S-RTX). Overall response was achieved in 64.3% of patients who received LD-RTX versus 67.4% of those receiving S-RTX (p = .759). The complete response (CR) rate was 23.8% after LD-RTX and 28.3% after S-RTX (p = .635). In health-related quality of life, S-RTX improved patients' psychological status, quality of life, social activities, and work compared with LD-RTX. Furthermore, S-RTX significantly reduced physician visits without compromising efficacy. Our findings demonstrate that a S-RTX is comparable to LD-RTX in effectiveness and safety for treatment of corticosteroid-resistant or relapsed ITP. The single-dosage regimen optimizes the use of medical resources, improves the cost-effectiveness of RTX, and represents a promising and more convenient replacement for LD-RTX in ITP. This study has been completed and is registered with ClinicalTrials.gov, number NCT03258866. | INTRODUCTIONPrimary immune thrombocytopenia (ITP) is an acquired immune-mediated disorder in which both increased platelet destruction and impaired platelet production result in low platelet counts, an increased risk of bleeding, and a diminished health-related quality of life (HRQoL). [1][2][3][4][5] It is mainly caused by pathological antiplatelet autoantibodies, T-cell abnormality, and impaired megakaryocyte generation. The standard initial treatments include corticosteroids and intravenous immunoglobulin 6-8 ; however, unfortunately, only 20%-30% of patients achieve a durable response, while the majority require further therapy. 9,10 Rituximab (RTX) is an anti-CD20 chimeric monoclonal antibody 11 that targets B cells and induces reversible B-cell depletion. RTX is effective in the treatment of ITP and recommended as a second-line treatment

Modeling and affinity maturation of an anti-CD20 nanobody: a comprehensive in-silico investigation

“…CD20 is an adequate target on the cell surface of the B-cells 48 , which could be targeted by mAbs. Rituximab is an approved therapy for patients with NHL that can specifically target B cells and induce reversible B cell depletion 49 .…”

“…CD20 is an adequate target on the cell surface of the B-cells 48 , which could be targeted by mAbs. Rituximab is an approved therapy for patients with NHL that can specifically target B cells and induce reversible B cell depletion 49 . Despite the satisfactory results achieved by rituximab, there are also some reports about the unsuccessful outcomes of this antibody 6 .…”