Journal of Clinical Medicine (Jul 2024)
Influence of Safety Warnings on the Prescribing Attitude of JAK Inhibitors for Rheumatoid Arthritis in Italy
- Marino Paroli,
- Andrea Becciolini,
- Alberto Lo Gullo,
- Simone Parisi,
- Elena Bravi,
- Romina Andracco,
- Valeria Nucera,
- Francesca Ometto,
- Federica Lumetti,
- Antonella Farina,
- Patrizia Del Medico,
- Matteo Colina,
- Viviana Ravagnani,
- Palma Scolieri,
- Maddalena Larosa,
- Marta Priora,
- Elisa Visalli,
- Olga Addimanda,
- Rosetta Vitetta,
- Alessandro Volpe,
- Alessandra Bezzi,
- Francesco Girelli,
- Aldo Biagio Molica Colella,
- Rosalba Caccavale,
- Eleonora Di Donato,
- Giuditta Adorni,
- Daniele Santilli,
- Gianluca Lucchini,
- Eugenio Arrigoni,
- Ilaria Platè,
- Natalia Mansueto,
- Aurora Ianniello,
- Enrico Fusaro,
- Maria Chiara Ditto,
- Vincenzo Bruzzese,
- Dario Camellino,
- Gerolamo Bianchi,
- Francesca Serale,
- Rosario Foti,
- Giorgio Amato,
- Francesco De Lucia,
- Ylenia Dal Bosco,
- Roberta Foti,
- Massimo Reta,
- Alessia Fiorenza,
- Guido Rovera,
- Antonio Marchetta,
- Maria Cristina Focherini,
- Fabio Mascella,
- Simone Bernardi,
- Gilda Sandri,
- Dilia Giuggioli,
- Carlo Salvarani,
- Maria Ilenia De Andres,
- Veronica Franchina,
- Francesco Molica Colella,
- Giulio Ferrero,
- Bernd Raffeiner,
- Alarico Ariani
Affiliations
- Marino Paroli
- Department of Clinical, Internist, Anesthesiologic and Cardiovascular Sciences, Sapienza University of Rome, 00185 Rome, Italy
- Andrea Becciolini
- Internal Medicine and Rheumatology Unit, University Hospital of Parma, 43126 Parma, Italy
- Alberto Lo Gullo
- Rheumatology Unit, ARNAS Garibaldi, 95124 Catania, Italy
- Simone Parisi
- Rheumatology Department, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, 10126 Turin, Italy
- Elena Bravi
- Rheumatology Unit, Guglielmo da Saliceto Hospital, 29121 Piacenza, Italy
- Romina Andracco
- Rheumatology Unit, ASL1 Liguria, 18038 Bussana di Sanremo, Italy
- Valeria Nucera
- Rheumatology Unit, ASL Novara, 28100 Novara, Italy
- Francesca Ometto
- Rheumatology Unit, Azienda ULSS 6 Euganea, 35131 Padua, Italy
- Federica Lumetti
- Rheumatology Unit, Azienda USL of Modena and AOU Policlinico of Modena, 41100 Modena, Italy
- Antonella Farina
- Internal Medicine Unit, Augusto Murri Hospital, 63900 Fermo, Italy
- Patrizia Del Medico
- Internal Medicine Unit, Civitanova Marche Hospital, 62012 Civitanova Marche, Italy
- Matteo Colina
- Rheumatology Unit, Internal Medicine Division, Department of Medicine and Oncology, Santa Maria della Scaletta Hospital, 40026 Imola, Italy
- Viviana Ravagnani
- Rheumatology Unit, Santa Chiara Hospital APSS—Trento, 38122 Trento, Italy
- Palma Scolieri
- Rheumatology Unit, Nuovo Regina Margherita Hospital, 00154 Rome, Italy
- Maddalena Larosa
- Division of Rheumatology, Department of Medical Specialties, Azienda Sanitaria Locale 3 Genovese, 16132 Genoa, Italy
- Marta Priora
- Rheumatology Unit, ASL CN1, 12100 Cuneo, Italy
- Elisa Visalli
- Rheumatology Unit, Policlinico San Marco Hospital, 95121 Catania, Italy
- Olga Addimanda
- Rheumatology Unit, AUSL of Bologna—Policlinico Sant’Orsola—AOU—IRCCS of Bologna, 40138 Bologna, Italy
- Rosetta Vitetta
- Rheumatology Unit, ASL VC Sant’Andrea Hospital, 13100 Vercelli, Italy
- Alessandro Volpe
- Rheumatology Unit, IRCCS Sacro Cuore Don Calabria Hospital, 37024 Negrar di Valpolicella, Italy
- Alessandra Bezzi
- Internal Medicine and Rheumatology Unit, AUSL della Romagna—Rimini, 47924 Rimini, Italy
- Francesco Girelli
- Rheumatology Unit, G.B. Morgagni—L. Pierantoni Hospital, 47121 Forlì, Italy
