Clinical characterization of long-term multiple sclerosis (COLuMbus) patients in Argentina: A cross-sectional non-interventional study.

BACKGROUND: Most Multiple Sclerosis (MS) clinical trials fail to assess the long-term effects of disease-modifying therapies (DMT) or disability. METHODS: COLuMbus was a single-visit, cross-sectional study in Argentina in adult patients with ≥10 years of MS since first diagnosis. The primary endpoint was to determine patient disability using the Expanded Disability Status Scale (EDSS). The secondary endpoints were to evaluate the distribution of diagnoses between relapsing-remitting MS (RRMS) and secondary progressive MS (SPMS), patient demographics, disease history, and the risk of disability progression. The relationship between baseline characteristics and the current disability state and the risk of disability progression was assessed. RESULTS: Out of the 210 patients included, 76.7 % had a diagnosis of RRMS and 23.3 % had been diagnosed with SPMS, with a mean disease duration of 17.9 years and 20.5 years, respectively. The mean delay in the initial MS diagnosis was 2.6 years for the RRMS subgroup and 2.8 years for the SPMS subgroups. At the time of cut-off (28May2020), 90.1 % (RRMS) and 75.5 % (SPMS) of patients were receiving a DMT, with a mean of 1.5 and 2.0 prior DMTs, respectively. The median EDSS scores were 2.5 (RRMS) and 6.5 (SPMS). In the RRMS and SPMS subgroups, 23 % and 95.9 % of patients were at high risk of disability, respectively; the time since first diagnosis showed a significant correlation with the degree of disability. CONCLUSIONS: This is the first local real-world study in patients with long-term MS that highlights the importance of recognizing early disease progression to treat the disease on time and delay disability.

Siponimod (BAF312): Características generales e implicancias clínicas de la dosificación farmacogenómica en el tratamiento de la Esclerosis Múltiple secundaria progresiva / Siponimod (BAF312): General Characteristics and Clinical Implications of Pharmacogenomic Dosage in the Treatment of Active Secondary Progressive Multiple Sclerosis

Siponimod es un medicamento inmunosupresor selectivo, desarrollado como la primera terapia oral para la esclerosis múltiple secundaria progresiva activa. Este medicamento actúa modulando el receptor de esfingosina 1 fosfato (S1P), como antagonista de S1P1 y S1P5, evitando así la salida de linfocitos desde los nódulos linfáticos y previniendo procesos inflamatorios en el Sistema Nervioso Central que desencadenan una desmielinización. Existe amplio conocimiento científico respecto a que la administración del medicamento a pacientes va a depender de sus características farmacogenéticas, por lo que la FDA recomienda fuertemente realizar un estudio de genotipificación de la enzima que metaboliza siponimod, CYP2C9, cuyas variantes genéticas *2 y *3 clasifican a pacientes como metabolizadores pobres, extensivos o rápidos. Para pacientes homocigotos de CYP2C9*3 siponimod está totalmente contraindicado. Adicionalmente, antes de su prescripción se debe realizar un electrocardiograma, evaluaciones del estado de anticuerpos, oftálmica, estado de vacunación contra varicela y recuento de linfocitos periféricos, ya que el efecto del medicamento es dependiente de la dosis administrada, por lo que se realiza un proceso de titulación en dosis desde los 0,25mg hasta los 2 mg. El protocolo farmacoterapéutico de siponimod es reflejo fidedigno de la utilidad de la farmacogenética en la medicina personalizada..

Siponimod is a selective immunosuppressive medication, developed as the first oral therapy for active secondary progressive multiple sclerosis. This medication acts by modulating the sphingosine 1 phosphate (S1P) receptor, as an antagonist of S1P1 and S1P5, thus preventing the egress of lymphocytes from lymph nodes and preventing inflammatory processes in the Central Nervous System that trigger demyelination. There is extensive scientific knowledge regarding the administration of the medication to patients, which will depend on their pharmacogenetic characteristics. Therefore, the FDA strongly recommends conducting a genotyping study of the enzyme that metabolizes siponimod, CYP2C9, whose genetic variants *2 and *3 classify patients as poor, extensive, or rapid metabolizers. Siponimod is completely contraindicated for patients who are homozygous for CYP2C9*3. Additionally, before prescribing it, an electrocardiogram, assessments of antibody status, ophthalmic evaluation, varicella vaccination status, and peripheral lymphocyte count should be conducted, as the medication's effect is dose-dependent. Therefore, a titration process is carried out starting from 0.25mg up to 2 mg. The pharmacotherapeutic protocol of siponimod is a reliable reflection of the utility of pharmacogenetics in personalized medicine.

