We Know How To Prescribe Natalizumab For Multiple Sclerosis, But Do We Know How To Withdraw It?

Natalizumab is a potent immunosuppressive monoclonal antibody used for the treatment of multiple sclerosis (MS). While definite guidelines for the safety of natalizumab prescriptions are available in all countries, there are no specific recommendations on how to withdraw the drug if the need arises. There are reports describing MS complications after natalizumab infusions were stopped. Most neurologists seem to stop natalizumab treatment according to their idea on how to best carry out the withdrawal. The present study shows the very different manners in which expert neurologists from 14 MS units in Brazil stopped natalizumab in their patients. The authors concluded that pharmacovigilance on natalizumab must persist after the drug is withdrawn in order to have enough data for adequate recommendations. © 2014 Informa UK, Ltd.142127130Nylander, A., Hafler, D.A., Multiple sclerosis (2012) J Clin Invest, 122, pp. 1180-1188McCoyd, M., Update on therapeutic options for multiple sclerosis (2013) Neurol Clin, 31, pp. 827-845McCormack, P.L., Natalizumab: A review of its use in the management of relapsing-remitting multiple sclerosis (2013) Drugs, 73 (13), pp. 1463-1481Fernández, O., Best practice in the use of natalizumab in multiple sclerosis (2013) Ther Adv Neurol Disord, 6, pp. 69-79Sørensen, P.S., Bertolotto, A., Edan, G., Risk stratification for progressive multifocal leukoencephalopathy in patients treated with natalizumab (2012) Mult Scler, 18, pp. 143-152Pucci, E., Giuliani, G., Solari, A., Natalizumab for relapsing remitting multiple sclerosis (2011) Cochrane Database Syst Rev, 10, pp. CD007621Fragoso, Y.D., Alves-Leon, S.V., Arruda, W.O., Natalizumab adverse events are rare in patients with multiple sclerosis (2013) Arq Neuropsiquiatr, 71, pp. 137-141Damasceno, A., Von Glehn, F., Martinez, A.R., Early onset of natalizumab-related progressive multifocal leukoencephalopathy (2011) Mult Scler, 17, pp. 1397-1398Baumgartner, A., Stich, O., Rauer, S., Clinical and radiological disease reactivation after cessation of long-Term therapy with natalizumab (2012) Int J Neurosci, 122, pp. 35-39Rigau, V., Mania, A., Béfort, P., Lethal multiple sclerosis relapse after natalizumab withdrawal (2012) Neurology, 79, pp. 2214-2216Marousi, S., Travasarou, M., Karageorgiou, C.E., Simultaneous PML-IRIS after discontinuation of natalizumab in a patient with MS (2012) Neurology, 79, p. 2160Berger, J.R., Centonze, D., Comi, G., Considerations on discontinuing natalizumab for the treatment of multiple sclerosis (2010) Ann Neurol, 68, pp. 409-411Miravalle, A., Jensen, R., Kinkel, R.P., Immune reconstitution inflammatory syndrome in patients with multiple sclerosis following cessation of natalizumab therapy (2011) Arch Neurol, 68, pp. 186-191Borriello, G., Prosperini, L., Marinelli, F., Observations during an elective interruption of natalizumab treatment: A post-marketing study (2011) Mult Scler, 17, pp. 372-375Papeix, C., Depaz, R., Tourbah, A., Dramatic worsening following plasma exchange in severe post-natalizumab withdrawal multiple sclerosis relapse (2011) Mult Scler, 17, pp. 1520-1522Borriello, G., Prosperini, L., Mancinelli, C., Pulse monthly steroids during an elective interruption of natalizumab: A post-marketing study (2012) Eur J Neurol, 19, pp. 783-787Magraner, M.J., Coret, F., Navarré, A., Pulsed steroids followed by glatiramer acetate to prevent inflammatory activity after cessation of natalizumab therapy: A prospective, 6-month observational study (2011) J Neurol, 258, pp. 1805-1811Rossi, S., Motta, C., Studer, V., Effect of glatiramer acetate on disease reactivation in MS patients discontinuing natalizumab (2013) Eur J Neurol, 20, pp. 87-94Havla, J., Gerdes, L.A., Meinl, I., De-escalation from natalizumab in multiple sclerosis: Recurrence of disease activity despite switching to glatiramer acetate (2011) J Neurol, 258, pp. 1665-1669Gobbi, C., Meier, D.S., Cotton, F., Interferon beta 1b following natalizumab discontinuation: One year, randomized, prospective, pilot trial (2013) BMC Neurol, 13, p. 101Cree, B., De Seze, J., Fox, R., RESTORE Study: Effects of a 24-week natalizumab treatment interruption on immune parameters and multiple sclerosis magnetic resonance imaging disease activity 2012P06.168 (2012) Neurology, (78), pp. 106-168. , Meeting Abstracts 1Comi, G., Gold, R., Dahlke, F., Overall safety and relapse outcomes in fingolimod-Treated patients previously treated with natalizumab in the 4-month open-label first study [poster (2013) European Neurology Society (ENS) Meeting Barcelona SpainHavla, J., Tackenberg, B., Hellwig, K., Fingolimod reduces recurrence of disease activity after natalizumab withdrawal in multiple sclerosis (2013) J Neurol, 260, pp. 1382-1387Daelman, L., Maitrot, A., Maarouf, A., Severe multiple sclerosis reactivation under fingolimod 3 months after natalizumab withdrawal (2012) Mult Scler, 11, pp. 1647-1649Sempere, A.P., Martín-Medina, P., Berenguer-Ruiz, L., Switching from natalizumab to fingolimod: An observational study (2013) Acta Neurol Scand, 128, pp. e6-e10Centonze, D., Rossi, S., Rinaldi, F., Gallo, P., Severe relapses under fingolimod treatment prescribed after natalizumab (2012) Neurology, 79, pp. 2004-2005Jander, S., Turowski, B., Kieseier, B.C., Hartung, H.P., Emerging tumefactive multiple sclerosis after switching therapy from natalizumab to fingolimod (2012) Mult Scler, 18, pp. 1650-165

