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Gallo P, De Vincentis A, Terracciani F, Falcomatà A, Pace Palitti V, Russello M, Vignone A, Alvaro D, Tortora R, Biolato M, Pompili M, Calvaruso V, Marzia V, Tizzani M, Caneglias A, Frigo F, Gesualdo M, Marzano A, Rosato V, Claar E, Villani R, Izzi A, Cozzolongo R, Cozzolino A, Airoldi A, Mazzarelli C, Distefano M, Iegri C, Fagiuoli S, Messina V, Ragone E, Sacco R, Cacciatore P, Masutti F, Crocé SL, Moretti A, Flagiello V, Di Pasquale G, Picardi A, Vespasiani-Gentilucci U. Final Results from the First European Real-World Experience on Lusutrombopag Treatment in Cirrhotic Patients with Severe Thrombocytopenia: Insights from the REAl-World Lusutrombopag Treatment in ITalY Study. J Clin Med 2024; 13:3965. [PMID: 38999529 PMCID: PMC11242055 DOI: 10.3390/jcm13133965] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2024] [Revised: 07/01/2024] [Accepted: 07/03/2024] [Indexed: 07/14/2024] Open
Abstract
Background and aims: Management of severe thrombocytopenia poses significant challenges in patients with chronic liver disease. Here, we aimed to evaluate the first real-world European post-marketing cohort of cirrhotic patients treated with lusutrombopag, a thrombopoietin receptor agonist, verifying the efficacy and safety of the drug. Methods: In the REAl-world Lusutrombopag treatment in ITalY (REALITY) study, we collected data from consecutive cirrhotic patients treated with lusutrombopag in 19 Italian hepatology centers, mostly joined to the "Club Epatologi Ospedalieri" (CLEO). Primary and secondary efficacy endpoints were the ability of lusutrombopag to avoid platelet transfusions and to raise the platelet count to ≥50,000/μL, respectively. Treatment-associated adverse events were also collected. Results: A total of 66 patients and 73 cycles of treatment were included in the study, since 5 patients received multiple doses of lusutrombopag over time for different invasive procedures. Fourteen patients (19%) had a history of portal vein thrombosis (PVT). Lusutrombopag determined a significant increase in platelet count [from 37,000 (33,000-44,000/μL) to 58,000 (49,000-82,000), p < 0.001]. The primary endpoint was met in 84% of patients and the secondary endpoint in 74% of patients. Baseline platelet count was the only independent factor associated with response in multivariate logistic regression analysis (OR for any 1000 uL of 1.13, CI95% 1.04-1.26, p 0.01), with a good discrimination power (AUROC: 0.78). Notably, a baseline platelet count ≤ 29,000/μL was identified as the threshold for identifying patients unlikely to respond to the drug (sensitivity of 91%). Finally, de novo PVT was observed in four patients (5%), none of whom had undergone repeated treatment, and no other safety or hemorrhagic events were recorded in the entire population analyzed. Conclusions: In this first European real-world series, lusutrombopag demonstrated efficacy and safety consistent with the results of registrational studies. According to our results, patients with baseline platelet counts ≤29,000/μL are unlikely to respond to the drug.
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Affiliation(s)
- Paolo Gallo
- Fondazione Policlinico Universitario Campus Bio-Medico, 00128 Roma, Italy
| | - Antonio De Vincentis
- Fondazione Policlinico Universitario Campus Bio-Medico, 00128 Roma, Italy
- Research Unit of Internal Medicine, Department of Medicine and Surgery, Università Campus Bio-Medico di Roma, 01128 Roma, Italy
| | | | - Andrea Falcomatà
- Fondazione Policlinico Universitario Campus Bio-Medico, 00128 Roma, Italy
| | | | | | - Anthony Vignone
- Department of Translational and Precision Medicine, Sapienza University of Rome, 00185 Roma, Italy
| | - Domenico Alvaro
- Department of Translational and Precision Medicine, Sapienza University of Rome, 00185 Roma, Italy
| | - Raffaella Tortora
- Liver Unit, Department of Medicine, Cardarelli Hospital, 80131 Napoli, Italy
| | - Marco Biolato
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 01128 Roma, Italy
| | - Maurizio Pompili
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 01128 Roma, Italy
| | - Vincenza Calvaruso
- Gastroenterology and Hepatology Unit, University of Palermo, 90128 Palermo, Italy
| | - Veneziano Marzia
- Gastroenterology and Hepatology Unit, University of Palermo, 90128 Palermo, Italy
| | - Marco Tizzani
- Division of Gastroenterology and Hepatology, A.O.U. Città della Salute e della Scienza di Torino, University of Turin, 10126 Turin, Italy
| | - Alessandro Caneglias
- Division of Gastroenterology and Hepatology, A.O.U. Città della Salute e della Scienza di Torino, University of Turin, 10126 Turin, Italy
| | - Francesco Frigo
- Division of Gastroenterology and Hepatology, A.O.U. Città della Salute e della Scienza di Torino, University of Turin, 10126 Turin, Italy
| | - Marcantonio Gesualdo
- Division of Gastroenterology and Hepatology, A.O.U. Città della Salute e della Scienza di Torino, University of Turin, 10126 Turin, Italy
| | - Alfredo Marzano