- Aldo Biagio Molica Colella
- Departmental Unit of Rheumatology, Azienda Ospedaliera Papardo, 98158 Messina, Italy
- Rosalba Caccavale
- Department of Clinical, Internist, Anesthesiologic and Cardiovascular Sciences, Sapienza University of Rome, 00185 Rome, Italy
- Eleonora Di Donato
- Internal Medicine and Rheumatology Unit, University Hospital of Parma, 43126 Parma, Italy
- Giuditta Adorni
- Internal Medicine and Rheumatology Unit, University Hospital of Parma, 43126 Parma, Italy
- Daniele Santilli
- Internal Medicine and Rheumatology Unit, University Hospital of Parma, 43126 Parma, Italy
- Gianluca Lucchini
- Internal Medicine and Rheumatology Unit, University Hospital of Parma, 43126 Parma, Italy
- Eugenio Arrigoni
- Rheumatology Unit, Guglielmo da Saliceto Hospital, 29121 Piacenza, Italy
- Ilaria Platè
- Rheumatology Unit, Guglielmo da Saliceto Hospital, 29121 Piacenza, Italy
- Natalia Mansueto
- Rheumatology Unit, ASL1 Liguria, 18038 Bussana di Sanremo, Italy
- Aurora Ianniello
- Rheumatology Unit, ASL Novara, 28100 Novara, Italy
- Enrico Fusaro
- Rheumatology Department, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, 10126 Turin, Italy
- Maria Chiara Ditto
- Rheumatology Department, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, 10126 Turin, Italy
- Vincenzo Bruzzese
- Rheumatology Unit, Nuovo Regina Margherita Hospital, 00154 Rome, Italy
- Dario Camellino
- Division of Rheumatology, Department of Medical Specialties, Azienda Sanitaria Locale 3 Genovese, 16132 Genoa, Italy
- Gerolamo Bianchi
- Division of Rheumatology, Department of Medical Specialties, Azienda Sanitaria Locale 3 Genovese, 16132 Genoa, Italy
- Francesca Serale
- Rheumatology Unit, ASL CN1, 12100 Cuneo, Italy
- Rosario Foti
- Rheumatology Unit, Policlinico San Marco Hospital, 95121 Catania, Italy
- Giorgio Amato
- Rheumatology Unit, Policlinico San Marco Hospital, 95121 Catania, Italy
- Francesco De Lucia
- Rheumatology Unit, Policlinico San Marco Hospital, 95121 Catania, Italy
- Ylenia Dal Bosco
- Rheumatology Unit, Policlinico San Marco Hospital, 95121 Catania, Italy
- Roberta Foti
- Rheumatology Unit, Policlinico San Marco Hospital, 95121 Catania, Italy
- Massimo Reta
- Rheumatology Unit, AUSL of Bologna—Policlinico Sant’Orsola—AOU—IRCCS of Bologna, 40138 Bologna, Italy
- Alessia Fiorenza
- Rheumatology Unit, ASL VC Sant’Andrea Hospital, 13100 Vercelli, Italy
- Guido Rovera
- Rheumatology Unit, ASL VC Sant’Andrea Hospital, 13100 Vercelli, Italy
- Antonio Marchetta
- Rheumatology Unit, IRCCS Sacro Cuore Don Calabria Hospital, 37024 Negrar di Valpolicella, Italy
- Maria Cristina Focherini
- Internal Medicine and Rheumatology Unit, AUSL della Romagna—Rimini, 47924 Rimini, Italy
- Fabio Mascella
- Internal Medicine and Rheumatology Unit, AUSL della Romagna—Rimini, 47924 Rimini, Italy
- Simone Bernardi
- Rheumatology Unit, G.B. Morgagni—L. Pierantoni Hospital, 47121 Forlì, Italy
- Gilda Sandri
- Rheumatology Unit, University of Modena and Reggio Emilia, 41125 Modena, Italy
- Dilia Giuggioli
- Rheumatology Unit, University of Modena and Reggio Emilia, 41125 Modena, Italy
- Carlo Salvarani
- Rheumatology Unit, University of Modena and Reggio Emilia, 41125 Modena, Italy
- Maria Ilenia De Andres
- Rheumatology Unit, ARNAS Garibaldi, 95124 Catania, Italy
- Veronica Franchina
- Medical Oncology Unit, Azienda Ospedaliera Papardo, 98158 Messina, Italy
- Francesco Molica Colella
- Medicine Unit, Milano-Bicocca University, 20126 Milan, Italy
- Giulio Ferrero