The Real-life Experience With Cardiovascular Complications In The First Dose Of Fingolimod For Multiple Sclerosis [a Experiência Da Vida Real Com Complicações Cardiovasculares Na Primeira Dose De Fingolimode]

Fingolimod is a new and efficient treatment for multiple sclerosis (MS). The drug administration requires special attention to the first dose, since cardiovascular adverse events can be observed during the initial six hours of fingolimod ingestion. The present study consisted of a review of cardiovascular data on 180 patients with MS receiving the first dose of fingolimod. The rate of bradycardia in these patients was higher than that observed in clinical trials with very strict inclusion criteria for patients. There were less than 10% of cases requiring special attention, but no fatal cases. All but one patient continued the treatment after this initial dose. This is the first report on real-life administration of fingolimod to Brazilian patients with MS, and one of the few studies with these characteristics in the world.729712714Thomas, K., Ziemssen, T., Management of fingolimod in clinical practice (2013) Clin Neurol Neurosurg., 115, pp. S60-S64Ontaneda, D., Hara-Cleaver, C., Rudick, R.A., Cohen, J.A., Bermel, R.A., Early tolerability and safety of fingolimod in clinical practice (2012) J Neurol Sci., 323, pp. 167-172Bünemann, M., Liliom, K., Brandts, B.K., A novel membrane receptor with high affinity for lysosphingomyelin and sphingosine 1-phosphate in atrial myocytes (1996) EMBO J., 15, pp. 5527-5534Sanna, M., Liao, J., Jo, E., Sphingosine 1-phosphate (S1P) receptor subtypes S1P1 and S1P3, respectively, regulate lymphocyte recirculation and heart rate (2004) J Biol Chem, 279, pp. 13839-13848Laroni, A., Brogi, D., Morra, V.B., Safety of the first dose of fingolimod for multiple sclerosis: Results of an open-label clinical trial (2014) BMC Neurol, 14, p. 65Polman, C.H.R., Reingold, S.C., Banwell, B., Dianosticcriteria for multiple sclerosis: 2010 Revisions to the Mac Donald criteria (2011) Ann Neurol, 69, pp. 292-302Espinosa, P.S., Berger, J.R., Delayed fingolimod-associated asystole (2011) Mult Scler, 17, pp. 1387-1389Kappos, L., Radue, E.W., O'Connor, P., A placebo-controlled trial of oral fingolimod in relapsing multiple sclerosis (2010) N Engl J Med, 362, pp. 387-401Singer, B.A., Initiating oral fingolimod treatment in patients with multiple sclerosis (2013) Ther Adv Neurol Disord, 6, pp. 269-27