[Siponimod (BAF312): General Characteristics and Clinical Implications of Pharmacogenomic Dosage in the Treatment of Active Secondary Progressive Multiple Sclerosis]. / Siponimod (BAF312): Características generales e implicancias clínicas de la dosificación farmacogenómica en el tratamiento de la Esclerosis Múltiple secundaria progresiva.

Siponimod is a selective immunosuppressive medication, developed as the first oral therapy for active secondary progressive multiple sclerosis. This medication acts by modulating the sphingosine 1 phosphate (S1P) receptor, as an antagonist of S1P1 and S1P5, thus preventing the egress of lymphocytes from lymph nodes and preventing inflammatory processes in the Central Nervous System that trigger demyelination. There is extensive scientific knowledge regarding the administration of the medication to patients, which will depend on their pharmacogenetic characteristics. Therefore, the FDA strongly recommends conducting a genotyping study of the enzyme that metabolizes siponimod, CYP2C9, whose genetic variants *2 and *3 classify patients as poor, extensive, or rapid metabolizers. Siponimod is completely contraindicated for patients who are homozygous for CYP2C9*3. Additionally, before prescribing it, an electrocardiogram, assessments of antibody status, ophthalmic evaluation, varicella vaccination status, and peripheral lymphocyte count should be conducted, as the medication's effect is dose-dependent. Therefore, a titration process is carried out starting from 0.25mg up to 2 mg. The pharmacotherapeutic protocol of siponimod is a reliable reflection of the utility of pharmacogenetics in personalized medicine.

Is there a role for off-label high-efficacy disease-modifying drugs in progressive multiple sclerosis? A network meta-analysis.

Ocrelizumab and siponimod are the two on-label drugs used for progressive forms of multiple sclerosis (PMS). However, many patients with PMS do not have access to these high-efficacy disease-modifying drugs (DMDs). Off-label prescription of other high-efficacy DMDs (fingolimod, rituximab and natalizumab) may be a strategy to improve access to immunotherapy for these patients. We aim to compare on-label and off-label high-efficacy drugs for their effect on disability progression in PMS. In December 2021, we searched MEDLINE (PubMed), Embase, Cochrane Central and Scopus databases for randomized clinical trials involving patients with PMS. High-efficacy drugs were considered as intervention and placebos as comparison. The outcome contemplated was risk of Expanded Disability Severity Scale (EDSS) progression at 2 years. A network meta-analysis was performed to compare the relative risk of EDSS progression at 2 years compared with placebo in on-label and off-label drugs. We included five studies with 4526 patients. The median EDSS progression at 2 years in patients that received any immunotherapy was 30%, compared with 35% in placebo groups. Overall, the risk of bias of individual studies was low. Network analysis revealed overlapping confidence intervals in off-label drugs (CI95% 0.51-2.16) versus ocrelizumab (reference) and off-label drugs (CI 95% 0.53-1.96) versus siponimod (reference), suggesting similar efficacy. The same result was found even after excluding studies with the risk of publication bias. Off-label high efficacy immunotherapy in PMS has biological plausibility and presented similar effectiveness to on-label DMDs in this network meta-analysis. The use of fingolimod, rituximab or natalizumab may be a strategy that reduces costs and improves access to immunotherapy for patients with PMS.

Ofatumumabe em primeira linha de terapia modificadora do curso da doença para o tratamento da esclerose múltipla recorrente / First-line ofatumumab therapy disease course modifier for the treatment of recurrent multiple sclerosis

