Francesco Saccà1, Roberta Lanzillo1, Alessio Signori2, Giorgia T Maniscalco3, Elisabetta Signoriello4, Salvatore Lo Fermo5, Annamaria Repice6, Pietro Annovazzi7, Damiano Baroncini7, Marinella Clerico8, Eleonora Binello9, Raffaella Cerqua10, Giorgia Mataluni11, Simona Bonavita12, Luigi Lavorgna12, Ignazio Roberto Zarbo13, Alice Laroni14, Silvia Rossi15, Lorena Pareja Gutierrez15, Sara La Gioia16, Barbara Frigeni16, Valeria Barcella16, Jessica Frau17, Eleonora Cocco17, Giuseppe Fenu17, Valentina Torri Clerici15, Arianna Sartori18, Sarah Rasia19, Cinzia Cordioli19, Alessia Di Sapio20, Simona Pontecorvo21, Roberta Grasso22, Caterina Barrilà23, Cinzia Valeria Russo1, Sabrina Esposito12, Domenico Ippolito12, Francesca Bovis2, Fabio Gallo2, Maria Pia Sormani2. 1. Multiple Sclerosis Center, Department of Neuroscience, Reproductive Sciences and Odontostomatology, Federico II University, Naples, Italy. 2. Department of Health Sciences (DISSAL), Section of Biostatistics, University of Genova, Genova, Italy. 3. Neurological Clinic and Multiple Sclerosis Center, "AORN A.Cardarelli," Naples, Italy. 4. Multiple Sclerosis Center, II Division of Neurology, University of Campania Luigi Vanvitelli, Naples, Italy. 5. Neurological Clinic, A.O.U. Policlinico Vittorio Emanuele, Catania, Italy. 6. 2nd Neurology Unit and CRRSM (Regional Referral Multiple Sclerosis Center), Careggi University Hospital and University of Florence, Florence, Italy. 7. Multiple Sclerosis Study Center, ASST Valle Olona, PO di Gallarate (VA), Gallarate, Italy. 8. Clinical and Biological Sciences Department, Neurology Unit, University of Torino, San Luigi Gonzaga University Hospital, Torino, Italy. 9. Centro Sclerosi Multipla, Dipartimento di Neuroscienze, AOU Città della Salute e della Scienza di Torino, Torino, Italy. 10. Neurological Clinic, Department of Experimental and Clinical Medicine, Marche Polytechnic University, Ancona, Italy. 11. Policlinico Tor Vergata, Rome, Italy. 12. Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences, University of Campania Luigi Vanvitelli, Naples, Italy. 13. Department of Clinical and Experimental Medicine, University of Sassari, Sassari, Italy. 14. Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health and Center of Excellence for Biomedical Research (CEBR) and IRCCS San Martino-IST, University of Genova, Genova, Italy. 15. Neuro-immunology and Neuromuscolar Diseases Unit, IRCCS Foundation Carlo Besta Neurological Institute, Milan, Italy. 16. Centro Sclerosi Multipla, ASST Papa Giovanni XXIII di Bergamo, Bergamo, Italy. 17. Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy. 18. Neurology Clinic, Department of Medical, Surgical, and Health Sciences, University of Trieste, Trieste, Italy. 19. Multiple Sclerosis Center, ASST Spedali Civili, PO di Montichiari (BS), Montichiari, Italy. 20. 2nd Neurology Unit and CRRSM (Regional Referral Multiple Sclerosis Center), AOU San Luigi Gonzaga, Torino, Italy; Regina Montis Regalis Hospital, Mondovì, Italy. 21. Department of Neurology and Psychiatry, Sapienza University of Rome, Rome, Italy. 22. Neurologia Universitaria OORR, Foggia, Italy. 23. Department of Neurology, Valduce Hospital, Como, Italy.
Abstract
BACKGROUND: With many options now available, first therapy choice is challenging in multiple sclerosis (MS) and depends mainly on neurologist and patient preferences. OBJECTIVES: To identify prognostic factors for early switch after first therapy choice. METHODS: Newly diagnosed relapsing-remitting MS patients from 24 Italian centers were included. We evaluated the association of baseline demographics, clinical, and magnetic resonance imaging (MRI) data to the switch probability for lack of efficacy or intolerance/safety with a multivariate Cox analysis and estimated switch rates by competing risks models. RESULTS: We enrolled 3025 patients. The overall switch frequency was 48% after 3 years. Switch risk for lack of efficacy was lower with fingolimod (hazard ratio (HR) = 0.50; p = 0.009), natalizumab (HR = 0.13; p < 0.001), dimethyl-fumarate (HR = 0.60; p = 0.037), teriflunomide (HR = 0.21; p = 0.031) as compared to interferons. Younger age (HR = 0.96; p < 0.001), diagnosis delay (HR = 1.23; p = 0.021), higher baseline Expanded Disability Status Scale (HR = 1.17; p = 0.001), and spinal cord lesions (HR = 1.46; p = 0.001) were independently associated with higher inefficacy switch rates. We found lower switch for intolerance/safety with glatiramer acetate (HR = 0.61; p = 0.001), fingolimod (HR = 0.35; p = 0.002), and dimethyl-fumarate (HR = 0.57; p = 0.022) as compared to interferons, while it increased with natalizumab (HR = 1.43; p = 0.022). Comorbidities were associated with intolerance switch (HR = 1.28; p = 0.047). CONCLUSION: Several factors are associated with higher switch risk in patients starting a first-line therapy and could be integrated in the decision-making process of first treatment choice.
