Matteo Lucchini1,2, Luca Prosperini3, Maria Chiara Buscarinu4, Diego Centonze5,6, Antonella Conte6,7, Antonio Cortese7,8, Giorgia Elia9, Roberta Fantozzi6, Elisabetta Ferraro8, Claudio Gasperini3, Antonio Ianniello9, Doriana Landi5,10, Girolama Alessandra Marfia5,6,10, Viviana Nociti11,12, Carlo Pozzilli9,13, Marco Salvetti4,6, Carla Tortorella3, Massimiliano Mirabella11,12. 1. Multiple Sclerosis Center, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Largo Agostino Gemelli 8, 00168, Rome, Italy. lucchinimatteo87@gmail.com. 2. Università Cattolica del Sacro Cuore, Rome, Italy. lucchinimatteo87@gmail.com. 3. S. Camillo Forlanini Hospital, Rome, Italy. 4. Center for Experimental Neurological Therapies, NESMOS, S. Andrea Hospital, Rome, Italy. 5. Department of Systems Medicine, University of Rome "Tor Vergata", Rome, Italy. 6. IRCCS Neuromed, Pozzilli, Isernia, Italy. 7. Department of Human Neurosciences, Sapienza University, Rome, Italy. 8. San Filippo Neri Hospital, Rome, Italy. 9. Multiple Sclerosis Center, Ospedale S. Andrea, Rome, Italy. 10. Multiple Sclerosis Clinical and Research Unit, Fondazione Policlinico di Tor Vergata, Rome, Italy. 11. Multiple Sclerosis Center, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Largo Agostino Gemelli 8, 00168, Rome, Italy. 12. Università Cattolica del Sacro Cuore, Rome, Italy. 13. Department of Neurology and Psychiatry, Sapienza University, Rome, Italy.
Abstract
BACKGROUND: Dimethyl fumarate (DMF) is an oral drug approved for Relapsing Multiple Sclerosis (RMS) patients. Grade III lymphopenia is reported in 5-10% DMF-treated patients. Data on lymphocyte count (ALC) recovery after DMF withdrawal following prolonged lymphopenia are still scarce. OBJECTIVES: To characterize ALC recovery and to identify predictors of slower recovery after DMF interruption. METHODS: Multicenter data from RMS patients who started DMF and developed lymphopenia during treatment were collected. In patients with grade II-III lymphopenia, ALCs were evaluated from DMF withdrawal until reaching lymphocyte counts > 800/mm3. RESULTS: Among 1034 patients who started DMF, we found 198 (19.1%) patients with lymphopenia and 65 patients (6.3%) who discontinued DMF due to persistent grade II-III lymphopenia. Complete data were available for 51 patients. All patients recovered to ALC > 800 cells/mm3 with a median time of 3.4 months. Lower ALCs at DMF suspension (HR 0.98; p = 0.005), longer disease duration (HR 1.29; p = 0.014) and prior exposure to MS treatments (HR 0.03; p = 0.025) were found predictive of delayed ALC recovery. CONCLUSION: ALC recovery after DMF withdrawal is usually rapid, nevertheless it may require longer time in patients with lower ALC count at DMF interruption, longer disease duration and previous exposure to MS treatments, potentially leading to delayed initiation of a new therapy.
BACKGROUND:Dimethyl fumarate (DMF) is an oral drug approved for Relapsing Multiple Sclerosis (RMS) patients. Grade III lymphopenia is reported in 5-10% DMF-treated patients. Data on lymphocyte count (ALC) recovery after DMF withdrawal following prolonged lymphopenia are still scarce. OBJECTIVES: To characterize ALC recovery and to identify predictors of slower recovery after DMF interruption. METHODS: Multicenter data from RMS patients who started DMF and developed lymphopenia during treatment were collected. In patients with grade II-III lymphopenia, ALCs were evaluated from DMF withdrawal until reaching lymphocyte counts > 800/mm3. RESULTS: Among 1034 patients who started DMF, we found 198 (19.1%) patients with lymphopenia and 65 patients (6.3%) who discontinued DMF due to persistent grade II-III lymphopenia. Complete data were available for 51 patients. All patients recovered to ALC > 800 cells/mm3 with a median time of 3.4 months. Lower ALCs at DMF suspension (HR 0.98; p = 0.005), longer disease duration (HR 1.29; p = 0.014) and prior exposure to MS treatments (HR 0.03; p = 0.025) were found predictive of delayed ALC recovery. CONCLUSION:ALC recovery after DMF withdrawal is usually rapid, nevertheless it may require longer time in patients with lower ALC count at DMF interruption, longer disease duration and previous exposure to MS treatments, potentially leading to delayed initiation of a new therapy.
Entities:
Keywords:
Dimethyl fumarate; Lymphopenia; Multiple sclerosis; Real-world study
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