- Unit of Diagnostic and Interventional Radiology, Santa Corona Hospital, 17027 Pietra Ligure, Italy
- Bernd Raffeiner
- Department of Rheumatology, Bolzano Central Hospital, 39100 Bolzano, Italy
- Alarico Ariani
- Internal Medicine and Rheumatology Unit, University Hospital of Parma, 43126 Parma, Italy
- DOI
- https://doi.org/10.3390/jcm13133929
- Journal volume & issue
-
Vol. 13,
no. 13
p. 3929
Abstract
Background/Objectives: The Janus kinase inhibitors (JAKi) tofacitinib (TOFA), baricitinib (BARI), upadacitinib (UPA), and filgotinib (FILGO) are effective drugs for the treatment of rheumatoid arthritis. However, the US Food and Drug Administration (FDA) raised concerns about the safety of TOFA after its approval. This prompted the European Medicines Agency (EMA) to issue two safety warnings for limiting TOFA use, then extended a third warning to all JAKi in patients at high risk of developing serious adverse effects (SAE). These include thrombosis, major adverse cardiac events (MACE), and cancer. The purpose of this work was to analyze how the first two safety warnings from the EMA affected the prescribing of JAKi by rheumatologists in Italy. Methods: All patients with rheumatoid arthritis who had been prescribed JAKi for the first time in a 36-month period from 1 July 2019, to 30 June 2022 were considered. Data were obtained from the medical records of 29 Italian tertiary referral rheumatology centers. Patients were divided into three groups of 4 months each, depending on whether the JAKi prescription had occurred before the EMA’s first safety alert (1 July–31 October 2019, Group 1), between the first and second alerts (1 November 2019–29 February 2020, Group 2), or between the second and third alerts (1 March 2021–30 June 2021, Group 3). The percentages and absolute changes in the patients prescribed the individual JAKi were analyzed. Differences among the three groups of patients regarding demographic and clinical characteristics were also assessed. Results: A total of 864 patients were prescribed a JAKi during the entire period considered. Of these, 343 were identified in Group 1, 233 in Group 2, and 288 in Group 3. An absolute reduction of 32% was observed in the number of patients prescribed a JAKi between Group 1 and Group 2 and 16% between Group 1 and Group 3. In contrast, there was a 19% increase in the prescription of a JAKi in patients between Group 2 and Group 3. In the first group, BARI was the most prescribed drug (227 prescriptions, 66.2% of the total), followed by TOFA (115, 33.5%) and UPA (1, 0.3%). In the second group, the most prescribed JAKi was BARI (147, 63.1%), followed by TOFA (65, 27.9%) and UPA (33, 11.5%). In the third group, BARI was still the most prescribed JAKi (104 prescriptions, 36.1%), followed by UPA (89, 30.9%), FILGO (89, 21.5%), and TOFA (33, 11.5%). The number of patients prescribed TOFA decreased significantly between Group 1 and Group 2 and between Group 2 and Group 3 (p ˂ 0.01). The number of patients who were prescribed BARI decreased significantly between Group 1 and Group 2 and between Group 2 and Group 3 (p ˂ 0.01). In contrast, the number of patients prescribed UPA increased between Group 2 and Group 3 (p ˂ 0.01). Conclusions: These data suggest that the warnings issued for TOFA were followed by a reduction in total JAKi prescriptions. However, the more selective JAKi (UPA and FILGO) were perceived by prescribers as favorable in terms of the risk/benefit ratio, and their use gradually increased at the expense of the other molecules.
Keywords