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.

Patients' satisfaction with and views about treatment with disease-modifying drugs in multiple sclerosis / Satisfação e pontos de vista dos pacientes com esclerose múltipla em tratamento com drogas modificadoras da doença

ABSTRACT Objective The treatment of multiple sclerosis (MS) with disease-modifying-drugs (DMDs) is evolving and new drugs are reaching the market. Efficacy and safety aspects of the drugs are crucial, but the patients’ satisfaction with the treatment must be taken into consideration. Methods Individual interview with patients with MS regarding their satisfaction and points of view on the treatment with DMDs. Results One hundred and twenty eight patients attending specialized MS Units in five different cities were interviewed. Over 80% of patients were very satisfied with the drugs in use regarding convenience and perceived benefits. The only aspect scoring lesser values was tolerability. Conclusion Parameters for improving treatment in MS must include efficacy, safety, and patient satisfaction with the given DMD.

RESUMO Objetivo O tratamento da esclerose múltipla (EM) com drogas-modificadoras-da-doença (DMDs) está evoluindo e novas drogas estão sendo comercializadas. Eficácia e segurança são aspectos cruciais nas medicações, porém a satisfação do paciente com o tratamento deve ser levada em consideração. Métodos Entrevista individual com pacientes com EM investigando a satisfação e ponto de vista desta população em relação ao tratamento com DMDs. Resultados Cento e vinte e oito pacientes atendidos em unidades especializadas de EM de cinco cidades diferentes foram entrevistados. Mais de 80% dos pacientes estava bastante satisfeito com as medicações utilizadas, considerando aspectos de conveniência de uso e benefício das drogas. O único aspecto que pontuou menos foi tolerabilidade. Conclusão Parâmetros para melhor tratamento de EM devem incluir eficácia, segurança e satisfação dos pacientes com a DMD prescrita.

Flare Up Reaction During Provocation Test to Glatiramer Acetate in a Patient With Allergy to Interferon Beta1a

Glatiramer acetate (GA) is a synthetic amino acid polymer, used for relapsing-remitting multiple sclerosis. The most common adverse effect of GA is a skin reaction at the injection site with a probable IgE-mediated mechanism. We report a case of a 45-year-old woman with multiple sclerosis and urticaria to interferon-beta1a, who underwent a challenge test to GA. She presented itching wheals at the intradermal sites. A month later the patient repeated the test and presented the same reactions of the first test. The next day she continued the test with subcutaneous injections. One hour later she presented a flare up of the reactions appeared during the previous 2 tests. No reactions appeared at the subcutaneous injection sites. The patient also presented dyspnea. Flare-up reactions are characterized by the reactivation of previously positive reactions to intradermal or skin tests triggered by patch testing and after systemic provocation with an allergen. The phenomenon is not common to drugs. The mechanisms involved in this reaction seem to be heterogeneous and are not completely understood. To our knowledge this is the first case of allergic reaction to GA manifested as a flare-up reaction during challenge test.

Clinical response to interferon beta and glatiramer acetate in multiple sclerosis patients: a Brazilian cohort / Resposta terapêutica ao interferon beta e ao acetato de glatiramer em pacientes com esclerose múltipla: estudo de uma coorte brasileira

INTRODUCTION: Many patients with multiple sclerosis (MS) are currently receiving treatment with interferon beta (IFNb) and glatiramer acetate (GA). Identifying nonresponders patients is important to define therapy strategies. Several criteria for treatment response to IFNb and GA have been proposed. OBJECTIVE: It was to investigate the response to treatment with IFNb-1a, IFNb-1b and GA among relapsing-remitting multiple sclerosis (RRMS) patients. METHODS: We analyzed treatment response to IFNb and GA in ninety-one RRMS patients followed for at least one year. Clinical response was established by clinical criteria based on relapses, disability progression or both. RESULTS: We observed a proportion of nonresponders, ranging from 3.3 to 42.9%, depending on the stringency of the criteria used. CONCLUSIONS: Our sample of Brazilian patients with MS has similarities when compared to other studies and there was no statistically significant difference regarding age, gender, ethnicity or disease duration between responders and nonresponders.

