Esclerosis múltiple: reacciones adversas a medicamentos en pacientes bajo ley 20850, Hospital Regional de Talca / Multiple sclerosis: adverse drug reactions in patients under law 20850, Hospital Regional de Talca

INTRODUCTION: Multiple sclerosis (MS) is a demyelinating disease of the central nervous system, which occurs in up to 85% of cases as relapsing remitting (RR), with episodes of neurological dysfunction partially forwarded. Its treatment in Chile is financially protected by the Explicit Health Guarantees (GES) and Law 20,850 on high-cost diseases. The Regional Hospital of Talca (HRT) has 25 patients benefiting from Law 20,850 in treatment with second-line biologic therapy. Adverse reactions (RAM) to the use of these drugs have been described and to date there are no case reports or studies of significant adverse events in Chile. Objectives: To present the experience of the use of biologic therapy in EMRR in HRT, in relation to adverse events. METHODS: A review of the current guidelines in Chile for the treatment of relapsing-remitting multiple sclerosis and the protocol of law 20,850 was carried out, the clinical records of 25 patients benefiting from the law in the HRT were reviewed, with emphasis on the adverse events presented before First and second line therapies and the con sequences of these events on the continuity of therapy. RESULTS: Half of the patients who started their treatment with first-line drugs had adverse effects, of which 28% involved a change in therapy, the remaining changed from therapy due to failure to treatment. Of the 26 patients included in the sample, 24 are currently using second-line drugs. The profile of adverse effects should be a variable to consider when indicating a therapy for MS.

Fingolimode para o tratamento da esclerose múltipla (2014) / Fingolimode para o tratamento da esclerose múltipla (2014)

CONTEXTO: A Esclerose Múltipla (EM) é uma doença autoimune, desmielinizante, crônica do sistema nervoso central, comum em adultos jovens, predominante entre mulheres, com evolução progressiva e imprevisível. A incidência mundial é de 2,5 casos novos a cada 100.000 pessoas por ano e no Brasil sua taxa de prevalência média é de aproximadamente 15 casos/100.000 habitantes, variando entre as regiões e sendo mais prevalente nas regiões sul e sudeste. Atualmente, segundo PCDT vigente (Portaria SAS/MS nº 493, de 23 de setembro de 2010), acetato de glatirâmer e betainterferona (1A ou 1B) são os fármacos de primeira escolha para o tratamento de Esclerose Múltipla Remitente Recorrente (EMRR). O uso de natalizumabe ocorre em casos refratários, tanto às betainterferonas quanto a glatirâmer. Atualmente, existem 11.650 pacientes recebendo betainterferonas, acetato de glatirâmer e natalizumabe para o tratamento de EM (DATASUS). TRATAMENTO: O tratamento é preconizado apenas para as formas EM-RR e EM-SP, pois não há evidência de benefício para as demais. O Protocolo Clínico e Diretrizes Terapêuticas da Esclerose Múltipla do Ministério da Saúde publicado em novembro de 2013 preconiza as betainterferonas e glatirâmer como primeira escolha e recomenda que o natalizumabe seja iniciado somente em casos refratários tanto a betainterferonas quanto a glatirâmer. A CONITEC já avaliou outras demandas por incorporação do fingolimode ao tratamento de esclerose múltipla no SUS, tendo emitido o relatório número 04, de julho de 2012, no qual não recomendou a incorporação desta tecnologia para a primeira linha de tratamento da esclerose múltipla. O relatório, à época, trouxe como um dos motivos para a não incorporação do medicamento os dados de segurança, que demandava a realização de estudos clínicos de fase IV ou de pós-comercialização a fim de avaliar a segurança do medicamento, especialmente os efeitos adversos cardiovasculares, para que então se reavaliasse a relação risco e benefício da tecnologia. A TECNOLOGIA: Fingolimode é indicado como terapia modificadora de doença para tratamento de pacientes adultos com esclerose múltipla remitente recorrente para reduzir a freqüência de reincidências e retardar a progressão da incapacidade7 (CID G35.0, ou seja, esclerose múltipla). EVIDÊNCIAS CIENTÍFICAS: os demandantes apresentaram em seus pareceres técnico-científicos as buscas realizadas por evidências científicas. Nos três casos, a pergunta de pesquisa foi adequada, considerando os comparadores disponíveis no SUS. Nas três propostas encaminhadas, os demandantes selecionaram o estudo que comparou o fingolimode ao betainterferona-1a (TRANSFORMS) e mais dois artigos que derivaram deste estudo principal, um de extensão do estudo e outro de análise de subgrupo. Os três estudos são de nível de evidência 1B, segundo maior nível de evidência. Os resultados apontam para eficácia superior do fingolimode em relação ao betainterferona-1a, porém ainda há incertezas sobre os resultados de segurança, especialmente para o uso em primeira linha. DELIBERAÇÃO FINAL: Com discussão posterior à Consulta Pública, tendo como base a ausência de dados novos que superassem a incerteza quanto ao balanço de riscos e benefícios do uso do fingolimode em primeira e segunda linha, devido, sobretudo, aos potenciais eventos cardiovasculares relacionados à primeira dose do fingolimode, os membros do plenário, na reunião realizada nos dias 7 e 8/5/2014, deliberaram, por unanimidade, por não recomendar a incorporação do fingolimode para a primeira e segunda linha do tratamento da esclerose múltipla. DECISÕES: PORTARIA Nº 24, de 27 de junho de 2014 - Torna pública a decisão de incorporar o fingolimode no Sistema Único de Saúde nos casos de: pacientes com esclerose múltipla remitente-recorrente; com surtos incapacitantes após falha ao uso de betainterferona e de glatirâmer; com impossibilidade de uso de natalizumabe e sem contraindicação ao uso de fingolimode conforme Protocolo Clínico e Diretrizes Terapêuticas.

