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

Antoine Froissart, Marc Buffet, Agnès Veyradier, Pascale Poullin, François Provôt, Sandrine Malot, Michael Schwarzinger, Lionel Galicier, Philippe Vanhille, Jean-Paul Vernant, Dominique Bordessoule, Bertrand Guidet, Elie Azoulay, Eric Mariotte, Eric Rondeau, Jean-Paul Mira, Alain Wynckel, Karine Clabault, Gabriel Choukroun, Claire Presne, Jacques Pourrat, Mohamed Hamidou, Paul Coppo
Critical Care Medicine 2012, 40 (1): 104-11

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.

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