Massimo Filippi1,2,3,4,5, Federica Esposito6,7, Miryam Cannizzaro6,7,8, Laura Ferré6,7,8, Ferdinando Clarelli7, Antonino Giordano6,7,8, Francesca Sangalli6, Bruno Colombo6, Giancarlo Comi8, Lucia Moiola6, Vittorio Martinelli6. 1. Neurology Unit, IRCCS San Raffaele Scientific Institute, Via Olgettina, 60, 20132, Milan, Italy. filippi.massimo@hsr.it. 2. Vita-Salute San Raffaele University, Via Olgettina, 60, 20132, Milan, Italy. filippi.massimo@hsr.it. 3. Neurorehabilitation Unit, IRCCS San Raffaele Scientific Institute, Via Olgettina, 60, 20132, Milan, Italy. filippi.massimo@hsr.it. 4. Neurophysiology Service, IRCCS San Raffaele Scientific Institute, Via Olgettina, 60, 20132, Milan, Italy. filippi.massimo@hsr.it. 5. Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Via Olgettina, 60, 20132, Milan, Italy. filippi.massimo@hsr.it. 6. Neurology Unit, IRCCS San Raffaele Scientific Institute, Via Olgettina, 60, 20132, Milan, Italy. 7. Laboratory of Human Genetics of Neurological Disorders, Institute of Experimental Neurology, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy. 8. Vita-Salute San Raffaele University, Via Olgettina, 60, 20132, Milan, Italy.
Abstract
BACKGROUND: Multiple sclerosis (MS) is a chronic autoimmune disease with huge heterogeneity in terms of clinical course, disease severity and treatment response. The need for a tailored treatment approach has emerged over the last few years. The present observational study aims to assess fingolimod (FTY) effectiveness in RRMS patients, stratifying them according to the disease-modifying treatments used before FTY, to identify subjects who could benefit more from this treatment. METHODS: We prospectively included 554 RRMS patients who started FTY at San Raffaele Hospital between 2012 and 2018. We classified them into three categories according to previous treatments: naïve patients, subjects previously treated with first-line drugs, and patients previously treated with second-line drugs. We compared disease activity during a 2-years follow-up using No-Evidence-of-Disease-Activity (NEDA-3) and Time-To-First-Relapse (TTFR) outcomes, applying logistic and Cox proportional hazard regression respectively. RESULTS: The proportion of patients who maintained NEDA-3 status was higher in the naïve group despite a higher level of baseline disease activity (naïve versus first-line p = 0.025, naïve versus second-line p < 0.001). In the multivariable analyses, patients switching to FTY from first- and second-line treatments showed a higher risk of disease reactivation (p = 0.041, OR = 1.86 and p = 0.002, OR = 2.92, respectively) and a shorter TTFR (p = 0.017, HR = 4.35 and p = 0.001, HR = 8.19, respectively). CONCLUSION: Naïve patients showed a better response to FTY compared to patients switching to FTY from other drugs. Our findings support the early use of FTY in patients with active MS.
BACKGROUND: Multiple sclerosis (MS) is a chronic autoimmune disease with huge heterogeneity in terms of clinical course, disease severity and treatment response. The need for a tailored treatment approach has emerged over the last few years. The present observational study aims to assess fingolimod (FTY) effectiveness in RRMS patients, stratifying them according to the disease-modifying treatments used before FTY, to identify subjects who could benefit more from this treatment. METHODS: We prospectively included 554 RRMS patients who started FTY at San Raffaele Hospital between 2012 and 2018. We classified them into three categories according to previous treatments: naïve patients, subjects previously treated with first-line drugs, and patients previously treated with second-line drugs. We compared disease activity during a 2-years follow-up using No-Evidence-of-Disease-Activity (NEDA-3) and Time-To-First-Relapse (TTFR) outcomes, applying logistic and Cox proportional hazard regression respectively. RESULTS: The proportion of patients who maintained NEDA-3 status was higher in the naïve group despite a higher level of baseline disease activity (naïve versus first-line p = 0.025, naïve versus second-line p < 0.001). In the multivariable analyses, patients switching to FTY from first- and second-line treatments showed a higher risk of disease reactivation (p = 0.041, OR = 1.86 and p = 0.002, OR = 2.92, respectively) and a shorter TTFR (p = 0.017, HR = 4.35 and p = 0.001, HR = 8.19, respectively). CONCLUSION: Naïve patients showed a better response to FTY compared to patients switching to FTY from other drugs. Our findings support the early use of FTY in patients with active MS.
Authors: Peter A Calabresi; Ernst-Wilhelm Radue; Douglas Goodin; Douglas Jeffery; Kottil W Rammohan; Anthony T Reder; Timothy Vollmer; Mark A Agius; Ludwig Kappos; Tracy Stites; Bingbing Li; Linda Cappiello; Philipp von Rosenstiel; Fred D Lublin Journal: Lancet Neurol Date: 2014-03-28 Impact factor: 44.182
Authors: F Esposito; L Ferrè; F Clarelli; M A Rocca; G Sferruzza; L Storelli; M Radaelli; F Sangalli; L Moiola; B Colombo; F Martinelli Boneschi; G Comi; M Filippi; V Martinelli Journal: J Neurol Date: 2018-02-12 Impact factor: 4.849
Authors: Ludwig Kappos; Ernst-Wilhelm Radue; Paul O'Connor; Chris Polman; Reinhard Hohlfeld; Peter Calabresi; Krzysztof Selmaj; Catherine Agoropoulou; Malgorzata Leyk; Lixin Zhang-Auberson; Pascale Burtin Journal: N Engl J Med Date: 2010-01-20 Impact factor: 91.245
Authors: Jeffrey A Cohen; Frederik Barkhof; Giancarlo Comi; Hans-Peter Hartung; Bhupendra O Khatri; Xavier Montalban; Jean Pelletier; Ruggero Capra; Paolo Gallo; Guillermo Izquierdo; Klaus Tiel-Wilck; Ana de Vera; James Jin; Tracy Stites; Stacy Wu; Shreeram Aradhye; Ludwig Kappos Journal: N Engl J Med Date: 2010-01-20 Impact factor: 91.245
Authors: C Zecca; S Roth; O Findling; G Perriard; V Bachmann; M L Pless; A Baumann; C P Kamm; P H Lalive; A Czaplinski Journal: Eur J Neurol Date: 2018-03-06 Impact factor: 6.089