Resumen
La esclerosis múltiple es la condición desmielinizante que afecta con mayor frecuencia el sistema nervioso central (SNC). Se considera una enfermedad de alto costo y una de las principales causas de discapacidad neurológica en adultos jóvenes. A pesar de los avances logrados en su diagnóstico y tratamiento, algunos aspectos continúan siendo controversiales. En este manuscrito se discuten 15 puntos polémicos, reconocidos en la práctica clínica diaria y la investigación de sujetos con EM. Para analizar el contexto de cada controversia con la mejor evidencia disponible, se realizó una revisión sistemática de la literatura disponible en MEDLINE, Embase, Cochrane y LILACS. Los temas incluyen la interrupción del tratamiento inmunomodulador, la utilidad de las bandas oligoclonales, el cambio a fármacos de segunda línea, las indicaciones de seguimiento con resonancia magnética, la plasmaféresis, el síndrome radiológico aislado, el manejo ambulatorio de las recaídas, la duración óptima de los ciclos de corticoides intravenosos, el beneficios de la tomografía de coherencia óptica, la deficiencia de vitamina D, el manejo de la EM secundariamente progresiva, los nuevos medicamentos orales y la seguridad del uso de interferón durante el embarazo. En el marco de cada controversia, se plantean recomendaciones específicas y conclusiones que pueden ser de utilidad para futuras investigaciones.
Citas
RAMAGOPALAN SV, DOBSON R, MEIER UC, GIOVANNONI G. Multiple sclerosis: risk factors, prodromes, and potential causal pathways. Lancet Neurol. 2010; 9:727-39.
COURTNEY AM, TREADAWAY K, REMINGTON G, FROHMAN E. Multiple sclerosis. Med Clin North Am. 2009; 93:451-76.
TORO J, CARDENAS S, MARTINEZ CF, URRUTIA J, DIAZ C. Multiple sclerosis in Colombia and other Latin American Countries. Mult Scler Relat Disord. 2013; 2;80-9.
KATZ SAND IB, LUBLIN FD. Diagnosis and differential diagnosis of multiple sclerosis. Continuum. 2013; 19:922-43.
COMPSTON A, COLES A. Multiple sclerosis. Lancet. 2008; 372:1502-17.
ROVARIS M, CONFAVREUX C, FURLAN R, KAPPOS L, COMI G, FILIPPI M. Secondary progressive multiple sclerosis: current knowledge and future challenges. Lancet Neurol. 2006; 5:343-54.
MILLER DH, LEARY SM. Primary-progressive multiple sclerosis. Lancet Neurol. 2007; 6:903-12.
BISCHOFF C, SCHREIBER H, BERGMANN A. Background information on multiple sclerosis patients stopping ongoing immunomodulatory therapy: a multicenter study in a community-based environment. J Neurol. 2012; 259:2347-53.
SIGER M, DURKO A, NICPAN A, KONARSKA M, GRUDZIECKA M, SELMAJ K. Discontinuation of interferon beta therapy in multiple sclerosis patients with high pre-treatment disease activity leads to prompt return to previous disease activity. J Neurol Sci. 2011; 303:50-2.
RICHERT DN, ZIERAK MC, BASH CN, LEWIS BK, MCFARLAND HF, FRANK JA. MRI and clinical activity in MS patients after terminating treatment with interferon beta 1b. Mult Scler. 2000; 6:86-90.
WU X, DASTIDAR P, KUUSISTO P, UKKONEN M, HUHTALA H, ELOVAARA I. Increased disability and MRI lesions after discontinuation of IFN-beta- 1a in secondary progressive MS. Acta Neurol Scand. 2005; 112:242-7.
O’CONNOR PW, GOODMAN A, KAPPOS L, LUBLIN FD, MILLER DH, POLMAN C, et al. Disease activity return during natalizumab treatment interruption in patients with multiple sclerosis. Neurology. 2011; 76:1858-65.
MIRAVALLE A, JENSEN R, KINKEL RP. Immune reconstitution inflammatory syndrome in patients with multiple sclerosis following cessation of natalizumab therapy. Arch Neurol. 2011; 68:186-91.
