Format

Send to

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

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

Author information

1
Centre de Référence des Microangiopathies Thrombotiques, Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris, Paris, France.
2
Service de Médecine Interne, Centre Hospitalier Universitaire Charles Nicolle, Rouen, France.
3
INSERM U1096, Rouen, France.
4
Laboratory for Thrombosis Research, KU Leuven Campus Kulak Kortrijk, Kortrijk, Belgium.
5
Service de Néphrologie, Hôpital Albert Calmette, Lille, France.
6
Service d'Immuno-Hématologie, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris.
7
Université Paris Diderot Sorbonne Paris Cité, Paris, France.
8
Service de Médecine Interne, Centre Hospitalier Universitaire la Pitié-Salpétrière, Assistance Publique-Hôpitaux de Paris, Paris, France.
9
Service de Néphrologie-Médecine Interne, Hôpital Sud, Amiens, France.
10
Service d'Hémaphérèse, Centre Hospitalier Régional de Marseille Conception, Marseille, France.
11
Service de Néphrologie, Centre Hospitalier Maison Blanche, Reims, France.
12
Unité d'Hémaphérèse, Service d'Hématologie, Centre Hospitalier Universitaire la Pitié-Salpétrière, Assistance Publique-Hôpitaux de Paris, Paris, France.
13
Service de Médecine Interne, Centre Hospitalier Universitaire Fort de France, Fort de France, Martinique.
14
Service de Néphrologie, Centre Hospitalier Universitaire Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris, Paris, France.
15
Service d'Hématologie Clinique et de Thérapie Cellulaire, Centre Hospitalier Universitaire Dupuytren, Limoges, France.
16
Service de Néphrologie, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France.
17
Unité d'Hémaphrèse, Service d'Hématologie, Centre Hospitalier Universitaire de Montpellier, Montpellier, France.
18
Service de Réanimation médicale, Hôpital Gabriel Montpied, Clermont-Ferrand, France.
19
Service de Néphrologie et Immunologie Clinique, Centre Hospitalier Universitaire de Rangueil, Toulouse, France.
20
Service de Néphrologie, Centre Hospitalier Universitaire de Dijon, Dijon, France.
21
Service de Réanimation polyvalente, Centre Hospitalier Universitaire de Nancy, Nancy, France.
22
Service de Néphrologie, Hôpital Bretonneau, Tours, France.
23
Service d'Hématologie, Centre Régional Hospitalier Universitaire de Besançon, Hôpital Jean Minjoz, Besançon, France.
24
Service Médecine interne A, Hôpital Hôtel-Dieu, Nantes, France.
25
Service de Médecine interne, Hôpital Nord, Centre Hospitalier Universitaire de Saint Etienne, Saint Etienne, France.
26
Service d'Hématologie Biologique, Hôpital Lariboisière, Assistance Publique-Hôpitaux de Paris, Paris, France.
27
Service d'Hématologie, Centre Hospitalier Universitaire Saint-Antoine, Assistance Publique-Hôpitaux de Paris, Paris, France; and.
28
Sorbonne Universités, Paris, France.

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.

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center