1. A regimen with caplacizumab, immunosuppression, and plasma exchange prevents unfavorable outcomes in immune-mediated TTP
- Author
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Jean-François Augusto, Naïke Bigé, Lionel Galicier, Alain Wynckel, Nihal Martis, Michael Bubenheim, Ygal Benhamou, Antoine Dossier, Claire Presne, Elie Azoulay, Virginie Rieu, Agnès Veyradier, Sandrine Malot, François Provôt, Christelle Barbet, Miguel Hie, Amélie Seguin, Sten de Witte, Pascale Poullin, M. Ulrich, Paul Coppo, Thierry Krummel, François Lhote, Yahsou Delmas, Pierre Perez, Anne Charvet Rumpler, Ruben Benainous, Olivier Moranne, Salvy-Córdoba, Nathalie, Centre de référence des microangiopathies thrombotiques [CHU Saint-Antoine] (Cnr-mat), Service d'hématologie clinique et de thérapie cellulaire [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Laboratoire d'Hématologie et d'Immunologie [CHU Saint-Antoine], Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Centre d'Investigation Clinique [CHU Rouen] (CIC Rouen), Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Cité - UFR Médecine [Santé] (UPCité UFR Médecine), Université Paris Cité (UPCité), Service d'Immunopathologie [Hôpital Saint-Louis, Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Service d'Anesthésie réanimation [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital de la Timone [CHU - APHM] (TIMONE), Service de Néphrologie [Hôpital Albert Calmette], Hôpital Albert Calmette [Lille], Centre Hospitalier Universitaire de Nice (CHU Nice), CHU Amiens-Picardie, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Service de médecine interne [Avicenne], Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Centre hospitalier universitaire de Nantes (CHU Nantes), Service de Médecine Interne 2, maladies auto-immunes et systémiques [CHU Pitié-Salpêtrière], Institut E3M [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Hôpital Maison Blanche, Centre Hospitalier Universitaire de Reims (CHU Reims), CHU Bordeaux [Bordeaux], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Hôpital Brabois, CHU, Partenaires INRAE, Service de Médecine Interne [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Hôpital Delafontaine, Centre Hospitalier de Saint-Denis [Ile-de-France], Centre hospitalier [Valenciennes, Nord], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre Hospitalier Libourne, Service de néphrologie et hémodialyse [CHU de Strasbourg], CHU Strasbourg, Service d’Hématologie Biologique [CHU Lariboisière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Institut de Recherche Saint-Louis - Hématologie Immunologie Oncologie (Département de recherche de l’UFR de médecine, ex- Institut Universitaire Hématologie-IUH) (IRSL), Normandie Université (NU)-Normandie Université (NU), Endothélium, valvulopathies et insuffisance cardiaque (EnVI), Université de Rouen Normandie (UNIROUEN), and Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)
- Subjects
Compassionate Use Trials ,Male ,[SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology ,MESH: Combined Modality Therapy ,MESH: Von Willebrand Factor ,medicine.medical_treatment ,Plenary Paper ,Salvage therapy ,030204 cardiovascular system & hematology ,Severity of Illness Index ,Biochemistry ,MESH: Historically Controlled Study ,0302 clinical medicine ,Adrenal Cortex Hormones ,Prospective Studies ,Thiamine ,Prospective cohort study ,MESH: Treatment Outcome ,MESH: Middle Aged ,Plasma Exchange ,MESH: Compassionate Use Trials ,[SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology ,Immunosuppression ,Hematology ,Middle Aged ,MESH: Plasma Exchange ,[SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences ,Combined Modality Therapy ,[SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences ,Treatment Outcome ,MESH: Thromboembolism ,030220 oncology & carcinogenesis ,Disease Progression ,Drug Therapy, Combination ,Female ,MESH: Disease Progression ,Rituximab ,MESH: Rituximab ,MESH: Hemorrhage ,medicine.drug ,Adult ,medicine.medical_specialty ,MESH: Purpura, Thrombotic Thrombocytopenic ,Immunology ,Thrombotic thrombocytopenic purpura ,ADAMTS13 Protein ,Hemorrhage ,MESH: Single-Domain Antibodies ,MESH: Adrenal Cortex Hormones ,03 medical and health sciences ,Thromboembolism ,MESH: Severity of Illness Index ,Internal medicine ,von Willebrand Factor ,medicine ,Humans ,MESH: Platelet Count ,MESH: ADAMTS13 Protein ,Adverse effect ,Immunosuppression Therapy ,MESH: Humans ,Purpura, Thrombotic Thrombocytopenic ,Platelet Count ,business.industry ,Historically Controlled Study ,MESH: Adult ,Cell Biology ,Single-Domain Antibodies ,medicine.disease ,MESH: Male ,MESH: Prospective Studies ,MESH: Drug Therapy, Combination ,Regimen ,Caplacizumab ,business ,MESH: Female - Abstract
The anti–von Willebrand factor nanobody caplacizumab was licensed for adults with immune-mediated thrombotic thrombocytopenic purpura (iTTP) based on prospective controlled trials. However, few data are available on postmarketing surveillance. We treated 90 iTTP patients with a compassionate frontline triplet regimen associating therapeutic plasma exchange (TPE), immunosuppression with corticosteroids and rituximab, and caplacizumab. Outcomes were compared with 180 historical patients treated with the standard frontline treatment (TPE and corticosteroids, with rituximab as salvage therapy). The primary outcome was a composite of refractoriness and death within 30 days since diagnosis. Key secondary outcomes were exacerbations, time to platelet count recovery, the number of TPE, and the volume of plasma required to achieve durable remission. The percentage of patients in the triplet regimen with the composite primary outcome was 2.2% vs 12.2% in historical patients (P = .01). One elderly patient in the triplet regimen died of pulmonary embolism. Patients from this cohort experienced less exacerbations (3.4% vs 44%, P < .01); they recovered durable platelet count 1.8 times faster than historical patients (95% confidence interval, 1.41-2.36; P < .01), with fewer TPE sessions and lower plasma volumes (P < .01 both). The number of days in hospital was 41% lower in the triplet regimen than in the historical cohort (13 vs 22 days; P < .01). Caplacizumab-related adverse events occurred in 46 patients (51%), including 13 major or clinically relevant nonmajor hemorrhagic events. Associating caplacizumab to TPE and immunosuppression, by addressing the 3 processes of iTTP pathophysiology, prevents unfavorable outcomes and alleviates the burden of care.
- Published
- 2021
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