HAKIKI B, PORTACCIO E, GIANNINI M, RAZZOLINI L, PASTÒ L, AMATO MP. Withdrawal of fingolimod treatment for relapsing-remitting multiple sclerosis: report of six cases. Mult Scler. 2012; 18:1636-9.
COYLE PK. Switching therapies in multiple sclerosis. CNS Drugs. 2013; 27:239-47.
GOBBI C, MEIER DS, COTTON F, SINTZEL M, LEPPERT D, GUTTMANN CR, et al. Interferon beta 1b following natalizumab discontinuation: one year, randomized, prospective, pilot trial. BMC Neurol. 2013; 13:101.
HAVLA J, GERDES LA, MEINL I, KRUMBHOLZ M, FABER H, WEBER F, et al. De-escalation from natalizumab in multiple sclerosis: recurrence of disease activity despite switching to glatiramer acetate. J Neurol. 2011; 258:1665-9.
RIECKMANN P, HEIDENREICH F, SAILER M, ZETTL UK, ZESSACK N, HARTUNG HP, et al. Treatment de-escalation after mitoxantrone therapy: results of a phase IV, multicentre, open-label, randomized study of subcutaneous interferon beta-1a in patients with relapsing multiple sclerosis. Ther Adv Neurol Disord. 2012; 5:3-12.
POZZILLI C, BRUNETTI M, AMICOSANTE AM, GASPERINI C, RISTORI G, PALMISANO L, et al. Home based management in multiple sclerosis: results of a randomised controlled trial. J Neurol Neurosurg Psychiatry. 2002; 73:250-5.
CHATAWAY J, PORTER B, RIAZI A, HEANEY D, WATT H, HOBART J, ET AL. Home versus outpatient administration of intravenous steroids for multiple-sclerosis relapses: a randomised controlled trial. Lancet Neurol. 2006;5:565-71.
ROMERO M, ARANGO C. ALVIS N, SUÁREZ JC, DUQUE. A. Costos de la Esclerosis Múltiple en Colombia. Value Health. 2011;14 (5 suppl1):548-50.
ROBSON LS, BAIN C, BECK S, GUTHRIE S, COYTE PC, O’CONNOR P. Cost analysis of methylprednisolone treatment of multiple sclerosis patients. Can J Neurol Sci. 1998; 25:222-9.
CRÉANGE A, DEBOUVERIE M, JAILLONRIVIÈRE V, TAITHE F, LIBAN D, MOUTEREAU
A, et al. Home administration of intravenous methylprednisolone for multiple sclerosis relapses: the experience of French multiple sclerosis networks. Mult Scler. 2009; 15:1085-91.
ROVIRA A, AUGER C, ALONSO J. Magnetic resonance monitoring of lesion evolution in multiple sclerosis. Ther Adv Neurol Disord. 2013;6:298-310.
FILIPPI M, ROCCA MA. MR imaging of multiple sclerosis. Radiology. 2011; 259:659-81.
CARRÁ A, MACÍAS-ISLAS MÁ, GABBAI AA, CORREALE J, BOLAÑA C, SOTELO ED, et al. Optimizing outcomes in multiple sclerosis: consensus guidelines for the diagnosis and treatment of multiple sclerosis in Latin America. Ther Adv Neurol Disord. 2011; 4:349-60.
SIMON JH, LI D, TRABOULSEE A, COYLE PK, ARNOLD DL, BARKHOF F, et al. Standardized MR imaging protocol for multiple sclerosis: Consortium of MS Centers consensus guidelines. AJNR Am J Neuroradiol. 2006; 27:455-61.
ROVIRA A, TINTORÉ M, ALVAREZ-CERMEÑO JC, IZQUIERDO G, PRIETO JM. Recommendations for using and interpreting magnetic resonance imaging in multiple sclerosis. Neurología. 2010; 25:248-65.
THE CONSORTIUM OF MULTIPLE SCLEROSIS CENTERS. Consortium of MS Centres MRI Protocol for the Diagnosis and Follow-Up of MS. 2009 revised guidelines. 2009 [Actualizado 2012 Nov 10; Citado 2013 Sep 20]. Disponible en: http://c.ymcdn.com/sites/www.mscare.org/resource/collection/9C5F19B9-3489-48B0-A54B-623A1ECEE07B/mriprotocol2009.pdf
PROSPERINI L, MANCINELLI CR, DE GIGLIO L, DE ANGELIS F, BARLETTA V, POZZILLI C. Interferon beta failure predicted by EMA criteria or isolated MRI activity in multiple sclerosis. Mult Scler. 2013 Sep 3. Artículo en prensa
KLAWITER EC. Current and new directions in MRI in multiple sclerosis. Continuum. 2013;19:1058- 73.