INTRODUÇÃO: A Esclerose Múltipla (EM) é uma doença imunogênica, inflamatória, desmielinizante e neurodegenerativa que acomete a substância branca e a cinzenta do sistema nervoso central (SNC). O quadro clínico se manifesta, na maior parte das vezes, por surtos ou ataques agudos, podendo entrar em remissão de forma espontânea ou com o uso de medicamentos. Denomina-se esclerose múltipla recorrente (EMR) o agrupamento das formas clínicas ativas esclerose múltipla remitente recorrente (EMRR); esclerose múltipla secundária progressiva (EMSP) e síndrome clinicamente isolada (Clinically Isolated Syndrome - CIS), com presença de recorrências ou sinais radiológicos de atividade de doença, ou seja, as formas que são caracterizadas pela ocorrência de surtos inflamatórios. O tratamento da EM pode ser complexo, com o uso de condutas medicamentosas e não medicamentosas. O objetivo do tratamento medicamentoso é a melhora clínica, o aumento da capacidade funcional, a redução de comorbidades e a atenuação de sintomas. As terapias modificadoras do curso da doença (TMCD) visam a reduzir as células imunogênicas circulantes, suprimir a adesão destas ao epitélio e, consequentemente, reduzir a sua migração para o parênquima e a resposta inflamatória decorrente. As seguint

Alentuzumabe para tratamento de pacientes com esclerose múltipla remitente recorrente com características comparáveis aos critérios de tratamento com natalizumabe conforme o estabelecido no PCDT / Alentuzumab for the treatment of patients with relapsing-remitting multiple sclerosis with characteristics comparable to the treatment criteria with natalizumab as per the established in the PCDT

INTRODUÇÃO: A esclerose múltipla (EM) pode ser definida como uma doença crônica, inflamatória, desmielinizante, neurodegenerativa e complexa, sendo caracterizada pela presença de episódios de disfunção neurológica em áreas do sistema nervoso central (cérebro, medula espinhal e nervos ópticos) separados no tempo e no espaço. A EM geralmente afeta adultos jovens, dos 20 aos 50 anos de idade, embora alguns indivíduos possam experimentar o evento desmielinizante durante a infância ou adolescência. A EM pode ser dividida em quatro variações fenotípicas: a EMRR, a EM Secundária Progressiva, a EM Primária Progressiva e a Síndrome Clinicamente Isolada. Atualmente, o Protocolo Clínico e Diretrizes Terapêuticas (PCTD) de EM conta com nove medicamentos classificados como terapias modificadoras do curso da doença (betainterferona 1a intramuscular, betainterferona 1a subcutânea, betainterferona 1b subcutânea, glatirâmer, teriflunomida, fumarato de dimetila, azatioprina, fingolimode, natalizumabe) e um para o tratamento dos surtos (metilprednisolona). O objetivo do presente relatório é analisar as evidências científicas sobre o uso do alentuzumabe para o tratamento de pacientes com EMRR a

Aspectos clínicos y demográficos de los pacientes con esclerosis múltiple secundaria progresiva en Argentina / Clinical and demographic aspects of secondary progressive multiple sclerosis in Argentina

Resumen El objetivo del estudio fue evaluar los aspectos clínicos y demográficos de los pacientes con esclerosis múltiple (EM) secundaria progresiva (EMSP) en los pacientes incluidos en el Registro Argentino de EM (RelevarEM, número de registro de Clinical Trials 03375177). RelevarEM es un registro longitudinal, estrictamente observacional, de pacientes con EM y trastornos del espectro de neuromielitis óptica. Los aspectos clínicos y demográficos fueron descriptos en pacientes con EMSP respecto a aquellos con EM recaída en remisión (EMRR). Se incluyeron 1723 pacientes con EM (1605, 93.2% EMRR y 118, 6.8%, EMSP). En el grupo con EMSP la mediana de edad fue de 53 (intervalo inter-cuartil [IIQ] 47-62) años, 67% eran mujeres, mediana de tiempo de evolución de enfermedad 19.5 (IIQ 14-26) años, EDSS (expanded disability status scale), 6.5 y 48.3% estaban en tratamiento para su EM. Solo el 23.7% con EMSP estaban trabajando activamente y el 86% tenía certificado de discapacidad. Un 35.6% con EMSP presentaron nuevas lesiones en resonancia magnética y 5% tuvo recaídas clínicas en los 12 meses previos al análisis, mostrando una actividad de la enfermedad significativamente menor respecto a la forma EMRR (p < 0.01).