The extrapituitary prolactin promoter polymorphism is associated with rheumatoid arthritis and anti-CCP antibodies in Mexican population

Background and objective: Women with multiple sclerosis (MS) who intend to get pregnant are often advised to discontinue disease modifying therapy (DMT) prior to conception. This recommendation is not based on medical evidence and may interfere with disease control by immunomodulatory drugs. The present study was designed to help discuss the effect of DMT for MS on pregnancy and on disease course. Patients and methods: Retrospective data from 152 pregnancies of 132 women with MS were collected by the physician in charge of the case. All data were entered into a specific file for qualitative and quantitative statistical analysis. Results: From the total group of patients, 89 pregnancies occurred without any exposure to MS drugs, while 61 pregnancies occurred with at least eight weeks of exposure to MS immunomodulatory drugs. The rate of obstetric and neonatal complications was similar in both groups, except for the newborn weight and height which was smaller for mothers receiving medications. Mothers' post-delivery relapse rate and EDSS scores in the follow-up period were significantly higher in the absence of treatment. Conclusion: It is possible that, with further such supportive data, international guidelines on MS treatment in young women who intend to get pregnant may need to be revised. " 2012 Elsevier B.V.",,,,,,"10.1016/j.clineuro.2012.04.024",,,"http://hdl.handle.net/20.500.12104/45105","http://www.scopus.com/inward/record.url?eid=2-s2.0-84872295057&partnerID=40&md5=c20df0b7feedea45f4a1222a90afb6b2",,,,,,"2",,"Clinical Neurology and Neurosurgery",,"15

The effects of long-term exposure to disease-modifying drugs during pregnancy in multiple sclerosis

Background and objective: Women with multiple sclerosis (MS) who intend to get pregnant are often advised to discontinue disease modifying therapy (DMT) prior to conception. This recommendation is not based on medical evidence and may interfere with disease control by immunomodulatory drugs. The present study was designed to help discuss the effect of DMT for MS on pregnancy and on disease course. Patients and methods: Retrospective data from 152 pregnancies of 132 women with MS were collected by the physician in charge of the case. All data were entered into a specific file for qualitative and quantitative statistical analysis. Results: From the total group of patients, 89 pregnancies occurred without any exposure to MS drugs, while 61 pregnancies occurred with at least eight weeks of exposure to MS immunomodulatory drugs. The rate of obstetric and neonatal complications was similar in both groups, except for the newborn weight and height which was smaller for mothers receiving medications. Mothers' post-delivery relapse rate and EDSS scores in the follow-up period were significantly higher in the absence of treatment. Conclusion: It is possible that, with further such supportive data, international guidelines on MS treatment in young women who intend to get pregnant may need to be revised. © 2012 Elsevier B.V

Multiple Sclerosis In South America: Month Of Birth In Different Latitudes Does Not Seem To Interfere With The Prevalence Or Progression Of The Disease [esclerose Múltipla Na América Do Sul: Mês De Nascimento Em Diferentes Latitudes Não Parece Interferir Com A Prevalência Ou Progressão Da Doença]