KAPPOS L, BATES D, EDAN G, ERAKSOY M, GARCIA-MERINO A, GRIGORIADIS N, et al. Natalizumab treatment for multiple sclerosis:
updated recommendations for patient selection and monitoring. Lancet Neurol. 2011; 10:745-58.
AKSAMIT AJ. Review of progressive multifocal leukoencephalopathy and natalizumab. Neurologist. 2006; 12:293-8.
BLOOMGREN G, RICHMAN S, HOTERMANS C, SUBRAMANYAM M, GOELZ S, NATARAJAN A, et al. Risk of natalizumab-associated progressive multifocal leukoencephalopathy. N Engl J Med. 2012; 366:1870-80.
PUCCI E, GIULIANI G, SOLARI A, SIMI S, MINOZZI S, DI PIETRANTONJ C, et al. Natalizumab for relapsing remitting multiple sclerosis. Cochrane Database Syst Rev. 2011;(10):CD007621.
POLMAN CH, REINGOLD SC, BANWELL B, CLANET M, COHEN JA, FILIPPI M, et al. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol. 2011; 69:292-302.
SANDBERG-WOLLHEIM M, OLSSON T. Cerebrospinal fluid oligoclonal bands are important in the diagnosis of multiple sclerosis, unreasonably downplayed by the McDonald criteria 2010: Yes. Mult Scler. 2013; 19:714-6.
DOBSON R, RAMAGOPALAN S, DAVIS A, GIOVANNONI G. Cerebrospinal fluid oligoclonal bands in multiple sclerosis and clinically isolated syndromes: a meta-analysis of prevalence, prognosis and effect of latitude. J Neurol Neurosurg Psychiatry. 2013; 84:909-14.
JARIUS S, PAUL F, FRANCIOTTA D, RUPRECHT K, RINGELSTEIN M, BERGAMASCHI R, et al. Cerebrospinal fluid findings in aquaporin-4 antibody positive neuromyelitis optica: results from 211 lumbar punctures. J Neurol Sci. 2011; 306:82-90.
DALE RC, SOUSA C, CHONG WK, COX TC, HARDING B, NEVILLE BG. Acute disseminated encephalomyelitis, multiphasic disseminated encephalomyelitis and multiple sclerosis in children. Brain. 2000; 123:2407-22.
TINTORÉ M, ROVIRA A, RÍO J, TUR C, PELAYO R, NOS C, ET AL. Do oligoclonal bands add information to MRI in first attacks of multiple sclerosis? Neurology. 2008; 70:1079-83.
FERRARO D, SIMONE AM, BEDIN R, GALLI V, VITETTA F, FEDERZONI L. Cerebrospinal fluid oligoclonal IgM bands predict early conversion to clinically definite multiple sclerosis in patients with Clinically Isolated Syndrome. J Neuroimmunol. 2013; 257:76-81.
FREEDMAN MS, THOMPSON EJ, DEISENHAMMER F, GIOVANNONI G, GRIMSLEY G, KEIR G, et al. Recommended standard of cerebrospinal
fluid analysis in the diagnosis of multiple sclerosis: a consensus statement. Arch Neurol. 2005; 62:865-70.
FORTINI AS, SANDERS EL, WEINSHENKER BG, KATZMANN JA. Cerebrospinal fluid oligoclonal bands in the diagnosis of multiple sclerosis. Isoelectric focusing with IgG immunoblotting compared with high-resolution agarose gel electrophoresis and cerebrospinal fluid IgG index. Am J Clin Pathol. 2003; 120:672-5.
LUNDING J,MIDGARD R, VEDELER CA. Oligoclonal bands in cerebrospinal Fluid: a comparative study of isoelectric focusing, agarose gel electrophoresis and IgG index. Acta Neurol Scand. 2000: 102:322-5.
