Natalizumab treatment in multiple sclerosis: the experience from two Brazilian MS centers Natalizumabe no tratamento da esclerose múltipla: a experiência de dois centros brasileiros

Multiple sclerosis (MS) is a demyelinating, inflammatory disease of the central nervous system (CNS), presumably with an autoimmune etiopathogenesis. The first line therapies developed for the relapsing-remitting form of MS (RRMS) include disease modifying treatments (DMTs) as interferons (IFNs) beta and glatiramer acetate (GA) and they are known to be partially effective, with 20 -50% of treated patients experiencing a relapse or disability progression in a short period of time 1 . Natalizumab is a humanized monoclonal antibody that blocks the α-4 integrin, VLA-4, an adhesion molecule present on leukocytes surface, inhibiting their migration into CNS 2 . In the pivotal study AFFIRM, natalizumab reduced annualized relapse rate (aRR) by 68% and the risk of sustained disability progression by 42% over 2 years 2 . Although patients studied in AFFIRM were mostly treatment naïve RRMS patients, natalizumab is only approved for use in patient that failed treatment with DMTs or have highly active disease. This more restricted use of natalizumab is consequence of safety concerns related to risk of progressive multifocal leukoencephalopathy (PML), a rare but potentially life-threatening ABSTRACT Objective: Analyze the demographics, clinical characteristics, efficacy and safety of natalizumab treatment in Brazilian patients with multiple sclerosis (MS) followed up for at least 12 months, in two tertiary MS care centers in São Paulo. Method: We evaluated the effect of natalizumab treatment on annualized relapse rate and disability progression in 75 patients with MS treated with natalizumab for at least 12 months. A subgroup analysis was performed to evaluate efficacy of natalizumab treatment in patients with Expanded Disability Status Scale (EDSS) ≤ 3.0 vs patients with EDSS > 3. Results: Patients treated for at least one year with natalizumab showed a 91% reduction in aRR, as well and an improvement in neurological disability. The impact of natalizumab treatment was greater in patients with EDSS < 3.0. Overall, natalizumab was safe but one patient developed progressive multifocal leukoencephalopathy. Conclusion: Natalizumab as a third line therapy is safe and efficacious, especially in patients with mild neurological disability. Keywords: natalizumab, multiple sclerosis, disability progression, relapse rate. RESUMO Objetivo: Analisar as características clínicas e demográficas, assim como a eficácia e segurança do tratamento com natalizumabe (usado em terceira linha), por no mínimo 12 meses, em pacientes brasileiros acompanhados em dois centros de tratamento de esclerose múltipla, na cidade de São Paulo. Método: Avaliamos o efeito do tratamento com natalizumabe na taxa anualizada de surto (aRR) e progressão de incapacidade (medida por Expanded Disability Status Scale (EDSS)) em 75 pacientes tratados por, no mínimo 12 meses. Realizamos uma análise de subgrupo em pacientes com EDSS ≤ 3,0 e com EDSS > 3, para avaliar o impacto no tratamento, considerando-se o grau de incapacidade neurológica. Resultados: O tratamento com natalizumabe, por pelo menos um ano, reduziu a aRR em 91%, assim como melhorou a incapacidade neurológica. Em pacientes com EDSS ≤ 3,0 observamos um impacto maior do tratamento na incapacidade neurológica, reduzindo sua progressão em 51%, durante o período do estudo. O tratamento com natalizumabe é seguro, porém um paciente desenvolveu leucoencefalopatia multifocal progressiva. Conclusão: O tratamento com natalizumabe, em terceira linha terapêutica é seguro e eficaz especialmente, em pacientes com incapacidade neurológica leve (EDSS ≤ 3.0). Palavras-chave: natalizumabe, esclerose múltipla, progressão da incapacidade, taxa de surto

Natalizumab treatment in multiple sclerosis: the experience from two Brazilian MS centers

Objective Analyze the demographics, clinical characteristics, efficacy and safety of natalizumab treatment in Brazilian patients with multiple sclerosis (MS) followed up for at least 12 months, in two tertiary MS care centers in São Paulo.Method We evaluated the effect of natalizumab treatment on annualized relapse rate and disability progression in 75 patients with MS treated with natalizumab for at least 12 months. A subgroup analysis was performed to evaluate efficacy of natalizumab treatment in patients with Expanded Disability Status Scale (EDSS) ≤ 3.0 vs patients with EDSS > 3.Results Patients treated for at least one year with natalizumab showed a 91% reduction in aRR, as well and an improvement in neurological disability. The impact of natalizumab treatment was greater in patients with EDSS < 3.0. Overall, natalizumab was safe but one patient developed progressive multifocal leukoencephalopathy.Conclusion Natalizumab as a third line therapy is safe and efficacious, especially in patients with mild neurological disability