Critical Care Medicine

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Critical Care Medicine:
doi: 10.1097/CCM.0b013e31822e9d66
Clinical Investigations

Efficacy and safety of first-line rituximab in severe, acquired thrombotic thrombocytopenic purpura with a suboptimal response to plasma exchange. Experience of the French Thrombotic Microangiopathies Reference Center

Froissart, Antoine MD; Buffet, Marc MD; Veyradier, Agnès MD, PhD; Poullin, Pascale MD; Provôt, François MD; Malot, Sandrine RN; Schwarzinger, Michael PhD; Galicier, Lionel MD; Vanhille, Philippe MD; Vernant, Jean-Paul MD; Bordessoule, Dominique MD; Guidet, Bertrand MD; Azoulay, Elie MD, PhD; Mariotte, Eric MD; Rondeau, Eric MD; Mira, Jean-Paul MD, PhD; Wynckel, Alain MD; Clabault, Karine MD; Choukroun, Gabriel MD, PhD; Presne, Claire MD; Pourrat, Jacques MD; Hamidou, Mohamed MD; Coppo, Paul MD, PhD

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Objective: To assess the efficacy and safety of rituximab in adults responding poorly to standard treatment for severe autoimmune thrombotic thrombocytopenic purpura.

Design: Open-label prospective study. Outcomes in the survivors were compared to those of 53 historical survivors who were given therapeutic plasma exchange alone or with vincristine.

Setting: Hospitals belonging to the Reference Network for Thrombotic Microangiopathies in France.

Patients: Twenty-two adults with either no response or a disease exacerbation when treated with intensive therapeutic plasma exchange.

Intervention: Add-on rituximab therapy, four infusions over 15 days.

Measurements and Main Results: One patient died despite two rituximab infusions. In the rituximab-treated patients, the time to a durable remission was significantly shortened (p = .03), although the plasma volume required to achieve a durable remission was not significantly different compared to the controls. Platelet count recovery occurred within 35 days in all 21 survivors, compared to only 78% of the historical controls (p < .02). Of the rituximab-treated patients, none had a relapse within the first year but three relapsed later on. In patients treated with rituximab, a rapid and profound peripheral B-cell depletion was produced, lasting for 9 months and correlating with higher a disintegrin and metalloproteinase with thrombospondin-13 activity and lower anti-a disintegrin and metalloproteinase with thrombospondin-13 antibody titers. These differences were no longer significant after 12 months. No severe side effects occurred.

Conclusions: Adults with severe thrombocytopenic purpura who responded poorly to therapeutic plasma exchange and who were treated with rituximab had shorter overall treatment duration and reduced 1-yr relapses than historical controls.

© 2012 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins

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