A phase 2 study of the safety and efficacy of rituximab with plasma exchange in acute acquired thrombotic thrombocytopenic purpura

Blood. 2011 Aug 18;118(7):1746-53. doi: 10.1182/blood-2011-03-341131. Epub 2011 Jun 2.

Abstract

The safety and efficacy of weekly rituximab 375 mg/m(2) (×4), given within 3 days of acute TTP admission, with standard therapy (PEX and steroids) was evaluated. Clinical outcomes were compared to historical controls (n = 40) who had not received rituximab. Within the trial group, 15 of 40 required ICU admission and 15% of all cases with the highest troponin T levels on admission were ventilated. Before the second rituximab infusion, 68% of cases had a platelet count > 50 × 10(9)/L and 38% > 150 × 10(9)/L. Fewer PEX were required in whites compared to nonwhite in the rituximab group (mean 14 vs 21, P = .0095). Inpatient stay was reduced by 7 days in the non-ICU trial cases compared to historical controls (P = .04), especially in whites, with a mean reduction of 7 days (P = .05). Ten percent of trial cases relapsed, median, 27 months (17-31 months), compared to 57% in historical controls, median 18 months (3-60 months; P = .0011). There were no excess infections or serious adverse events with rituximab. In conclusion, rituximab appears a safe and effective therapy. Inpatient stay and relapse are significantly reduced in the rituximab cohort. Rituximab should be considered in conjunction with standard therapy on acute presentation of TTP. This study was registered at www.clinicaltrials.gov as NCT009-3713.

Trial registration: ClinicalTrials.gov NCT00937131 NCT00000009 NCT00937131.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • ADAM Proteins / immunology
  • ADAMTS13 Protein
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Murine-Derived / adverse effects
  • Antibodies, Monoclonal, Murine-Derived / immunology
  • Antibodies, Monoclonal, Murine-Derived / therapeutic use*
  • Antigens, CD19 / immunology
  • Female
  • Humans
  • Immunologic Factors / adverse effects
  • Immunologic Factors / immunology
  • Immunologic Factors / therapeutic use*
  • Male
  • Middle Aged
  • Plasma Exchange
  • Purpura, Thrombotic Thrombocytopenic / drug therapy*
  • Purpura, Thrombotic Thrombocytopenic / immunology
  • Purpura, Thrombotic Thrombocytopenic / prevention & control
  • Purpura, Thrombotic Thrombocytopenic / therapy
  • Recurrence
  • Rituximab
  • Young Adult

Substances

  • Antibodies, Monoclonal, Murine-Derived
  • Antigens, CD19
  • Immunologic Factors
  • Rituximab
  • ADAM Proteins
  • ADAMTS13 Protein
  • ADAMTS13 protein, human

Associated data

  • ClinicalTrials.gov/NCT00937131
  • ClinicalTrials.gov/NCT00000009
  • ClinicalTrials.gov/NCT00937131