BACKGROUND: With many options now available, first therapy choice is challenging in multiple sclerosis (MS) and depends mainly on neurologist and patient preferences. OBJECTIVES: To identify prognostic factors for early switch after first therapy choice. METHODS: Newly diagnosed relapsing-remitting MSpatients from 24 Italian centers were included. We evaluated the association of baseline demographics, clinical, and magnetic resonance imaging (MRI) data to the switch probability for lack of efficacy or intolerance/safety with a multivariate Cox analysis and estimated switch rates by competing risks models. RESULTS: We enrolled 3025 patients. The overall switch frequency was 48% after 3 years. Switch risk for lack of efficacy was lower with fingolimod (hazard ratio (HR) = 0.50; p = 0.009), natalizumab (HR = 0.13; p < 0.001), dimethyl-fumarate (HR = 0.60; p = 0.037), teriflunomide (HR = 0.21; p = 0.031) as compared to interferons. Younger age (HR = 0.96; p < 0.001), diagnosis delay (HR = 1.23; p = 0.021), higher baseline Expanded Disability Status Scale (HR = 1.17; p = 0.001), and spinal cord lesions (HR = 1.46; p = 0.001) were independently associated with higher inefficacy switch rates. We found lower switch for intolerance/safety with glatiramer acetate (HR = 0.61; p = 0.001), fingolimod (HR = 0.35; p = 0.002), and dimethyl-fumarate (HR = 0.57; p = 0.022) as compared to interferons, while it increased with natalizumab (HR = 1.43; p = 0.022). Comorbidities were associated with intolerance switch (HR = 1.28; p = 0.047). CONCLUSION: Several factors are associated with higher switch risk in patients starting a first-line therapy and could be integrated in the decision-making process of first treatment choice.
Authors: Heinz Wiendl; Ralf Gold; Thomas Berger; Tobias Derfuss; Ralf Linker; Mathias Mäurer; Martin Stangel; Orhan Aktas; Karl Baum; Martin Berghoff; Stefan Bittner; Andrew Chan; Adam Czaplinski; Florian Deisenhammer; Franziska Di Pauli; Renaud Du Pasquier; Christian Enzinger; Elisabeth Fertl; Achim Gass; Klaus Gehring; Claudio Gobbi; Norbert Goebels; Michael Guger; Aiden Haghikia; Hans-Peter Hartung; Fedor Heidenreich; Olaf Hoffmann; Zoë R Hunter; Boris Kallmann; Christoph Kleinschnitz; Luisa Klotz; Verena Leussink; Fritz Leutmezer; Volker Limmroth; Jan D Lünemann; Andreas Lutterotti; Sven G Meuth; Uta Meyding-Lamadé; Michael Platten; Peter Rieckmann; Stephan Schmidt; Hayrettin Tumani; Martin S Weber; Frank Weber; Uwe K Zettl; Tjalf Ziemssen; Frauke Zipp Journal: Nervenarzt Date: 2021-07-23 Impact factor: 1.214
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Authors: Mathias Mäurer; Klaus Tiel-Wilck; Eckard Oehm; Nils Richter; Michael Springer; Patrick Oschmann; Arndt Manzel; Stefanie Hieke-Schulz; Vera Zingler; Julia A Kandenwein; Tjalf Ziemssen; Ralf A Linker Journal: Ther Adv Neurol Disord Date: 2019-12-19 Impact factor: 6.570
Authors: Marcello Moccia; Ilaria Loperto; Roberta Lanzillo; Antonio Capacchione; Antonio Carotenuto; Maria Triassi; Vincenzo Brescia Morra; Raffaele Palladino Journal: BMC Health Serv Res Date: 2020-08-26 Impact factor: 2.655
Authors: Bianca Weinstock-Guttman; Robert Bermel; Gary Cutter; Mark S Freedman; Thomas P Leist; Xiaoye Ma; Deidre Kile; Bruno Musch; Anthony T Reder; Jerry S Wolinsky Journal: Mult Scler Date: 2021-08-12 Impact factor: 6.312