Sebastiano Bucello1, Pietro Annovazzi2, Paolo Ragonese3, Marta Altieri4, Valeria Barcella5, Roberto Bergamaschi6, Alessia Bianchi3, Giovanna Borriello7, Maria Chiara Buscarinu8, Graziella Callari9, Marco Capobianco10, Fioravante Capone11, Paola Cavalla12, Rosella Cavarretta13, Antonio Cortese4,14, Giovanna De Luca15, Massimiliano Di Filippo16, Vincenzo Dattola17, Roberta Fantozzi18, Elisabetta Ferraro14, Maria Maddalena Filippi19, Claudio Gasperini20, Luigi Maria Edoardo Grimaldi9, Doriana Landi21, Marianna Lo Re10, Giulia Mallucci6, Paolo Manganotti22, Girolama Alessandra Marfia18,21, Massimiliano Mirabella23, Paola Perini24, Marco Pisa25, Sabrina Realmuto26, Margherita Russo27, Valentina Tomassini15,28, Valentina Liliana Adriana Torri-Clerici29, Mauro Zaffaroni2, Cristina Zuliani30, Sofia Zywicki24, Massimo Filippi25,31,32, Luca Prosperini33. 1. Multiple Sclerosis Centre, "E. Muscatello" Hospital - ASP8, Augusta, SR, Italy. 2. UOC Centro Sclerosi Multipla, Neurologia II ASST Valle Olona, PO di Gallarate (VA), Varese, Italy. 3. Department of Biomedicine, Neurosciences and Advanced Diagnostics (BiND), University of Palermo, Palermo, Italy. 4. Multiple Sclerosis Centre, Department of Human Neurosciences, Sapienza University, Rome, Italy. 5. Multiple Sclerosis Centre, Department of Neurology, Papa Giovanni XXIII Hospital, Bergamo, Italy. 6. Multiple Sclerosis Research Centre, IRCCS Mondino Foundation, Pavia, Italy. 7. Multiple Sclerosis Centre, S. Andrea Hospital, Sapienza University, Rome, Italy. 8. Centre for Experimental Neurological Therapies, S. Andrea Hospital, Department of Mental Health and Sensory Organs, Sapienza University, Rome, Italy. 9. Institute Foundation "G. Giglio", Multiple Sclerosis Centre, Cefalù-Palermo, Italy. 10. Centro di Riferimento Regionale Sclerosi Multipla (CReSM), SCDO Neurologia, AOU S. Luigi Gonzaga, Orbassano, TO, Italy. 11. Neurology, Neurophysiology and Neurobiology Unit, Department of Medicine, Università Campus Bio-Medico, Rome, Italy. 12. Multiple Sclerosis Centre, Department of Neurosciences, City of Health and Science University Hospital, Torino, Italy. 13. Multiple Sclerosis Centre, Scientific Institute S. Maria Nascente, Don Carlo Gnocchi Foundation, Milan, Italy. 14. Multiple Sclerosis Centre, S. Filippo Neri Hospital, Rome, Italy. 15. Multiple Sclerosis Centre, Clinical Neurology Unit, SS. Annunziata University Hospital, Chieti, Italy. 16. Multiple Sclerosis Centre, Department of Medicine and Surgery, University Hospital, Perugia, Italy. 17. UOC Neurologia, G.O.M. "Bianchi Melacrino Morelli", Reggio Calabria, Italy. 18. IRCCS Istituto Neurologico Mediterraneo (INM) Neuromed, Pozzilli, IS, Italy. 19. Fatebenefratelli Foundation for Health Research and Education AFaR Division, Rome, Italy. 20. Multiple Sclerosis Centre, Department of Neurosciences, S. Camillo-Forlanini Hospital, C.ne Gianicolense 87, 00152, Rome, Italy. 21. Multiple Sclerosis Clinical and Research Unit, Department of Systems Medicine, Tor Vergata University, Rome, Italy. 22. Clinica Neurologica, Azienda Ospedaliero-Universitaria di Cattinara, Trieste, Italy. 23. Centro Sclerosi Multipla, Fondazione Policlinico Universitario "A. Gemelli" IRCCS Università Cattolica del Sacro Cuore, Rome, Italy. 24. Clinica Neurologica, Centro Sclerosi Multipla, Azienda Ospedaliera di Padova, Padova, Italy. 25. Unit of Neurology, Unit of Neurorehabilitation and Neurophysiology Service, IRCCS San Raffaele Institute, Milan, Italy. 26. Multiple Sclerosis Centre, Neurology Unit and Stroke Unit, AOOR "Villa Sofia-Cervello", Palermo, Italy. 27. Centro Sclerosi Multipla, IRCCS Neurolesi "Bonino-Pulejo", Messina, Italy. 28. Institute for Advanced Biomedical Technologies (ITAB), Department of Neurosciences, Imaging and Clinical Sciences, University G. d'Annunzio of Chieti-Pescara, Chieti, Italy. 29. Centro Sclerosi Multipla, UO Neuroimmunologia e Malattie Neuromuscolari, Fondazione IRCCS Ist. Neurologico C. Besta, Milan, Italy. 30. UOC di Neurologia, Ospedale di Mirano (VE), Mirano, Italy. 31. Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Institute, Milan, Italy. 32. Vita-Salute San Raffaele University, Milan, Italy. 33. Multiple Sclerosis Centre, Department of Neurosciences, S. Camillo-Forlanini Hospital, C.ne Gianicolense 87, 00152, Rome, Italy. luca.prosperini@gmail.com.
