Prolonged response after TPO-RA discontinuation in primary ITP: results of a prospective multicenter study - Université de Picardie Jules Verne Accéder directement au contenu
Article Dans Une Revue Blood Année : 2023

Prolonged response after TPO-RA discontinuation in primary ITP: results of a prospective multicenter study

1 Service de médecine interne [Mondor]
2 CNR - INSERM U1151 - National Cystic Fibrosis Reference Center [CHU Necker]
3 Equipe Inserm U1163 - Immunogenetics of pediatric autoimmune diseases
4 CHU Henri Mondor [Créteil]
5 IMRB - Institut Mondor de Recherche Biomédicale
6 INEM - UM 111 (UMR 8253 / U1151) - Institut Necker Enfants-Malades
7 U955 Inserm - UPEC - IMRB - CEPIA/"Clinical Epidemiology And Ageing : Geriatrics, Primary Care and Public Health" [Créteil]
8 Hôpital Haut-Lévêque [CHU Bordeaux]
9 UB - Université de Bordeaux
10 CHU Saint-Antoine [AP-HP]
11 AP-HP - Hopital Saint-Louis [AP-HP]
12 CHU Caen
13 Hôpital Necker - Enfants Malades [AP-HP]
14 Service de médecine interne et immunologie clinique (SOC 1) [CHU de Dijon]
15 IMVA - U1184 - Immunologie des Maladies Virales et Autoimmunes
16 Hôpital Bicêtre [AP-HP, Le Kremlin-Bicêtre]
17 Service de Médecine Interne - Immunologie Clinique [AP-HP Bicêtre]
18 IDMIT - Infectious Diseases Models for Innovative Therapies
19 CIC 1436 - Centre d'investigation clinique de Toulouse
20 CHU Nantes - Centre Hospitalier Universitaire de Nantes = Nantes University Hospital
21 U1064 Inserm - CR2TI - Centre de Recherche en Transplantation et Immunologie - Center for Research in Transplantation and Translational Immunology
22 ITUN - Institut de transplantation urologie-néphrologie
23 HCL - Hospices Civils de Lyon
24 CHU Amiens-Picardie
25 HEMATIM - HEMATIM - Hématopoïèse et immunologie - UR UPJV 4666
26 INFINITE - Institute for Translational Research in Inflammation - U 1286
Etienne Riviere
  • Fonction : Auteur
Stéphane Cheze
  • Fonction : Auteur
Olivier Fain
Nihal Martis
Anne-Sophie Morin
  • Fonction : Auteur
Antoinette Perlat
  • Fonction : Auteur
Thomas Le Gallou
  • Fonction : Auteur
Frédérique Roy-Peaud
  • Fonction : Auteur
Ailsa Robbins
  • Fonction : Auteur
Jean-Christophe Lega
Mathieu Puyade
  • Fonction : Auteur
Thibault Comont
  • Fonction : Auteur
Nicolas Limal
  • Fonction : Auteur
Laetitia Languille
  • Fonction : Auteur
Anissa Zarour
  • Fonction : Auteur
Marine Luka
  • Fonction : Auteur
Mickaël Mathieu Ménager
Thibaut Belmondo
  • Fonction : Auteur
Sophie Hue
Florence Canoui-Poitrine
Marc Michel
  • Fonction : Auteur
Bertrand Godeau
  • Fonction : Auteur
Matthieu Mahevas
  • Fonction : Auteur

Résumé

Sustained response off-treatment (SROT) after thrombopoietin receptor agonist (TPO-RA) discontinuation has been reported in ITP. This prospective multicenter interventional study enrolled adults with persistent or chronic primary ITP and complete response on TPO-RAs. The primary endpoint was the proportion of patients achieving SROT (platelet count > 30x109/L and no bleeding) at W24 with no other ITP-specific medications. Secondary endpoints included the proportion of sustained complete response off-treatment (SCROT, platelet count > 100x109/L and no bleeding) and SROT at W52, bleeding events, and pattern of response to a new course of TPO-RAs. We included 48 patients with median (IQR) age 58.5 years (41-73.5); 30/48 (63%) had chronic ITP at TPO-RA initiation. In the intention-to-treat analysis, 27/48 (56.2%, 95% CI, 41.2-70.5) achieved SROT; 15/48 (31.3%; 95% CI, 18.9-44.5) achieved SCROT at W24, and 25/48 (52.1%; 95% CI, 37.2-66.7) achieved respectively SROT and 14/48 (29.2%; 95% CI, 17.2-42.3) SCROT at W52. No severe bleeding episode occurred in patients who relapsed. Among patients re-challenged with TPO-RA, 11/12 achieved CR. We found no significant clinical predictors of SROT at W24. Single-cell RNA-seq revealed enrichment of a "TNFα signaling via NF-κB" signature in CD8+ T cells of patients with no sustained response after TPO-RA discontinuation, which was further confirmed by a significant overexpression of CD69 on CD8+ T cells at baseline in these patients as compared with those achieving SCROT/SROT. Our results strongly support a strategy based of progressive tapering and discontinuation of TPO-RAs for patients with chronic ITP who achieved a stable CR on treatment. Clinical trial number: NCT03119974

Dates et versions

hal-04032447 , version 1 (16-03-2023)

Identifiants

Citer

Stephanie Guillet, Etienne Crickx, Imane Azzaoui, Pascal Chappert, Emmanuelle Boutin, et al.. Prolonged response after TPO-RA discontinuation in primary ITP: results of a prospective multicenter study. Blood, 2023, ⟨10.1182/blood.2022018665⟩. ⟨hal-04032447⟩
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