CABRERA-LIMPIAS S, GONZÁLEZ JC, ROMERO-SÁNCHEZ C, CENTANARO G, VERGARA JP. Bandas oligoclonales en líquido cefalorraquídeo
de pacientes con esclerosis múltiple del Hospital Militar Central, Bogotá DC. Acta Neurol Colomb. 2011; 28:80-4.
HUTCHINSON M. Cerebrospinal fluid oligoclonal bands are important in the diagnosis of multiple sclerosis, unreasonably downplayed by the McDonald criteria 2010: Commentary. Mult Scler. 2013; 19:717-8.
CHATAWAY J. When confronted by a patient with the radiologically isolated syndrome. Pract Neurol. 2010; 10:271-7.
OKUDA DT, MOWRY EM, BEHESHTIAN A, WAUBANT E, BARANZINI SE, GOODIN DS, et al. Incidental MRI anomalies suggestive of multiple sclerosis: the radiologically isolated syndrome. Neurology. 2009; 72:800-5.
OKUDA DT, MOWRY EM, CREE BA, CRABTREE EC, GOODIN DS, WAUBANT E, et al. Asymptomatic spinal cord lesions predict disease progression in radiologically isolated syndrome. Neurology. 2011; 76:686-92.
LEBRUN C, BENSA C, DEBOUVERIE M, WIERTLEVSKI S, BRASSAT D, DE SEZE J, et al. Association between clinical conversion to multiple sclerosis in radiologically isolated syndrome and magnetic resonance imaging, cerebrospinal fluid, and visual evoked potential: Follow-up of 70 patients. Arch Neurol. 2009; 66: 841-6.
GRANBERG T, MARTOLA J, KRISTOFFERSEN-WIBERG M, ASPELIN P, FREDRIKSON S. Radiologically isolated syndrome--incidental magnetic resonance imaging findings suggestive of multiple sclerosis, a systematic review. Mult Scler. 2013; 19:271-80.
SELLNER J, SCHIRMER L, HEMMER B, MÜHLAU M. The radiologically isolated syndrome: take action when the unexpected is uncovered? J Neurol. 2010;257:1602-11.
SCHWARTZ J, WINTERS JL, PADMANABHAN A, BALOGUN RA, DELANEY M, LINENBERGER ML, et al. Guidelines on the use of therapeutic
apheresis in clinical practice-evidence-based approach from the Writing Committee of the American Society for Apheresis: the sixth special issue. J Clin Apher. 2013; 28:145-284.
LEHMANN HC, HARTUNG HP, HETZEL GR, STÜVE O, KIESEIER BC. Plasma exchange in neuroimmunological
disorders: Part 1: Rationale and treatment of inflammatory central nervous system disorders. Arch Neurol. 2006;63:930-5.
WEINER HL, DAU PC, KHATRI BO, PETAJAN JH, BIRNBAUM G, MCQUILLEN MP, et al. Double- blind study of true vs. sham plasma exchange in patients treated with immunosuppression for acute attacks of multiple sclerosis. Neurology. 1989; 39:1143-9.
CORTESE I, CHAUDHRY V, SO YT, CANTOR F, CORNBLATH DR, RAE-GRANT A. Evidence-based guideline update: Plasmapheresis in neurologic disorders: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology. 2011; 76:294-300.
WEINSHENKER BG, O’BRIEN PC, PETTERSON TM, NOSEWORTHY JH, LUCCHINETTI CF, DODICK DW, et al. A randomized trial of plasma exchange in acute central nervous system inflammatory demyelinating disease. Ann Neurol. 1999; 46:878-86.
MAGAÑA SM, KEEGAN BM, WEINSHENKER BG, ERICKSON BJ, PITTOCK SJ, LENNON VA, et al. Beneficial plasma exchange response in central nervous system inflammatory demyelination. Arch Neurol. 2011; 68:870-8.
THE CANADIAN COOPERATIVE MULTIPLE SCLEROSIS STUDY GROUP. The Canadian cooperative trial of cyclophosphamide and plasma
exchange in progressive multiple sclerosis. Lancet. 1991; 337:441-6.
