Preemptive rituximab prevents long-term relapses in immune-mediated thrombotic thrombocytopenic purpura

Blood. 2018 Nov 15;132(20):2143-2153. doi: 10.1182/blood-2018-04-840090. Epub 2018 Sep 10.

Abstract

Preemptive rituximab infusions prevent relapses in immune thrombotic thrombocytopenic purpura (iTTP) by maintaining normal ADAMTS13 activity. However, the long-term outcome of these patients and the potential adverse events of this strategy need to be determined. We report the long-term outcome of 92 patients with iTTP in clinical remission who received preemptive rituximab after identification of severe ADAMTS13 deficiency (activity <10%) during the follow-up. Thirty-seven patients had >1 iTTP episode, and the median cumulative relapse incidence before preemptive rituximab was 0.33 episode per year (interquartile range [IQR], 0.23-0.66). After preemptive rituximab, the median cumulative relapse incidence in the whole population decreased to 0 episodes per year (IQR, 0-1.32; P < .001). After preemptive rituximab, ADAMTS13 activity recovery was sustained in 34 patients (37%) during a follow-up of 31.5 months (IQR, 18-65), and severe ADAMTS13 deficiency recurred in 45 patients (49%) after the initial improvement. ADAMTS13 activity usually improved with additional courses of preemptive rituximab. In 13 patients (14%), ADAMTS13 activity remained undetectable after the first rituximab course, but retreatment was efficient in 6 of 10 cases. In total, 14 patients (15%) clinically relapsed, and 19 patients (20.7%) experienced benign adverse effects. Preemptive rituximab treatment was associated with a change in ADAMTS13 conformation in respondent patients. Finally, in the group of 23 historical patients with iTTP and persistently undetectable ADAMTS13 activity, 74% clinically relapsed after a 7-year follow-up (IQR, 5-11). In conclusion, persistently undetectable ADAMTS13 activity in iTTP during remission is associated with a higher relapse rate. Preemptive rituximab reduces clinical relapses by maintaining a detectable ADAMTS13 activity with an advantageous risk-benefit balance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADAMTS13 Protein / chemistry
  • ADAMTS13 Protein / deficiency
  • ADAMTS13 Protein / metabolism
  • Adult
  • Female
  • Humans
  • Immunologic Factors / adverse effects
  • Immunologic Factors / therapeutic use*
  • Male
  • Middle Aged
  • Prospective Studies
  • Protein Conformation / drug effects
  • Purpura, Thrombotic Thrombocytopenic / drug therapy*
  • Purpura, Thrombotic Thrombocytopenic / metabolism
  • Rituximab / adverse effects
  • Rituximab / therapeutic use*
  • Secondary Prevention / methods*
  • Treatment Outcome

Substances

  • Immunologic Factors
  • Rituximab
  • ADAMTS13 Protein
  • ADAMTS13 protein, human