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

Matthieu Jestin, Ygal Benhamou, An-Sofie Schelpe, Elien Roose, François Provôt, Lionel Galicier, Miguel Hié, Claire Presne, Pascale Poullin, Alain Wynckel, Samir Saheb, Christophe Deligny, Aude Servais, Stéphane Girault, Yahsou Delmas, Tarik Kanouni, Alexandre Lautrette, Dominique Chauveau, Christiane Mousson, Pierre Perez, Jean-Michel Halimi, Anne Charvet-Rumpler, Mohamed Hamidou, Pascal Cathébras, Karen Vanhoorelbeke, Agnès Veyradier and Paul Coppo

Key points

  • TTP patients who display persistent and severe ADAMTS13 deficiency after remission have a relapse rate of 74% during long-term follow-up.

  • Preemptive rituximab can decrease TTP relapses in 85% of patients with a favorable benefit-risk balance.


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/year (IQR, 0.23-0.66). After preemptive rituximab, the median cumulative relapse incidence in the whole population decreased to 0 episode/year [IQR, 0-1.32] (p<0.001). 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 6/10 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 higher relapse rate. Preemptive rituximab reduces clinical relapses by maintaining a detectable ADAMTS13 activity with an advantageous risk-benefit balance.

  • Submitted April 4, 2018.
  • Accepted August 16, 2018.