GORDON PA, CARROLL DJ, ETCHES WS, JEFFREY V, MARSH L, MORRICE BL, et al. A double- blind controlled pilot study of plasma exchange versus sham apheresis in chronic progressive multiple sclerosis. Can J Neurol Sci. 1985; 12:39-44.
SORENSEN PS, WANSCHER B, SZPIRT W, JENSEN CV, RAVNBORG M, CHRISTIANSEN P, et al. Plasma exchange combined with azathioprine in multiple sclerosis using serial gadolinium-enhanced MRI to monitor disease activity: a randomized single- masked cross-over pilot study. Neurology 1996; 46:1620-5.
HELLWIG K, BRUNE N, HAGHIKIA A, MÜLLER T, SCHIMRIGK S, SCHWÖDIAUER V, et al. Reproductive counselling, treatment and course
of pregnancy in 73 German MS patients. Acta Neurol Scand. 2008; 118:24-8.
HENSHAW SK. Unintended pregnancy in the United States. Fam Plann Perspect. 1998; 30:24-9.
WEBER-SCHOENDORFER C, SCHAEFER C. Multiple sclerosis, immunomodulators, and pregnancy outcome: a prospective observational study. Mult Scler. 2009; 15:1037-42.
BOSKOVIC R, WIDE R, WOLPIN J, BAUER DJ, KOREN G. The reproductive effects of beta interferon therapy in pregnancy: a longitudinal cohort. Neurology. 2005; 65:807-11.
LU E, WANG BW, GUIMOND C, SYNNES A, SANDOVNICK D, TREMLETT H. Disease-modifying drugs for multiple sclerosis in pregnancy: a systematic review. Neurology. 2012; 79:1130-5.
PATTI F, CAVALLARO T, LO FERMO S, NICOLETTI A, CIMINO V, VECCHIO R, et al. Is in utero early-exposure to interferon beta a risk factor for pregnancy outcomes in multiple sclerosis? J Neurol. 2008; 255:1250-3.
BOOTHBY LA, DOERING PL. FDA labeling system for drugs in pregnancy. Ann Pharmacother. 2001; 35:1485-9.
KUPERSMITH MJ, KAUFMAN D, PATY DW, EBERS G, MCFARLAND H, JOHNSON K, ET AL. Megadose corticosteroids in multiple sclerosis. Neurology. 1994; 44:1-4.
MURRAY TJ. Diagnosis and treatment of multiple sclerosis. BMJ. 2006; 332:525-7.
DURELLI L, COCITO D, RICCIO A, BARILE C, BERGAMASCO B, BAGGIO GF, et al. High-dose intravenous methylprednisolone in the treatment of multiple sclerosis: clinical-immunologic correlations. Neurology. 1986; 36:238-43.
FILIPPINI G, BRUSAFERRI F, SIBLEY WA, CITTERIO A, CIUCCI G, MIDGARD R, et al. Corticosteroids or ACTH for acute exacerbations in multiple sclerosis. Cochrane Database Syst Rev. 2000; (4):CD001331.
MILLIGAN NM, NEWCOMBE R, COMPSTON DA. A double-blind controlled trial of high dose methylprednisolone in patients with multiple sclerosis: 1. Clinical effects. J Neurol Neurosurg Psychiatry. 1987; 50:511-6.
BARNES D, HUGHES RA, MORRIS RW, WADE-JONES O, BROWN P, BRITTON T, et al. Randomised trial of oral and intravenous methylprednisolone in acute relapses of multiple sclerosis. Lancet. 1997; 349:902-6.
NATIONAL INSTITUTE FOR CLINICAL EXCELLENCE. Management of multiple sclerosis in primary and secondary care. NICE Clinical Guidelines, No. 8. 2003 [Actualizado 2010 Mar 30; Citado 2013 Sep 20]. Disponible en: http://www.nice.org.
uk/nicemedia/live/10930/29199/29199.pdf
ASCHERIO A, MUNGER KL, SIMON KC. Vitamin D and multiple sclerosis. Lancet Neurol. 2010; 9:599-612.
CARLSON NG, ROSE JW. Vitamin D as a clinical biomarker in multiple sclerosis. Expert Opin Med Diagn. 2013; 7:231-42.
POZUELO-MOYANO B, BENITO-LEÓN J. Vitamin D and multiple sclerosis. Rev Neurol. 2013; 56:243-51.