- Division of Gastroenterology and Hepatology, A.O.U. Città della Salute e della Scienza di Torino, University of Turin, 10126 Turin, Italy
| | - Valerio Rosato
- UOSD Epatologia, Ospedale Evangelico Betania, 80147 Naples, Italy
| | - Ernesto Claar
- UOSD Epatologia, Ospedale Evangelico Betania, 80147 Naples, Italy
| | - Rosanna Villani
- C.U.R.E. (University Center for Liver Disease Research and Treatment), Liver Unit, Department of Medical and Surgical Sciences, University of Foggia, 71122 Foggia, Italy
| | - Antonio Izzi
- Department of Infectious Diseases, D. Cotugno Hospital, 80131 Napoli, Italy
| | - Raffaele Cozzolongo
- Gastroenterology Unit, National Institute of Gastroenterology, IRCCS “S de Bellis” Research Hospital, 70013 Castellana Grotte, Bari, Italy
| | | | - Aldo Airoldi
- Hepatology and Gastroenterology, ASST GOM Niguarda, 20162 Milan, Italy
| | - Chiara Mazzarelli
- Hepatology and Gastroenterology, ASST GOM Niguarda, 20162 Milan, Italy
| | - Marco Distefano
- UOSD Epatologia-Ospedale Umberto I Siracusa-ASP 8, 96100 Siracusa, Italy
| | - Claudia Iegri
- Gastroenterology, Department of Medicine, University of Milan Bicocca, 20126 Milan, Italy
| | - Stefano Fagiuoli
- Gastroenterology, Department of Medicine, University of Milan Bicocca, 20126 Milan, Italy
| | - Vincenzo Messina
- Infectious Disease Unit, AORN Sant’Anna e San Sebastiano, 81100 Caserta, Italy
| | - Enrico Ragone
- UOC Medicina Infettivologica e dei Trapianti UOS Eco Interventistica, Clinica AORN Dei Colli-Ospedale Monaldi, 80131 Napoli, Italy
| | - Rodolfo Sacco
- Gastroenterology and Digestive Endoscopy Unit, Foggia University Hospital, 71122 Foggia, Italy
| | | | - Flora Masutti
- Liver Clinic, University Hospital of Trieste (Azienda Sanitaria Giuliano-Isontina), 34149 Trieste, Italy
| | - Saveria Lory Crocé
- Liver Clinic, University Hospital of Trieste (Azienda Sanitaria Giuliano-Isontina), 34149 Trieste, Italy
| | | | | | - Giulia Di Pasquale
- Fondazione Policlinico Universitario Campus Bio-Medico, 00128 Roma, Italy
| | - Antonio Picardi
- Fondazione Policlinico Universitario Campus Bio-Medico, 00128 Roma, Italy
- Research Unit of Clinical Medicine and Hepatology, Department of Medicine and Surgery, Università Campus Bio-Medico di Roma, 01128 Roma, Italy
| | - Umberto Vespasiani-Gentilucci
- Fondazione Policlinico Universitario Campus Bio-Medico, 00128 Roma, Italy
- Research Unit of Clinical Medicine and Hepatology, Department of Medicine and Surgery, Università Campus Bio-Medico di Roma, 01128 Roma, Italy
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Gallo P, Terracciani F, Di Pasquale G, Esposito M, Picardi A, Vespasiani-Gentilucci U. Thrombocytopenia in chronic liver disease: Physiopathology and new therapeutic strategies before invasive procedures. World J Gastroenterol 2022; 28:4061-4074. [PMID: 36157107 PMCID: PMC9403422 DOI: 10.3748/wjg.v28.i30.4061] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2022] [Revised: 04/21/2022] [Accepted: 07/18/2022] [Indexed: 02/06/2023] Open
Abstract
Chronic liver disease is characterized by several hematological derangements resulting in a complex and barely rebalanced haemostatic environment. Thrombocytopenia is the most common abnormality observed in these patients and recent advances have led to researchers focus the attention on the multifactorial origin of thrombocytopenia and on the key role of thrombopoietin (TPO) in its physiopathology. Severe thrombocytopenia (platelet count < 50000/μL) complicates the management of patients with chronic liver disease by increasing the potential risk of bleeding for invasive procedures, which may be therefore delayed or canceled even if lifesaving. In the very last years, the development of new drugs which exceed the limits of the current standard of care (platelet transfusions, either immediately before or during the procedure) paves the way to a new scenario in the management of this population of patients. Novel agents, such as the TPO-receptor agonists avatrombopag and lusutrombopag, have been developed in order to increase platelet production as an alternative to platelet transfusions. These agents have demonstrated a good profile in terms of efficacy and safety and will hopefully allow reducing limitations and risks associated with platelet transfusion, without any delay in scheduled interventions. Altogether, it is expected that patients with chronic liver disease will be able to face invasive procedures with one more string in their bow.
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Affiliation(s)
- Paolo Gallo
- Clinical Medicine and Hepatology Unit, Campus Bio-Medico University, Roma 00128, Italy
| | - Francesca Terracciani
- Clinical Medicine and Hepatology Unit, Campus Bio-Medico University, Roma 00128, Italy
| | - Giulia Di Pasquale
- Clinical Medicine and Hepatology Unit, Campus Bio-Medico University, Roma 00128, Italy
| | - Matteo Esposito
- Clinical Medicine and Hepatology Unit, Campus Bio-Medico University, Roma 00128, Italy
| | - Antonio Picardi
- Clinical Medicine and Hepatology Unit, Campus Bio-Medico University, Roma 00128, Italy
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