Objective: To assess whether the month of birth in different latitudes of South America might influence the presence or severity of multiple sclerosis (MS) later in life. Methods: Neurologists in four South American countries working at MS units collected data on their patients' month of birth, gender, age, and disease progression. Results: Analysis of data from 1207 MS patients and 1207 control subjects did not show any significant variation in the month of birth regarding the prevalence of MS in four latitude bands (0-10; 11-20; 21-30; and 31-40 degrees). There was no relationship between the month of birth and the severity of disease in each latitude band. Conclusion: The results from this study show that MS patients born to mothers who were pregnant at different Southern latitudes do not follow the seasonal pattern observed at high Northern latitudes.719:00 AM573579Templer, D.I., Trent, N.H., Spencer, D.A., Season of birth in multiple sclerosis (1992) Acta Neurol Scand, 85, pp. 107-109Bharanidharan, P., Monthly distribution of multiple sclerosis patients' births (1997) Int J Biometeorol, 40, pp. 117-118Salemi, G., Ragonese, P., Aridon, P., Is season of birth associated with multiple sclerosis? (2000) Acta Neurol Scand, 101, pp. 381-383Salzer, J., Svenningsson, A., Sundström, P., Season of birth and multiple sclerosis in Sweden (2010) Acta Neurol Scand, 122, pp. 70-73Bayes, H.K., Weir, C.J., O'Leary, C., Timing of birth and risk of multiple sclerosis in the Scottish population (2010) Eur Neur, 63, pp. 36-40Saastamoinen, K.P., Auvinen, M.K., Tienari, P.J., Month of birth is associated with multiple sclerosis but not with HLA-DR15 in Finland (2012) Mult Scler, 18, pp. 563-568Fernandes de Abreu, D.A., Babron, M.C., Rebeix, I., Season of birth and not vitamin D receptor promoter polymorphisms is a risk factor for multiple sclerosis (2009) Mult Scler, 15, pp. 1146-1152Willer, C.J., Dyment, D.A., Sadovnick, A.D., Timing of birth and risk of multiple sclerosis: Population based study (2005) BMJ, 330, p. 120. , Canadian Collaborative Study GroupDeussing, E.C., Jankosky, C.J., Clark, L.L., Estimated incidence of multiple sclerosis among United States Armed Forces personnel using the Defense Medical Surveillance System (2012) Mil Med, 177, pp. 594-600Staples, J., Ponsonby, A.L., Lim, L., Low maternal exposure to ultraviolet radiation in pregnancy, month of birth, and risk of multiple sclerosis in offspring: Longitudinal analysis (2010) BMJ, 340, p. 1640Givon, U., Zeilig, G., Dolev, M., The month of birth and the incidence of multiple sclerosis in the Israeli population (2012) Neuroepidemiology, 38, pp. 64-68Fragoso, Y.D., Shearer, K.D., Adoni, T., Month of birth does not seem to interfere with the development of multiple sclerosis later in life in Brazilian patients (2012) Neuroepidemiology, 39, pp. 70-71Koch, M., de Keyser, J., Tremlett, H., Timing of birth and disease progression in multiple sclerosis (2008) Mult Scler, 14, pp. 793-798Tremlett, H.L., Devonshire, V.A., Does the season or month of birth influence disease progression in multiple sclerosis? (2006) Neuroepidemiology, 26, pp. 195-198Poser, C.M., Paty, D.W., Scheinberg, L., New diagnostic criteria for multiple sclerosis: Guidelines for research protocols (1983) Ann Neurol, 13, pp. 227-231McDonald, W.I., Compston, A., Edan, G., Recommended diagnostic criteria for multiple sclerosis: Guidelines from the International Panel on the diagnosis of multiple sclerosis (2001) Ann Neurol, 50, pp. 121-127Polman, C.H., Reingold, S.C., Edan, G., Diagnostic criteria for multiple sclerosis: 2005 revisions to the "McDonald Criteria" (2005) Ann Neurol, 58, pp. 840-846Kurtzke, J.F., Rating neurologic impairment in multiple sclerosis: An expanded disability status scale (EDSS) (1983) Neurology (Cleveland), 33, pp. 1444-1452Damasceno, A., von Glehn, F., de Deus-Silva, L., Monthly variation of multiple sclerosis activity in the Southern hemisphere: Analysis from 996 relapses in Brazil (2012) Eur J Neurol, 19, pp. 660-662Altmann, D.M., Review series on helminths, immune modulation and the hygiene hypothesis: Nematode coevolution with adaptive immunity, regulatory networks and the growth of inflammatory diseases (2009) Immunology, 126, pp. 1-2Correale, J., Farez, M.F., The impact of environmental infections (parasites) on MS activity (2011) Mult Scler, 17, pp. 1162-1169Watson, P.E., McDonald, B.W., Seasonal variation of nutrient intake in pregnancy: Effects on infant measures and possible influence on diseases related to season of birth (2007) Eur J Clin Nutr, 61, pp. 1271-1280Melcon, M., Melcon, C., Bartoloni, L., Towards establishing MS prevalence in Latin America and the Caribbean (2013) Mult Scler, 19, pp. 145-152. , The "Grupo Colaborativo Multicéntrico para el Estudio de la Esclerosis Multiple en America Latina y el Caribe" (GEEMAL)Taylor, B.V., Pearson, J.F., Clarke, G., MS prevalence in New Zealand, an ethnically and latitudinally diverse country (2010) Mult Scler, 16, pp. 1422-1431Dobson, R., Giovannoni, G., Ramagopalan, S., The month of birth effect in multiple sclerosis: Systematic review, meta-analysis and effect of latitude (2013) J Neurol Neurosurg Psychiatry, 84, pp. 427-43