Rituximab therapy for thrombotic thrombocytopenic purpura: A proposed study of the Transfusion Medicine/Hemostasis Clinical Trials Network with a systematic review of rituximab therapy for immune‐mediated disorders

Abstract

The rationale for immunosuppressive therapy of thrombotic thrombocytopenic purpura (TTP) was established by observations that TTP may be caused by autoantibodies to ADAMTS13. Patients with high-titer autoantibodies to ADAMTS13 may have a higher mortality, and survivors may require prolonged plasma exchange therapy in spite of adjunctive glucocorticoid treatment. More intensive immunosuppressive therapy with rituximab may provide benefit for many of these patients. The Transfusion Medicine/Hemostasis Clinical Trials Network is developing a randomized, clinical trial to test the hypothesis that addition of rituximab to standard treatment of TTP with plasma exchange and glucocorticoids will decrease initial treatment failure rates as well as subsequent relapses over the following 3 years. To provide the background data for this clinical trial, a systematic review of all published reports on rituximab treatment of immune-mediated disorders was performed. Twelve articles have reported 27 patients treated with rituximab for TTP, with benefit described in 25 (93%) of the patients. Additional reports have described rituximab treatment of 37 other immune-mediated disorders, with clinical response in most patients. These observations from small uncontrolled case series provide the background and rationale for a randomized clinical trial to establish the role of rituximab in the management of patients with TTP.

Thrombotic Thrombocytopenic Purpura: A Thrombotic Disorder Caused by ADAMTS13 Deficiency

“…More recently, rituximab, a chimeric monoclonal anti-CD20, has been used with presumed benefits in patients with protracted TTP. The role of rituximab in the treatment of acute TTP is will be investigated in a planned controlled trial [91]. The experience of calcineurin inhibitors as a treatment of TTP remains limited [92].…”

Thrombotic Thrombocytopenic Purpura: A Moving Target

“…These questions will need to be answered by clinical trials. 34 Idiopathic TTP without ADAMTS13 deficiency. The ability to routinely measure ADAMTS13 level will enable closer study of patients with idiopathic TTP despite having normal ADAMTS13 activity.…”

ADAMTS13 and microvascular thrombosis

“…However, reporting bias may complicate interpretation of the published response rates, and sustained immunological remission appears to be uncommon. While rituximab is apparently valuable for some patients with protracted TTP(75), its role for acute or intermittently recurrent TTP is unclear and will require further investigation (76).…”