Abstract The objective of the study was to describe the clinical and demographic aspects of patients with secondary progressive multiple sclerosis (SPMS) included in the Argentine MS Registry (RelevarEM, Clinical Trials registry number 03375177). RelevarEM is a longitudinal, strictly observational registry of patients with MS and neuromyelitis optica spectrum disorders. Clinical and demographic aspects were described in patients with SPMS and compared with relapsing remitting MS patients (RRMS). A total of 1723 patients with MS were included (1605, 93.2% RRMS and 118, 6.8%, SPMS). In SPMS, the median age was 53 (inter quartile range [IQR] 47-62) years, 67% were women, median disease duration of 19.5 (IQR 14-26) years, median EDSS (expanded disability status scale) 6.5 and 48.3% were under treatment for their MS. Only 23.7% of patients with SPMS were actively working and 86% had a disability certificate; 35.6% of patients with SPMS presented new lesions in MRI and 5% had clinical relapses during the past 12 months of the registry entry showing a significantly lower disease activity compared with RRMS (p < 0.01).

[Clinical and demographic aspects of secondary progressive multiple sclerosis in Argentina]. / Aspectos clínicos y demográficos de los pacientes con esclerosis múltiple secundaria progresiva en Argentina.

The objective of the study was to describe the clinical and demographic aspects of patients with secondary progressive multiple sclerosis (SPMS) included in the Argentine MS Registry (RelevarEM, Clinical Trials registry number 03375177). RelevarEM is a longitudinal, strictly observational registry of patients with MS and neuromyelitis optica spectrum disorders. Clinical and demographic aspects were described in patients with SPMS and compared with relapsing remitting MS patients (RRMS). A total of 1723 patients with MS were included (1605, 93.2% RRMS and 118, 6.8%, SPMS). In SPMS, the median age was 53 (inter quartile range [IQR] 47-62) years, 67% were women, median disease duration of 19.5 (IQR 14-26) years, median EDSS (expanded disability status scale) 6.5 and 48.3% were under treatment for their MS. Only 23.7% of patients with SPMS were actively working and 86% had a disability certificate; 35.6% of patients with SPMS presented new lesions in MRI and 5% had clinical relapses during the past 12 months of the registry entry showing a significantly lower disease activity compared with RRMS (p < 0.01).

El objetivo del estudio fue evaluar los aspectos clínicos y demográficos de los pacientes con esclerosis múltiple (EM) secundaria progresiva (EMSP) en los pacientes incluidos en el Registro Argentino de EM (RelevarEM, número de registro de Clinical Trials 03375177). RelevarEM es un registro longitudinal, estrictamente observacional, de pacientes con EM y trastornos del espectro de neuromielitis óptica. Los aspectos clínicos y demográficos fueron descriptos en pacientes con EMSP respecto a aquellos con EM recaída en remisión (EMRR). Se incluyeron 1723 pacientes con EM (1605, 93.2% EMRR y 118, 6.8%, EMSP). En el grupo con EMSP la mediana de edad fue de 53 (intervalo inter-cuartil [IIQ] 47-62) años, 67% eran mujeres, mediana de tiempo de evolución de enfermedad 19.5 (IIQ 14-26) años, EDSS (expanded disability status scale), 6.5 y 48.3% estaban en tratamiento para su EM. Solo el 23.7% con EMSP estaban trabajando activamente y el 86% tenía certificado de discapacidad. Un 35.6% con EMSP presentaron nuevas lesiones en resonancia magnética y 5% tuvo recaídas clínicas en los 12 meses previos al análisis, mostrando una actividad de la enfermedad significativamente menor respecto a la forma EMRR (p < 0.01).

Efficacy of andrographolide in not active progressive multiple sclerosis: a prospective exploratory double-blind, parallel-group, randomized, placebo-controlled trial.

BACKGROUND: Multiple sclerosis (MS) is a chronic immune mediated disease and the progressive phase appears to have significant neurodegenerative mechanisms. The classification of the course of progressive MS (PMS) has been re-organized into categories of active vs. not active inflammatory disease and the presence vs. absence of gradual disease progression. Clinical trial experience to date in PMS with anti-inflammatory medications has shown limited effect. Andrographolide is a new class of anti-inflammatory agent, that has been proposed as a potential drug for autoimmune disorders, including MS. In the present trial, we perform an exploratory pilot study on the efficacy and safety of andrographolide (AP) compared to placebo in not active PMS. METHODS: A pilot clinical trial using 140 mg oral AP or placebo twice daily for 24 months in patients with not active primary or secondary progressive MS was conducted. The primary efficacy endpoint was the mean percentage brain volume change (mPBVC). Secondary efficacy endpoints included 3-month confirmed disability progression (3-CDP) and mean EDSS change. RESULTS: Forty-four patients were randomized: 23 were assigned to the AP group, and 21 were assigned to the placebo group. The median baseline EDSS of both groups was 6.0. Annualized mPBVC was - 0.679% for the AP group and - 1.069% for the placebo group (mean difference: -0.39; 95% CI [- 0.836-0.055], p = 0.08, relative reduction: 36.5%). In the AP group, 30% had 3-CDP compared to 41% in the placebo group (HR: 0.596; 95% CI [0.200-1.777], p = 0.06). The mean EDSS change was - 0.025 in the AP group and + 0.352 in the placebo group (mean difference: 0.63, p = 0.042). Adverse events related to AP were mild rash and dysgeusia. CONCLUSIONS: AP was well tolerated and showed a potential effect in reducing brain atrophy and disability progression, that need to be further evaluated in a larger clinical trial. TRIAL REGISTRATION: ClinicalTrials.gov NCT02273635 retrospectively registered on October 24th, 2014.