Abstract
OBJECTIVE: To identify baseline factors associated with disease activity in patients with relapsing-remitting multiple sclerosis (RRMS) under teriflunomide treatment. METHODS: This was an independent, multi-centre, retrospective post-marketing study. We analysed data of 1,507 patients who started teriflunomide since October 2014 and were regularly followed in 28 Centres in Italy. We reported the proportions of patients who discontinued treatment (after excluding 32 lost to follow-up) and who experienced clinical disease activity, i.e., relapse(s) and/or confirmed disability worsening, as assessed by the Expanded Disability Status Scale (EDSS). Decision tree-based analysis was performed to identify baseline factors associated with clinical disease activity during teriflunomide treatment. RESULTS: At database lock (September 2020), approximately 29% of patients (430 out of 1,475) discontinued teriflunomide because of disease activity (~ 46%), adverse events (~ 37%), poor tolerability (~ 15%), pregnancy planning (~ 2%). Approximately 28% of patients experienced disease activity over a median follow-up of 2.75 years: ~ 9% had relapses but not disability worsening; ~ 13% had isolated disability worsening; ~ 6% had both relapses and disability worsening. The most important baseline factor associated with disease activity (especially disability worsening) was an EDSS > 4.0 (p < 0.001). In patients with moderate disability level (EDSS 2.0-4.0), disease activity occurred more frequently in case of ≥ 1 pre-treatment relapses (p = 0.025). In patients with milder disability level (EDSS < 2.0), disease activity occurred more frequently after previous exposure to ≥ 2 disease-modifying treatments (p = 0.007). CONCLUSIONS: Our study suggests a place-in-therapy for teriflunomide in naïve patients with mild disability level or in those who switched their initial treatment for poor tolerability. Adverse events related with teriflunomide were consistent with literature data, without any new safety concern.
OBJECTIVE: To identify baseline factors associated with disease activity in patients with relapsing-remitting multiple sclerosis (RRMS) under teriflunomide treatment. METHODS: This was an independent, multi-centre, retrospective post-marketing study. We analysed data of 1,507 patients who started teriflunomide since October 2014 and were regularly followed in 28 Centres in Italy. We reported the proportions of patients who discontinued treatment (after excluding 32 lost to follow-up) and who experienced clinical disease activity, i.e., relapse(s) and/or confirmed disability worsening, as assessed by the Expanded Disability Status Scale (EDSS). Decision tree-based analysis was performed to identify baseline factors associated with clinical disease activity during teriflunomide treatment. RESULTS: At database lock (September 2020), approximately 29% of patients (430 out of 1,475) discontinued teriflunomide because of disease activity (~ 46%), adverse events (~ 37%), poor tolerability (~ 15%), pregnancy planning (~ 2%). Approximately 28% of patients experienced disease activity over a median follow-up of 2.75 years: ~ 9% had relapses but not disability worsening; ~ 13% had isolated disability worsening; ~ 6% had both relapses and disability worsening. The most important baseline factor associated with disease activity (especially disability worsening) was an EDSS > 4.0 (p < 0.001). In patients with moderate disability level (EDSS 2.0-4.0), disease activity occurred more frequently in case of ≥ 1 pre-treatment relapses (p = 0.025). In patients with milder disability level (EDSS < 2.0), disease activity occurred more frequently after previous exposure to ≥ 2 disease-modifying treatments (p = 0.007). CONCLUSIONS: Our study suggests a place-in-therapy for teriflunomide in naïve patients with mild disability level or in those who switched their initial treatment for poor tolerability. Adverse events related with teriflunomide were consistent with literature data, without any new safety concern.
Authors: H M Cherwinski; R G Cohn; P Cheung; D J Webster; Y Z Xu; J P Caulfield; J M Young; G Nakano; J T Ransom Journal: J Pharmacol Exp Ther Date: 1995-11 Impact factor: 4.030
Authors: Michael Guger; Michael Matthias Ackerl; Martin Heine; Christiane Hofinger-Renner; Heinrich Karl Spiss; Andrea Taut; Karin Unger; Fritz Leutmezer Journal: eNeurologicalSci Date: 2022-03-07