Interferon-beta in pediatric multiple sclerosis patients: safety in short-term prescription

None of the approved immunomodulatory drugs in adults Multiple Sclerosis [MS] patients have been officially approved for the pediatric patients and are currently used off-label in this population. In this study, we evaluated the effectiveness and tolerability of intramuscular interferon beta1-a [Avonex[registered]] and subcutaneously injected interferon beta1-b [Betaferon[registered]] in children with definite relapsing-remitting MS [RRMS]. Thirteen patients aged younger than 16, who were recently diagnosed with definite RRMS according to the McDonald's criteria, were enrolled in this study. Six patients were treated with Avonex[registered] 30 micro g, intramuscularly every week, and seven patients were treated with Betaferon[registered] 250 micro g, subcutaneously every other day. All patients were treated with adult doses; initially interferon-beta was prescribed with half dose, and it was increased to full adult dose steadily. Eleven girls and two boys, mean [SD] age of 14.7 [1.9] years, were studied. Following nine months of using interferon-beta, nine patients [69.2%] had no relapses and the remaining four, experienced only one relapse. The mean EDSS score was decreased significantly after the study period. The present study provides reasonable data for the use of interferon-beta in Pediatric MS due to lack of short-term complications and safety. Studies with larger sample size and longer follow up duration are required to shed light on the long term impact of the interferon-beta therapy in children

Literature systematic review on the ophthalmological side effects of interferons / Revisão sistemática da literatura sobre os efeitos adversos oftalmológicos dos interferons

Interferons alpha and beta have been used worldwide for a few decades, altering the natural history of several severe diseases including hepatitis C, cancer and immune-mediated conditions such as multiple sclerosis. The adverse events profile of interferons is well established, but only isolated reports of ophthalmological complications of interferon therapy have been published. The objective of this study was to carry out a literature systematic review on the subject, bringing to light the need for careful ophthalmological monitoring of patients undergoing interferon treatment. Nearly 500 cases of ophthalmological complications related to interferon have been reported. The most frequent findings were soft exudates, hemorrhages and retina ischemia.

Os interferons alfa e beta têm sido usado em todo o mundo por algumas décadas, mudando a história natural de diversas doenças graves, como hepatite C, câncer e condições imunomediadas como a esclerose múltipla. O perfil de eventos adversos dos interferons está bem definido, porém apenas relatos isolados das complicações oftalmológicas do tratamento com interferon foram publicados. O objetivo do presente trabalho foi a realização de uma revisão sistemática da literatura sobre o tema, trazendo à luz a necessidade de cuidadosa monitorização oftalmológica dos pacientes em tratamento com interferon. Quase 500 casos de complicações oftalmológicas relacionadas ao uso de interferon foram relatados. Os achados mais frequentes foram exsudatos, hemorragias e isquemia de retina.

Erupção acneiforme aguda induzida por interferon beta-1b durante tratamento para esclerose múltipla / Acute acneiform eruption induced by interferon beta-1b during treatment for multiple sclerosis

Esclerose múltipla é uma doença inflamatória desmielinizante, com presumida origem autoimune, que afeta o sistema nervoso central. A principal modalidade terapêutica é baseada no uso de imunomoduladores, como o interferon beta, que são geralmente bem tolerados. As manifestações cutâneas secundárias ao interferon beta-1b são representadas, na maioria das vezes, por reações no local de sua aplicação subcutânea. Descrevemos o caso de uma paciente do sexo feminino que desenvolveu um quadro de erupção acneiforme pelo interferon beta-1b.