Efectividad y seguridad del interferón ß1a recombinante, interferón ß1b, acetato de glatiramer, natalizumab y fingolimod para la prevención de la progresión de la discapacidad en pacientes adultos con diagnóstico de esclerosis múltiple de tipo recaída-remisión o secundaria progresiva / Effectiveness and safety of recombinant interferon ß1a, interferon ß1b, glatiramer acetate, natalizumab and fingolimod for the prevention of the progression of disability in adult patients with relapsed-type multiple sclerosis

En Colombia se han aprobado cinco medicamentos para el uso en EM: interferón 1a y 1b, acetato de glatiramer, natalizumab y fingolimod. Todos ellos han demostrado que reducen el número de recaídas y el número de lesiones nuevas en la resonancia magnética cerebral [4]. La importancia del tratamiento a largo plazo de la esclerosis múltiple con medicamentos modificadores del curso de la enfermedad (interferones y acetato de glatiramer) ha sido previamente demostrada [5]. Esta importancia se debe a que varios ensayos clínicos han presentado, en análisis exploratorios, que la terapia con estos fármacos a largo plazo retrasan el tiempo de aparición de una progresión significativa de la enfermedad [5]. El uso a largo plazo de natalizumab y fingolimod no ha sido evaluado ya que son medicamentos recientes. En general, los expertos recomiendan el uso de interferones y de acetato de glatiramer como agentes de primera línea y natalizumab y fingolimod como de segunda [4, 8]. Efectividad: el interferón ß1a, a una dosis de 30 mcgs, no tuvo diferencias estadísticamente significativas frente a placebo, mientras que el interferón ß1a, a una dosis de 44 mcgs, disminuye los pacientes con recaídas a los 12 meses (OR 0.59 IC 95% 0.43-0.81), a los 24 meses (OR 0.45 IC 95% 0.28-0.71) y con progresión de la enfermedad a 24 meses (OR 0.65 IC 95% 0.45-0.93). El interferón ß1b disminuye los pacientes con recaídas a los 24 meses (OR 0.55 IC 95% 0.31-0.99). El acetato de glatiramer reduce el número de pacientes con recaídas a los doce meses con un OR de 0.59 95% IC (0.37-0.93). A los 12 y a los 24 meses, el natalizumab disminuye de manera importante los pacientes con recaídas a los con un OR de 0.38 95% IC (0.28-0.51) y 0.32 95% IC (0.24-0.43). Asimismo, disminuye los pacientes que tienen progresión de la enfermedad a los 24 meses, OR 0.56 95% IC (0.42-0.74). Fingolimod aumenta los pacientes que están libres de recaídas con un OR de 2.85 95% IC (2.15-3.78) y aumenta también los pacientes sin progresión de la enfermedad OR 1.49 95% IC (1.06-2.08). La calidad de la evidencia fue alta para tres de los cuatro estudios incluidos, y baja, para el estudio faltante. Seguridad: en general, los interferones, acetato de glatiramer y natalizumab tienen un perfil de seguridad parecido al placebo ya que no hubo diferencias estadísticamente significativas. Sin embargo, los pacientes bajo tratamiento con estos medicamentos tuvieron más riesgo de descontinuar el tratamiento. Los pacientes con natalizumab tienen más riesgo de reacciones de hipersensibilidad RR 25.42 IC 95 (1.55-416) y de reacciones de infusión RR 1.34 IC 95% (1.01-7.12), que son infrecuentes.