PIERROT-DESEILLIGNY C. Clinical implications of a possible role of vitamin D in multiple sclerosis. J Neurol. 2009; 256:1468-79.
HOLMØY T, KAMPMAN MT, SMOLDERS J. Vitamin D in multiple sclerosis: implications for assessment and treatment. Expert Rev Neurother. 2012; 12:1101-12.
POZUELO-MOYANO B, BENITO-LEON J, MITCHELL AJ, HERNANDEZ- GALLEGO J. A systematic review of randomized, double-blind, placebo- controlled trials examining the clinical efficacy of vitamin D in multiple sclerosis. Neuroepidemiology. 2012; 40:147-53.
SIMON KC, MUNGER KL, KRAFT P, HUNTER DJ, DE JAGER PL, ASCHERIO A. Genetic predictors of 25-hydroxyvitamin D levels and risk of multiple sclerosis. J Neurol. 2011; 258:1676-82.
STEIN MS, LIU Y, GRAY OM, BAKER JE, KOLBE SC, DITCHFIELD MR, ET AL. A randomized trial of high-dose vitamin D2 in relapsing-remitting multiple sclerosis. Neurology. 2011; 77:1611-8.
DÖRR J, OHLRAUN S, SKARABIS H, PAUL F. Efficacy of vitamin D supplementation in multiple sclerosis (EVIDIMS Trial): study protocol for a randomized controlled trial. Trials. 2012; 13:15.
GIBSON JC, SUMMERS GD. Bone health in multiple sclerosis. Osteoporos Int. 2011;22: 2935-49.
LAMIREL C, NEWMAN NJ, BIOUSSE V. Optical Coherence Tomography (OCT) in Optic Neuritis and Multiple Sclerosis. Rev Neurol (Paris). 2010; 166:978-86.
COSTELLO F. Evaluating the Use of Optical Coherence Tomography in Optic Neuritis. Mult Scler Int. 2011; 2011:148394.
PETZOLD A, DE BOER JF, SCHIPPLING S, VERMERSCH P, KARDON R, GREEN A, et al. Optical coherence tomography in multiple sclerosis: a systematic review and meta-analysis. Lancet Neurol. 2010; 9:921-32.
NAISMITH RT, TUTLAM NT, XU J, KLAWITER EC, SHEPHERD J, TRINKAUS K, et al. Optical coherence tomography differs in neuromyelitis optica compared with multiple sclerosis. Neurology 2009; 72:1077-82.
RATCHFORD JN, QUIGG ME, CONGER A, FROHMAN T, FROHMAN E, BALCER LJ, et al. Optical coherence tomography helps differentiate
neuromyelitis optica and MS optic neuropathies. Neurology. 2009; 73:302-8.
VIDAL-JORDANA Á, SASTRE-GARRIGA J, MONTALBAN X. Optical coherence tomography in multiple sclerosis. Rev Neurol. 2012; 54:556-63.
SEPULCRE J, MURIE-FERNANDEZ M, SALINAS- ALAMAN A, GARCIA-LAYANA A, BEJARANO B, VILLOSLADA P. Diagnostic accuracy of retinal
abnormalities in predicting disease activity in MS. Neurology. 2007; 68:1488-94.
COSTELLO F, HODGE W, PAN YI, EGGENBERGER E, COUPLAND S, KARDON RH. Tracking retinal nerve fiber layer loss after optic neuritis: a prospective study using optical coherence tomography. Mult Scler. 2008; 14:893-905.
KILLESTEIN J, RUDICK RA, POLMAN CH. Oral treatment for multiple sclerosis. Lancet Neurol. 2011; 10:1026-34.
FREEDMAN MS. Present and emerging therapies for multiple sclerosis. Continuum. 2013; 19:968-91.
FOX EJ, RHOADES RW. New treatments and treatment goals for patients with relapsing-remitting multiple sclerosis. Curr Opin Neurol. 2012;25:S11-9.
PELLETIER D, HAFLER DA. Fingolimod for multiple sclerosis. N Engl J Med. 2012; 366:339-47.