Multiple sclerosis is an inflammatory demyelinating disease of presumed autoimmune origin that affects the central nervous system. The main form of therapy is based on the use of immunomodulators such as interferon beta, which are usually well tolerated. Skin manifestations resulting from treatment with interferon beta-1b consist principally of reactions at the site of subcutaneous application of the drug. The present case report describes a female patient who developed an acneiform eruption resulting from treatment with interferon beta-1b.

Interferon-beta-1b induced autoimmune hemolytic anemia in a patient with MS: a case report

A 26-year-old lady with the diagnosis of multiple sclerosis who had received interferon beta1-b for eleven months was visited in MS clinic of our hospital because of icter and fatigue. Laboratory tests showed anemia, indirect hyperbillirubinemia, increased LDH, positive direct and indirect coomb's tests, and increased reticulocyte count and percentage. Other causes of autoimmune hemolytic anemia [AHA] and pre-existing AHA in the patient were ruled out. After INF discontinuation, symptoms disappeared, hemoglobin increased, and indirect coomb's test became negative. We concluded that autoimmune hemolytic anemia should be considered in all MS patients who receive interferon beta 1-b and present with symptoms and signs of anemia

Beta interferons in clinically isolated syndromes: a meta-analysis

Beta-interferon use in definite multiple sclerosis (MS) has been proven to modify clinical and magnetic resonance imaging outcome. We review and summarize the data of published double-blind, randomized clinical trials to assess, with a meta-analysis the safety and efficacy of beta-interferon on the occurrence of relapses in patients with a first clinical event suggestive of MS. After two years of follow-up, interferon beta decreased the risk of conversion to clinically definite MS 0.51[0.39-0.65], and delayed the time to diagnosis up to 367 days. Side-effects were mild and self limited. Our findings support the efficacy of early treatment with beta-interferon in reducing conversion to clinically defined MS in patients with clinically isolated syndromes.

Já é suficientemente conhecido que a utilização de interferon beta modifica o prognóstico clínico e de ressonância magnética em pacientes com esclerose múltipla (EM). Revisamos e sumarizamos os dados dos ensaios clínicos, duplo-cegos, randomizados e controlados com placebos para analisar, através de meta-análise, a segurança e eficácia dos interferons-beta sobre a ocorrência de recidivas em pacientes com um primeiro evento clínico sugestivo de EM. Após dois anos de seguimento, os interferons-beta diminuíram o risco de conversão para EM clinicamente definida 0,51[0,39-0,65] e retardaram o tempo para diagnóstico em 367 dias. Os efeitos colaterais foram leves e auto limitados. Nossos dados comprovam a eficácia e segurança do interferon-beta em reduzir a conversão para EM clinicamente definida de pacientes com síndromes clínicas isoladas.

Immunomodulator therapy migration in relapsing remitting multiple sclerosis: a study of 152 cases

BACKGROUND: Since 1997, immunological modulators have been used for treatment of Relapsing Remitting Multiple Sclerosis (RRMS) in the Multiple Sclerosis Attendance and Treatment Center (CATEM) with significant alterations in this disease natural history. AIM: To add data on the experience of CATEM for the treatment of RRMS patients that had immunomodulators. METHOD: RRMS patients that received continuously immunomodulator drugs were evaluated on adherence, migration, withdrawal and progression rates. The patients were divided in three groups by the period of immunomodulators intake. RESULTS: There were registered in Group 1 withdrawal in 98 patients (25 percent) and adherence in 292 cases (74 percent); Group 2 interruption of therapy in 140 patients, 92 (31 percent) due to progression for PSMS, 14 (5 percent) for pregnancy, withdrawal in 34 (11 percent), adherence in 88 percent; Group 3 progression in 41 (26 percent), pregnancy in 3 (2 percent) withdrawal in 42 (27 percent) and adherence in 72 percent. The migration rate was about one third (31.57 percent) and the principal cause was therapeutic failure; the mean migrating time was 0.5-2.5 years in group 3. CONCLUSION: Immunomodulatory treatment for RRMS patients may have significant levels of failure and side effects; the adherence was compatible with the international literature.

