D Ferraro1,2, P Iaffaldano3, T Guerra3, M Inglese4,5, M Capobianco6, V Brescia Morra7, M Zaffaroni8, M Mirabella9,10, G Lus11, F Patti12,13, P Cavalla14, M Cellerino4, S Malucchi6, E Pisano7, F Vitetta15, D Paolicelli3, P Sola15, M Trojano3. 1. Neurology Unit, Azienda Ospedaliero-Universitaria of Modena, Modena, Italy. diana.ferraro@unimore.it. 2. Department of Biomedical, Metabolic and Neurosciences, University of Modena and Reggio Emilia, Via Pietro Giardini 1355, 41126, Modena, Italy. diana.ferraro@unimore.it. 3. Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari "Aldo Moro", Policlinico, Bari, Italy. 4. Department of Neuroscience, Rehabilitation, Maternal and Child Health (DINOGMI), University of Genoa, Genoa, Italy. 5. Ospedale Policlinico San Martino-IRCCS, Genoa, Italy. 6. Regional Referral MS Center, Neurological Unit, University Hospital San Luigi, Orbassano, Italy. 7. MS Center-AOU Policlinico Federico II, Naples, Italy. 8. Multiple Sclerosis Center, Gallarate Hospital, ASST Della Valle Olona, Gallarate, Italy. 9. Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy. 10. Università Cattolica del Sacro Cuore, Rome, Italy. 11. MS Center, II Division of Neurology, Univ. Della Campania "L. Vanvitelli", Naples, Italy. 12. Multiple Sclerosis Centre, AOU Policlinico "G. Rodolico", Catania, Italy. 13. Department of Medical and Surgical and Advanced Technologies, GF Ingrassia, University of Catania, Catania, Italy. 14. MS Centre, I Division of Neurology, City of Health and Science Turin Univ. Hospital, Turin, Italy. 15. Neurology Unit, Azienda Ospedaliero-Universitaria of Modena, Modena, Italy.
Abstract
BACKGROUND: Fingolimod (FTY) induces sequestration of lymphocytes in secondary lymphoid organs and the average lymphocyte recovery following discontinuation takes 1-2 months. It has been hypothesized that the therapeutic effects of subsequent cell-depleting agents may be compromised if initiated before lymphocyte recovery has occurred. OBJECTIVE: To assess the risk of relapses following FTY discontinuation and the initiation of a B/T cell-depleting agent in relation to washout duration using data from the Italian MS Register. METHODS: The risk of relapses was assessed in relation to different washout durations (< 6, 6-11, 12-17 and > / = 18 weeks) in patients starting alemtuzumab, rituximab, ocrelizumab or cladribine following FTY discontinuation. RESULTS: We included 329 patients in the analysis (226F, 103 M; mean age 41 ± 10 years). During the cell-depleting treatment, the incidence rate ratio for a relapse was significantly greater in patients with a washout period of 12-17 and > / = 18 weeks compared to the reference period (< 6 weeks). The risk of a relapse was significantly influenced by the occurrence of relapses during FTY treatment and by washout length, with hazard ratios markedly increasing with the washout duration. CONCLUSION: The risk of relapses increases with the washout duration when switching from FTY to lymphocyte-depleting agents.
BACKGROUND: Fingolimod (FTY) induces sequestration of lymphocytes in secondary lymphoid organs and the average lymphocyte recovery following discontinuation takes 1-2 months. It has been hypothesized that the therapeutic effects of subsequent cell-depleting agents may be compromised if initiated before lymphocyte recovery has occurred. OBJECTIVE: To assess the risk of relapses following FTY discontinuation and the initiation of a B/T cell-depleting agent in relation to washout duration using data from the Italian MS Register. METHODS: The risk of relapses was assessed in relation to different washout durations (< 6, 6-11, 12-17 and > / = 18 weeks) in patients starting alemtuzumab, rituximab, ocrelizumab or cladribine following FTY discontinuation. RESULTS: We included 329 patients in the analysis (226F, 103 M; mean age 41 ± 10 years). During the cell-depleting treatment, the incidence rate ratio for a relapse was significantly greater in patients with a washout period of 12-17 and > / = 18 weeks compared to the reference period (< 6 weeks). The risk of a relapse was significantly influenced by the occurrence of relapses during FTY treatment and by washout length, with hazard ratios markedly increasing with the washout duration. CONCLUSION: The risk of relapses increases with the washout duration when switching from FTY to lymphocyte-depleting agents.
Authors: Trina A Johnson; Igor Shames; Mark Keezer; Yves Lapierre; David G Haegert; Amit Bar-Or; Jack Antel Journal: Clin Immunol Date: 2010-10 Impact factor: 3.969
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