Vitamin D-mediated immune regulation in multiple sclerosis.

Although Vitamin D is best known as a modulator of calcium homeostasis, it also has immune modulating potential. A protective effect of Vitamin D on Multiple Sclerosis (MS) is supported by the reduced risk associated with sun exposure and use of Vitamin D supplements. Moreover, high circulating levels of Vitamin D have been associated with lower risk of MS. To gain more insight into putative regulatory mechanisms of Vitamin D in MS pathogenesis, we studied 132 Hispanic patients with clinically definite MS, 58 with relapsing remitting MS (RR MS) during remission, 34 RR MS patients during relapse, and 40 primary progressive MS cases (PP MS). Sixty healthy individuals matched with respect to place of residence, race/ethnicity, age and gender served as controls. Levels of 25(OH) Vitamin D and 1,25(OH)(2) Vitamin D, measured by ELISA were significantly lower in RR MS patients than in controls. In addition, levels in patients suffering relapses were lower than during remissions. By contrast, PP MS patients showed similar values to controls. Proliferation of both freshly isolated CD4+ T cells and MBP-specific T cells was significantly inhibited by 1,25(OH)(2) Vitamin D. Moreover, activated Vitamin D enhanced the development of IL-10 producing cells, and reduced the number of IL-6 and IL-17 secreting cells. Notably, VDR expression was induced by 1,25(OH)(2) Vitamin D in both activated and resting cells. Interestingly, T cells were able to metabolize 25(OH) Vitamin D into biologically active 1,25(OH)(2) Vitamin D, since T cells express 1α-hydroxylase constitutively. Finally, 1,25(OH)(2) Vitamin D also increased the expression and biological activity of IDO, triggering significant increase in the number of CD4+CD25+ T regulatory cells. Collectively, these findings suggest that 1,25(OH)(2) VitaminD plays an important role in T cell homeostasis during the course of MS, suggesting correction of its deficiency may be useful during treatment of the disease.

Benefit with methylprednisolone in continuous pulsetherapy in progressive primary form of multiple sclerosis: study of 11 cases in 11 years.

Primary progressive multiple sclerosis (PPMS) is defined clinically with a progressive course from onset. There is no approved treatment for the PPMS. Methylprednisolone IV (MP) hastens the recovery from MS relapses. We studied 11 patients that met the MacDonald's diagnostic criteria for PPMS. The dose of MP was 30 mg/kg in 250 mL of glucose solution in three consecutive days during the first week, two doses during the second and one dose in the third week. One weekly session for eight consecutive weeks was given. After, a once-a week/eight-week interval was maintained. The medium EDSS before treatment was 6.2, and after 11.2 years of treatment, the EDSS was 4.9. Although we studied a small sample of PPMS we may conclude that therapy with IVMP prevents clinical worsening of MS in the majority of patients with improvement in EDSS scores.

Benefit with methylprednisolone in continuous pulsetherapy in progressive primary form of multiple sclerosis: study of 11 cases in 11 years / Benefício do uso de pulsoterapia contínua com metilprednisolona na forma primária progressiva da esclerose múltipla: estudo de 11 casos em 11 anos

Primary progressive multiple sclerosis (PPMS) is defined clinically with a progressive course from onset. There is no approved treatment for the PPMS. Methylprednisolone IV (MP) hastens the recovery from MS relapses. We studied 11 patients that met the MacDonald's diagnostic criteria for PPMS. The dose of MP was 30 mg/kg in 250 mL of glucose solution in three consecutive days during the first week, two doses during the second and one dose in the third week. One weekly session for eight consecutive weeks was given. After, a once-a week/eight-week interval was maintained. The medium EDSS before treatment was 6.2, and after 11.2 years of treatment, the EDSS was 4.9. Although we studied a small sample of PPMS we may conclude that therapy with IVMP prevents clinical worsening of MS in the majority of patients with improvement in EDSS scores.

A forma progressiva da esclerose múltipla (FPEM) é definida como progressiva desde o início. Não há tratamento eficaz para esta forma. A metilprednisolona por via endovenosa (MPEV) é usada para os surtos de exacerbação da EM. Estudamos 11 pacientes que preenchiam os critérios de MacDonald para FPMS. A dose inicial de MPEV foi de 30 mg/kg em 250 mL de soro glicosado por três dias consecutivos na primeira semana, duas doses na segunda e uma dose na terceira semana. Seguiu-se uma sessão semanal por oito semanas. Após manteve-se uma dose semanal a cada oito semanas. A média do EDDS foi 9,6 antes e 4,9 após 11,2 anos de tratamento. Embora tenhamos estudado número reduzido de casos, podemos dizer que o uso de MPEV impede a progressão da FPEM na maioria dos pacientes estudados com melhora do EDDS.

