Rituximab pharmacokinetics during the management of acute idiopathic thrombotic thrombocytopenic purpura

• Published in: Journal of thrombosis and haemostasis Vol. 8; no. 6; pp. 1201 - 1208
• Main Authors: MCDONALD, V., MANNS, K., MACKIE, I. J., MACHIN, S. J., SCULLY, M. A.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.06.2010
• Subjects: Acute Disease; ADAMTS‐13; Adolescent; Adult; Aged; Antibodies, Monoclonal, Murine-Derived - pharmacokinetics; Antibodies, Monoclonal, Murine-Derived - therapeutic use; Female; Humans; Male; Middle Aged; pharmacodynamics; pharmacokinetics; plasma exchange; Purpura, Thrombotic Thrombocytopenic - therapy; Rituximab; TTP; Young Adult
• ISSN: 1538-7933; 1538-7836; 1538-7836
• DOI: 10.1111/j.1538-7836.2010.03818.x

Background: Increasingly, patients with acute, idiopathic, antibody mediated thrombotic thrombocytopenic purpura (TTP) are being treated with rituximab to achieve a durable remission, however, there is the potential that it is removed by plasma exchange (PEX). Objectives: To look at the pharmacokinetics and pharmacodynamics of rituximab in patients with acute idiopathic TTP undergoing PEX. Patients and methods: Patients who received rituximab for acute idiopathic TTP (group 1, n = 30) and a control group (group 2, n = 3) of TTP patients in remission receiving rituximab electively as maintenance were included. Rituximab levels were measured before/after each infusion, before/after PEX and in follow‐up. ADAMTS‐13 activity, anti‐ADAMTS‐13 IgG and CD19% were measured to assess response. Results: The median number of PEX to remission after rituximab was 10 (range 4–25). In group 1 there was no significant incremental rise in the peak serum rituximab level until dose 4. Trough levels were lower in patients who had had PEX since their last rituximab infusion. In the control group, there was an incremental rise in the peak serum rituximab level and all patients had detectable trough levels. The median fall in rituximab per PEX was 65%. All patients achieved CD19 < 1%. In group 1, the median time to undetectable rituximab was 5 months (range 0–12 months) and to B cell return was 7 months (range 3–24 months). ADAMTS‐13 increased and anti‐ADAMTS‐13 fell after therapy. There were three deaths and two relapses in group 1. Relapse was not temporally related to B cell return.