Doriana Landi1, Alessio Signori2, Maria Cellerino3, Giuseppe Fenu4, Carolina Gabri Nicoletti1, Marta Ponzano2, Elisabetta Mancuso3, Marzia Fronza4, Maria Elena Ricchiuto1, Giacomo Boffa3, Matilde Inglese3,5, Girolama Alessandra Marfia1,6, Eleonora Cocco4, Jessica Frau7. 1. Multiple Sclerosis Clinical and Research Unit, Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy. 2. Department of Health Sciences, University of Genova, Genoa, Italy. 3. Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa, Genoa, Italy. 4. Multiple Sclerosis Centre, Binaghi Hospital, ATS Sardegna, University of Cagliari, Via Is Guadazzonis, 2, 09126, Cagliari, Italy. 5. IRCCS Ospedale Policlinico San Martino, Genoa, Italy. 6. Unit of Neurology, IRCCS Istituto Neurologico Mediterraneo NEUROMED, Pozzilli, IS, Italy. 7. Multiple Sclerosis Centre, Binaghi Hospital, ATS Sardegna, University of Cagliari, Via Is Guadazzonis, 2, 09126, Cagliari, Italy. jessicafrauneuro@gmail.com.
Abstract
OBJECTIVE: To analyse the course of multiple sclerosis (MS) after fingolimod withdrawal in a multicentre cohort. METHODS: Patients who discontinued fingolimod were included. Relapses, Expanded Disability Status Scale (EDSS), and new/gadolinium-enhancing lesions on magnetic resonance imaging (MRI) were assessed during the last year on fingolimod, and in the year after discontinuation. Wilcoxon test was used to analyse the difference in EDSS and relapses between the two periods, and to compare lymphocyte counts at discontinuation and 3 months later. Demographic and clinical variables were evaluated using univariable and multivariable logistic regression analyses. RESULTS: Patients were 230 (females 66.1%; mean age 38 years; median EDSS 3). Fingolimod was discontinued due to inefficacy in 57%, and 87.4% started another treatment. Relapse was observed in 33% of the patients in the year after discontinuation. Severe reactivation was observed in 15%. During the first 6 months after discontinuation, new/enhancing lesions were seen in 62/116 patients. Higher age at the fingolimod discontinuation was found to be associated with a lower probability of inflammatory activity (p = 0.001) and severe reactivation (p = 0.007) during the year after discontinuation. Lower lymphocyte count was a risk factor for clinical, radiological, and severe activity (p = 0.02, p = 0.002, p = 0.01, respectively). CONCLUSIONS: The main reason for the discontinuation of fingolimod was inefficacy. One-third of the patients had a relapse during the year after discontinuation, 15% experienced a severe reactivation, and approximately 50% of patients with available MRI scan had new/enhancing lesions. The risk factors for disease activity after discontinuation were low lymphocyte count and younger age.
OBJECTIVE: To analyse the course of multiple sclerosis (MS) after fingolimod withdrawal in a multicentre cohort. METHODS: Patients who discontinued fingolimod were included. Relapses, Expanded Disability Status Scale (EDSS), and new/gadolinium-enhancing lesions on magnetic resonance imaging (MRI) were assessed during the last year on fingolimod, and in the year after discontinuation. Wilcoxon test was used to analyse the difference in EDSS and relapses between the two periods, and to compare lymphocyte counts at discontinuation and 3 months later. Demographic and clinical variables were evaluated using univariable and multivariable logistic regression analyses. RESULTS: Patients were 230 (females 66.1%; mean age 38 years; median EDSS 3). Fingolimod was discontinued due to inefficacy in 57%, and 87.4% started another treatment. Relapse was observed in 33% of the patients in the year after discontinuation. Severe reactivation was observed in 15%. During the first 6 months after discontinuation, new/enhancing lesions were seen in 62/116 patients. Higher age at the fingolimod discontinuation was found to be associated with a lower probability of inflammatory activity (p = 0.001) and severe reactivation (p = 0.007) during the year after discontinuation. Lower lymphocyte count was a risk factor for clinical, radiological, and severe activity (p = 0.02, p = 0.002, p = 0.01, respectively). CONCLUSIONS: The main reason for the discontinuation of fingolimod was inefficacy. One-third of the patients had a relapse during the year after discontinuation, 15% experienced a severe reactivation, and approximately 50% of patients with available MRI scan had new/enhancing lesions. The risk factors for disease activity after discontinuation were low lymphocyte count and younger age.
Authors: Patrick Vermersch; Ernst-Wilhelm Radue; Norman Putzki; Shannon Ritter; Martin Merschhemke; Mark S Freedman Journal: Mult Scler J Exp Transl Clin Date: 2017-09-27
Authors: Niklas Frahm; Firas Fneish; David Ellenberger; Peter Flachenecker; Friedemann Paul; Clemens Warnke; Christoph Kleinschnitz; Tina Parciak; Dagmar Krefting; Kerstin Hellwig; Judith Haas; Paulus S Rommer; Alexander Stahmann; Uwe K Zettl Journal: Neurol Ther Date: 2022-01-12
Authors: Charles B Malpas; Izanne Roos; Sifat Sharmin; Katherine Buzzard; Olga Skibina; Helmut Butzkueven; Ludwig Kappos; Francesco Patti; Raed Alroughani; Dana Horakova; Eva Kubala Havrdova; Guillermo Izquierdo; Sara Eichau; Suzanne Hodgkinson; Pierre Grammond; Jeannette Lechner-Scott; Tomas Kalincik Journal: Clin Drug Investig Date: 2022-03-18 Impact factor: 2.859