Clinical course of progressive multiple sclerosis in Brazilian patients.

OBJECTIVE: To describe the clinical course and outcome of multiple sclerosis with progressive onset in Brazilian patients. A total of 238 medical records were reviewed, 26 cases (10.9%) fulfilled Thompson criteria (2000), and 5.80% classified as primary progressive and 5.04% relapsing progressive according to Lublin and Reingold. STUDY POPULATION: 19 Caucasians and 7 non-Caucasians; male:female ratio 1.2:1, mean age at onset was 34 +/- 7.9 years. RESULTS: Non-Caucasian patients had earlier onset of disease. The most common manifestations at onset were pyramidal and cerebellar (89% and 34.6%). After 11.3 +/- 6.35 years of disease more than 50% of the patients had involvement of most of their functional systems. No statistically significant differences were observed between the subgroups. CONCLUSION: The clinical course and outcome of progressive multiple sclerosis in Brazil, a tropical country with low prevalence, were very similar to those in the multiple sclerosis high prevalence areas.

Mitoxantrone in secondarily progressive multiple sclerosis: a series of 18 patients.

Mitoxantrone hydrochloride (Novantrone) is an anthracenedione that has been used as one of the latest in a long line of general immunosuppresive agents studied in multiple sclerosis (MS). We reviewed the clinical, laboratory, neuroimaging and echocardiography data of 18 patients from February 2001 to March 2004 out of a total number of 100 patients with definite MS. Fourteen patients were women (77.7%) and four were men. The mean age of the patients was 41.6 +/- 10 years old (confidence intervals 95%: 36.4-46.7 years old). The mean duration of disease was 10.5 +/- 6.3 years. Fourteen patients had the secondarily progressive form of MS, and four had the relapsing-remitting form. Mitoxantrone is an useful and clinically effective drug in MS and its major limitation is the potencial cardiotoxicity due to cumulative dose (140 mg).

Mitoxantrone in secondarily progressive multiple sclerosis: a series of 18 patients

Hidrocloridrato de mitoxantrone (Novantrone®) é um antracenedione utilizado como o agente mais recente de uma longa linha de imunossupressivos gerais estudados em esclerose múltipla (EM). Realizamos revisão de dados clínicos, laboratoriais, de neuroimagem e ecocardiografia de 18 pacientes, no período de fevereiro de 2001 a março de 2004, a partir de um total de 100 pacientes com EM definida. Quatorze pacientes eram do sexo feminino (77,7%) e quatro eram do sexo masculino. A idade média dos pacientes foi 41,6±10 anos (intervalo de confiança 95%: 36,4-46,7 anos). A duração média da doença foi 10,5±6,3 anos. Quatorze pacientes apresentavam a forma secundária progressiva de EM e quatro a forma surto-remissão. O mitoxantrone é uma droga útil e clinicamente eficaz , sendo a principal limitação sua potencial cardiotoxicidade devido à dose cumulativa (140 mg).

Intravenous immunoglobulin and mitoxantrone stop the progression of secondary progressive multiple sclerosis in a patient with interferon intolerance.

A 36 year-old female patient with secondary progressive multiple sclerosis accompanied by neuropsychiatric depression and history of intolerance to beta-interferon was treated with mitoxantrone (MX) and intravenous immunoglobulin (IVIG) for 2 years. Both clinical response and magnetic resonance imaging were performed at the end. With a combination of MX and IVIG long-term treatment, her disabilities improved as measured by the Expanded Disability Status Scale (EDSS). The combination therapy was well-tolerated. It represents an alternative to treat patients who do not respond well to cytostatics alone, or in those in whom intolerance to interferons may also occur. Immunomodulation with intravenous immunoglobulin stopped the progression of the disease and avoided subsequent exacerbations during 24 months. The role of high doses of immunoglobulins in the treatment of patients with secondary progressive MS deserves clinical trials to evaluate the stopping of progression of the disease in comparison to remissions induced by cytostatics, interferons and steroids.