FAZEKAS F, BERGER T, FABJAN TH, LEDINEK AH, JAKAB G, KOMOLY S, et al. Fingolimod in the treatment algorithm of relapsing remitting multiple sclerosis: a statement of the Central and East European (CEE) MS Expert Group. Wien Med Wochenschr. 2012; 162:354-66.
HE D, XU Z, DONG S, ZHANG H, ZHOU H, WANG L, et al. Teriflunomide for multiple sclerosis. Cochrane Database Syst Rev. 2012;12:CD009882.
FREEDMAN MS, WOLINSKY JS, WAMIL B, CONFAVREUX C, COMI G, KAPPOS L, et al. Teriflunomide added to interferon-β in relapsing multiple sclerosis: a randomized phase II trial. Neurology. 2012; 78:1877-85.
GOLD R, KAPPOS L, ARNOLD DL, BAR-OR A, GIOVANNONI G, SELMAJ K, et al. Placebo- controlled phase 3 study of oral BG-12 for
relapsing multiple sclerosis. N Engl J Med. 2012; 367:1098-107.
FOX RJ, MILLER DH, PHILLIPS JT, HUTCHINSON M, HAVRDOVA E, KITA M, et al. Placebo-controlled phase 3 study of oral BG-12 or
glatiramer in multiple sclerosis. N Engl J Med. 2012; 367:1087-97.
COMI G, JEFFERY D, KAPPOS L, MONTALBAN X, BOYKO A, ROCCA MA, et al. Placebocontrolled trial of oral laquinimod for multiple sclerosis. N Engl J Med. 2012; 366:1000-9.
COHEN JA, BARKHOF F, COMI G, HARTUNG HP, KHATRI BO, MONTALBAN X, et al. Oral fingolimod or intramuscular interferon
for relapsing multiple sclerosis. N Engl J Med. 2010; 362:402-15.
SINGER BA. Initiating oral fingolimod treatment in patients with multiple sclerosis. Ther Adv Neurol Disord. 2013; 6:269-75.
ONTANEDA D, FOX RJ. Multiple sclerosis treatment: risk mitigation. Continuum. 2013; 19:1092-9.
ROMMER PS, STÜVE O. Management of secondary progressive multiple sclerosis: prophylactic treatment-past, present, and future aspects. Curr Treat Options Neurol. 2013; 15:241-58.
GOODIN DS, FROHMAN EM, GARMANY GP JR, HALPER J, LIKOSKY WH, LUBLIN FD, et al. Disease modifying therapies in multiple sclerosis: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and the MS Council for Clinical Practice Guidelines. Neurology. 2002; 58:169-78.
KAPPOS L, WEINSHENKER B, POZZILLI C, THOMPSON AJ, DAHLKE F, BECKMANN K, et al. Interferon beta-1b in secondary progressive
MS: a combined analysis of the two trials. Neurology. 2004;63:1779-87.
HARTUNG HP, GONSETTE R, KÖNIG N, KWIECINSKI H, GUSEO A, MORRISSEY, et al. Mitoxantrone in progressive multiple sclerosis: a
placebo-controlled, double-blind, randomised, multicentre trial. Lancet. 2002; 360:2018-25.
GOODIN DS, ARNASON BG, COYLE PK, FROHMAN EM, PATY DW. The use of mitoxantrone (Novantrone) for the treatment of multiple
sclerosis: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology. 2003; 61:1332-8.
FERNÁNDEZ O, GUERRERO M, MAYORGA C, MUÑOZ L, LEÁN A, LUQUE G, et al. Combination therapy with interferon ß-1b and azathioprine in secondary progressive Multiple Sclerosis. A twoyear pilot study. J Neurol. 2002; 249:1058-62.
GOODKIN DE, KINKEL RP, WEINSTOCKGUTTMAN B, VANDERBRUG-MEDENDORP S, SECIC M, GOGOL D, et al. A phase II study of i.v.
methylprednisolone in secondary-progressive multiple sclerosis. Neurology. 1998; 51:239-45.
HAUSER SL, DAWSON DM, LEHRICH JR, BEAL MF, KEVY SV, PROPPER RD, et al. Intensive Immunosuppression in Progressive Multiple Sclerosis — A Randomized, Three-Arm Study of High-Dose Intravenous Cyclophosphamide, Plasma Exchange, and ACTH. N Engl J Med. 1983; 308:173-80.
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