INTRODUÇÃO: Muitos pacientes com esclerose múltipla (EM) estão atualmente recebendo tratamento com interferon beta (IFNb) e acetato de glatiramer (AG). Identificar pacientes não respondedores é importante para definir estratégias terapêuticas. Foram propostos vários critérios para definir a resposta ao tratamento com IFNb e AG. OBJETIVO: Foi investigar a resposta ao tratamento com IFNb-1a, IFNb-1b e AG entre pacientes com esclerose múltipla remitente-recorrente (EMRR). MÉTODOS: Analisamos a resposta ao tratamento com IFNb e AG em 91 pacientes com EMRR acompanhados por um período de pelo menos um ano. A resposta clínica foi estabelecida por critérios baseados em surtos, progressão da incapacidade ou ambos. RESULTADOS: Observamos uma proporção de não respondedores que variou de 3,3 a 42,9%, dependendo do rigor do critério utilizado. CONCLUSÕES: Nossa amostra de pacientes brasileiros com EM tem semelhanças quando comparada a outros estudos e não apresentou diferença estatisticamente significativa entre respondedores e não respondedores com relação à idade, sexo, etnia ou duração da doença.

Classical immunomodulatory therapy in multiple sclerosis: how it acts, how it works / Terapêutica imunomoduladora clássica na esclerose múltipla: como atua, como funciona

Interferon beta (IFNβ) and glatiramer acetate (GA) were the first immunomodulators approved to the treatment of relapsing-remitting multiple sclerosis (MS) and clinically isolated syndromes. Despite the enlargement of the therapeutic armamentarium, IFNβ and GA remain the most widely drugs and the therapeutic mainstay of MS. OBJECTIVE: To review the mechanisms of action of IFNβ and GA and main clinical results in MS. RESULTS: IFNβ modulates T and B-cell activity and has effects on the blood-brain barrier. The well proved mechanism of GA is an immune deviation by inducing expression of anti-inflammatory cytokines. Some authors favor the neuroprotective role of both molecules. Clinical trials showed a 30 percent reduction on the annualized relapse rate and of T2 lesions on magnetic resonance. CONCLUSION: Although the precise mechanisms how IFNβ and GA achieve their therapeutics effects remain unclear, these drugs have recognized beneficial effects and possess good safety and tolerability profiles. The large clinical experience in treating MS patients with these drugs along almost two decades deserves to be emphasized, at a time where the appearance of drugs with more selective mechanisms of action, but potentially less safer, pave the way to a better selection of the most appropriate individualized treatment.

O interferão beta (IFNβ) e o acetato de glatirâmero (GA) foram os primeiros imunomoduladores aprovados para o tratamento da esclerose múltipla (EM) surto-remissão e doentes com síndromes clinicamente isoladas. Apesar do alargamento do armamentário terapêutico, o IFNβ e o GA continuam a ser os medicamentos mais usados na EM. OBJETIVO: Rever os mecanismos de acção do IFNβ e do GA e os principais resultados na clínica. RESULTADOS: O IFNβ modula a actividade das células T e B e tem efeitos sobre a barreira hemato-encefálica. O mecanismo melhor comprovado do GA é o desvio imune através da indução da expressão de citocinas. Alguns autores favorecem ainda um papel neuroprotetor para ambos. Os ensaios clínicos mostraram diminuição da taxa anualizada de surtos de 30 por cento e das lesões em T2 na ressonância magnética. CONCLUSÃO: Embora os mecanismos pelos quais o IFNβ e o GA atingem os seus efeitos terapêuticos continuem a ser pouco claros, estes fármacos possuem efeitos benéficos reconhecidos e bons perfis de segurança e tolerabilidade. A grande experiência clínica no tratamento da EM com estes fármacos ao longo de quase duas décadas merece ser destacada, numa altura em que o aparecimento de novos fármacos com mecanismos de acção mais seletivos, mas potencialmente menos seguros, possibilitarão melhor seleção e individualização do tratamento.