INTRODUÇÃO: Na última década foram introduzidos os imunomoduladores para o tratamento da esclerose múltipla (EM) forma remitente-recorrente (RR). OBJETIVO: Complementar o relato anterior da experiência de centro brasileiro no acompanhamento dos pacientes em uso dos imunomoduladores. MÉTODO: 390 pacientes que faziam uso de imunomoduladores no Centro de Atendimento à Esclerose Múltipla (CATEM), foram subdivididos por tempo de uso em três grupos, avaliando-se as ocorrências de: abandono, gravidez, conversão da forma RR para secundária progressiva (SP) e da aderência. RESULTADOS: No Grupo 1, foram observados abandono do uso de imunomoduladores em 98 pacientes (25 por cento) e aderência de 292 casos (74 por cento); no Grupo 2, interrupção da medicação, no total de 140 pacientes, 92 (31 por cento) por conversão para a forma SP, 14 (5 por cento) por gravidez e 34 (11 por cento) por abandono, mantendo a aderência em 88 por cento dos demais pacientes; no Grupo 3, conversão em 41 (26 por cento) dos casos, gravidez em 3 (2 por cento) e abandono em 42 (27 por cento). A aderência se manteve em 72 por cento. O índice de migração foi de quase um terço (31,57 por cento), no grupo 3, tendo como principais causas: a falha terapêutica e efeitos colaterais realizando-se a migração do imunomodulador em 0,5-2,5 anos. CONCLUSÃO: A percentagem de abandono observada é compatível com os dados encontrados na literatura mundial.

Clinical and radiological response and side effects of beta interferon in Iraqi patients with relapsing and remitting multiple sclerosis

To determine the efficacy and tolerability of subcutaneous Interferon beta 1a [IFN beta -1a] among Iraqi patients with relapsing remitting multiple sclerosis [RRMS]. The study was held at the Multiple Sclerosis clinic at Baghdad Teaching Hospital, Baghdad, Iraq from January-October 2004. Thirty-seven patients with clinically definite RRMS and disability status scale below 6.5 were enrolled in this study. Patients received IFN beta -1a, 22 micro g subcutaneously 3 times a week. Clinical measures, including number of relapses and disability progression, with MRI measures including number, size activity of lesions, and brain atrophy were used for evaluation of response to treatment. Side effects were also looked for. Patient ages ranged between 17-60 years with a mean age of 34.85 years, with 20 female patients and 17 male patients. After 2 years of treatment, there was a significant reduction in relapse rate [54.1% were relapse free, and 21.6% had reduction in relapse rate]. There was also a significant effect on disability progression [the mean expanded disability status scale [EDSS] before treatment was 3.22 and mean EDSS after treatment was 2.84]. Significant effects on MRI measures were also shown, presented by a reduction in the number of lesions, which was seen in 64.9% of the patients, and a reduction in the size of lesions, which was seen in 64.9% of the patients. Also, significant effects on the activity of lesions was seen, as 67.6% of the patients had non-active lesions before treatment and remained non-active after treatment, and 29.7% of the patients had active lesions before treatment, which became non-active after 2 years of treatment. Mild adverse reactions were seen, mainly influenza like reactions and injection site reactions. Interferon beta -1a was effective in the treatment of RRMS with minimal side effects

[Evaluation of therapeutic effects of beta IFN on relapsing remitting multiple sclerosis]

There is over 10 years that beta IFN for the treatment of MS is presented to the world of medicine. As there are some doubts about the Pathophysiology of MS, there may be some differences between our patients and other ones; so a study of this type for our own patients is essential. This is a descriptive-analytic and clinical trial study. According to the clinical and paraclinical findings, the patients with the diagnosis of Relapsing Remitting MS included for this study. Severity of disability [according to EDSS and FS] and the numbers of attacks were estimated before and after treatment with IFN/ beta Side effects of IFN beta were evaluated, too. 69% of patients were female and 31% male. Mean age of onset is 26.93 years old and mean duration of disease 5.13 years. Mean relapsing rate before and after of treatment was 1.79 and 0.74 respectively; the difference between these two is significant [P<0.05].The mean of EDSS at the months of O, 3, 6,9,12 was decreased significantly [P0.05]. The most common side effect of IFN-beta in our study is flu like syndrome [27.5%]. Epidemiologic findings of this study such as M/F ratio and age of onset are similar to other studies. Statistical tests revealed the effects of IFN beta on the decrease of disabilities and relapse rate, but there are no differences of these effects between male and female

Fênomeno de Raynaud grave associado a terapia com interferon-beta para esclerose múltipla: relato de caso / Severe Raynaud's phenomenon associated with interferon-beta therapy for multiple sclerosis: case report

Interferon-B (IFN-beta) é usado no tratamento de esclerose múltipla (EM). Descrevemos o caso de uma mulher com EM que apresentou fenômeno de Raynaud grave, livedo reticular e necrose digital duas semanas após tratamento com IFN-beta. Os sintomas melhoraram após suspensão do IFN-beta e início de anticoagulação associada a ciclofosfamida e corticóide. Fenômeno de Raynaud é um efeito colateral provável da terapia com IFN-beta para EM.