Efficacy and Safety of Rituximab in Connective Tissue Disease-Associated Thrombotic Thrombocytopenic Purpura/Thrombotic Microangiopathy

Abstract

Introduction

This study examined the efficacy and safety of Rituximab (RTX) treatment in connective tissue disease (CTD)-associated thrombocytopenic purpura (TTP) and thrombotic microangiopathy (TMA), using historical controls as comparators.

Methods

Patients who were admitted to our department from March 1, 2013 to March 31, 2021, and diagnosed with CTD-associated TTP/TMA refractory to plasma exchange were included in the study. A patient with treatment-resistant disease was treated with RTX in addition to high-dose glucocorticoid (GC) therapy (GC + RTX). As historical controls, we selected patients with CTD-associated TTP/TMA who were admitted to our center and treated with GC and immunosuppressants (IS) such as cyclophosphamide. The primary endpoint was the survival rate 52 weeks after the start of treatment.

Results

Fifteen patients were enrolled in the study (GC + RTX). As a control group, 11 patients were enrolled in the same manner (GC + IS). There were no significant differences in age or sex or laboratory tests between the two groups. The primary endpoint of survival rate was significantly higher in the GC + RTX group than in the GC + IS group. In the immunophenotyping analysis before treatment, among all subsets of immune cells, only plasmocytes were significantly elevated in TTP patients compared to healthy controls. Plasmocytes correlated with serum markers, suggesting increased B cell differentiation, which was markedly decreased after RTX treatment.

Conclusion

In CTD-associated TTP/TMA, B cells may affect pathology, and adding RTX to plasma exchange and GC therapy may be worth considering.