Glatiramer acetate inhibits the activation of NFkappaB in the CNS of experimental autoimmune encephalomyelitis / 대한수의학회지

Glatiramer acetate (GA; Copaxone) has been shown to be effective in preventing and suppressing experimental autoimmune encephalomyelitis (EAE), the animal model of multiple sclerosis (MS). It has been recently shown that GA-reactive T cells migrate through the blood-brain barrier, accumulate in the central nervous system (CNS), secrete antiinflammatory cytokines and suppress production of proinflammatory cytokines of EAE and MS. Development of EAE requires coordinated expression of a number of genes involved in the activation and effector functions of inflammatory cells. Activation of inflammatory cells is regulated at the transcriptional level by several families of transcription factors. One of these is the nuclear factor kappa B (NFkappaB) family which is present in a variety of cell types and involved in the activation of immune-relative genes during inflammatory process. Since it is highly activated at site of inflammation, NFkappaB activation is also implicated in the pathogenesis of EAE. In this study, we examined whether the inhibition of NFkappaB activation induced by GA can have suppressive therapeutic effects in EAE mice. We observed the expression of NFkappaB and phospho-IkappaB proteins increased in GA-treated EAE mice compared to EAE control groups. The immunoreactivity in inflammatory cells and glial cells of NFkappaB and phospho-IkappaB significantly decreased at the GA-treated EAE mice. These results suggest that treatment of GA in EAE inhibits the activation of NFkappaB and phophorylation of IkappaB in the CNS. Subsequently, the inhibition of NFkappaB activation and IkappaB phosphorylation leads to the anti-inflammatory effects thereby to reduce the progression and severity of EAE.

Pregnancy and multiple sclerosis: the initial results from a Brazilian database / Gravidez e esclerose múltipla: resultados preliminares de base de dados Brasileira

PURPOSE: Pregnancy management poses an extra challenge to physicians and their multiple sclerosis (MS) patients. There are few papers reporting databases on the subject. METHOD: Brazilian database from nine MS clinical and research units, with complete data on 47 pregnant women (49 pregnancies). RESULTS: Despite relatively high exposure to MS medications, no birth defects were reported. Low birth weight and prematurity were similar to those for developing countries. Three complications may have been associated with these medications, while three others were considered to be of purely obstetric nature. CONCLUSION: Our results confirm previous findings on lower relapse rate during pregnancy and add to the present literature informing on data related to drug exposure.

PROPÓSITO: O manejo da gravidez cria um desafio extra aos médicos e aos pacientes com esclerose múltipla (EM). Existem poucos trabalhos relatando bases de dados neste tema. MÉTODO: Base de dados brasileira de nove centros clínicos e de pesquisa na EM, com dados completos de 47 mulheres grávidas (49 gestações). RESULTADOS: Apesar da exposição a drogas para EM ter sido relativamente alta, não foram registradas malformações. Baixo peso e prematuridade foram semelhantes àqueles de países em desenvolvimento. Três complicações podem ter sido associadas a drogas, enquanto outras três foram consideradas como sendo de natureza puramente obstétrica. CONCLUSÃO: Nossos resultados confirmam os achados de menor taxa de surtos na gestação e adicionam dados relacionados a exposição a drogas, na literatura atual.

The immunomodulator glatiramer acetate influences spinal motoneuron plasticity during the course of multiple sclerosis in an animal model

The immunomodulador glatiramer acetate (GA) has been shown to significantly reduce the severity of symptoms during the course of multiple sclerosis and in its animal model - experimental autoimmune encephalomyelitis (EAE). Since GA may influence the response of non-neuronal cells in the spinal cord, it is possible that, to some extent, this drug affects the synaptic changes induced during the exacerbation of EAE. In the present study, we investigated whether GA has a positive influence on the loss of inputs to the motoneurons during the course of EAE in rats. Lewis rats were subjected to EAE associated with GA or placebo treatment. The animals were sacrificed after 15 days of treatment and the spinal cords processed for immunohistochemical analysis and transmission electron microscopy. A correlation between the synaptic changes and glial activation was obtained by performing labeling of synaptophysin and glial fibrillary acidic protein using immunohistochemical analysis. Ultrastructural analysis of the terminals apposed to alpha motoneurons was also performed by electron transmission microscopy. Interestingly, although the GA treatment preserved synaptophysin labeling, it did not significantly reduce the glial reaction, indicating that inflammatory activity was still present. Also, ultrastructural analysis showed that GA treatment significantly prevented retraction of both F and S type terminals compared to placebo. The present results indicate that the immunomodulator GA has an influence on the stability of nerve terminals in the spinal cord, which in turn may contribute to its neuroprotective effects during the course of multiple sclerosis.