Spinal cord stimulation in the treatment of neuropathic pain: Current perspectives of indications, cost-effectiveness, complications and results

Introduction: The spinal cord stimulation (SCS) has been described as a valuable neuromodulating procedure in the management of chronic and medically untreated neuropathic pain. Although, many studies have discussed the use of this technique, a question still remains regarding its efficacy in different medical conditions with different etiology in the long term. The aim of this paper is to discuss the risks, complications, cost-effectiveness and results of SCS in patients affected by chronic neuropathic pain based on the comprehensive literature review. Methods: Bibliographic search of references from 1950 to 2016 using the databases MEDLINE, LILACS, SciELO, PubMed, and applied language as selection criteria, choosing preferably recent articles written in Portuguese, Spanish or English. Results: Based on literature review, SCS is a safe, reversible, adjustable and nondestructive surgical procedure demonstrating a significant effect in the reduction of pain intensity and improvement in quality of life in these patients. Furthermore, in spite of the initial high cost to its application, SCS has been associated with lower rates of complications and high rates of cost-effectiveness when compared to standard therapies. Conclusion: Although used in medical conditions with different etiology, the procedure is still an effective and a cost-effective approach to neuropathic pain, mainly in patients affected by failed back pain syndrome (FBSS) and complex regional pain syndrome (CRPS)

Consenso brasileiro para o tratamento da esclerose múltipla : Academia Brasileira de Neurologia e Comitê Brasileiro de Tratamento e Pesquisa em Esclerose Múltipla

O crescent arsenal terapêutico na esclerose múltipla (EM) tem permitido tratamentos mais efetivos e personalizados, mas a escolha e o manejo das terapias modificadoras da doença (TMDs) tem se tornado cada vez mais complexos. Neste contexto, especialistas do Comitê Brasileiro de Tratamento e Pesquisa em Esclerose Múltipla e do Departamento Científico de Neuroimunologia da Academia Brasileira de Neurologia reuniram-se para estabelecer este Consenso Brasileiro para o Tratamento da EM, baseados no entendimento de que neurologistas devem ter a possibilidade de prescrever TMDs para EM de acordo com o que é melhor para cada paciente, com base em evidências e práticas atualizadas. Por meio deste documento, propomos recomendações práticas para o tratamento da EM, com foco principal na escolha e no manejo das TMDs, e revisamos os argumentos que embasam as estratégias de tratamento na EM.The expanding therapeutic arsenal in multiple sclerosis (MS) has allowed for more effective and personalized treatment, but the choice and management of disease-modifying therapies (DMTs) is becoming increasingly complex. In this context, experts from the Brazilian Committee on Treatment and Research in Multiple Sclerosis and the Neuroimmunology Scientific Department of the Brazilian Academy of Neurology have convened to establish this Brazilian Consensus for the Treatment of MS, based on their understanding that neurologists should be able to prescribe MS DMTs according to what is better for each patient, based on up-to-date evidence and practice. We herein propose practical recommendations for the treatment of MS, with the main focus on the choice and management of DMTs, as well as present a review of the scientific rationale supporting therapeutic strategies in MS

Spinal cord stimulation in the treatment of neuropathic pain: Current perspectives of indications, cost-effectiveness, complications and results

Introduction: The spinal cord stimulation (SCS) has been described as a valuable neuromodulating procedure in the management of chronic and medically untreated neuropathic pain. Although, many studies have discussed the use of this technique, a question still remains regarding its efficacy in different medical conditions with different etiology in the long term. The aim of this paper is to discuss the risks, complications, cost-effectiveness and results of SCS in patients affected by chronic neuropathic pain based on the comprehensive literature review. Methods: Bibliographic search of references from 1950 to 2016 using the databases MEDLINE, LILACS, SciELO, PubMed, and applied language as selection criteria, choosing preferably recent articles written in Portuguese, Spanish or English. Results: Based on literature review, SCS is a safe, reversible, adjustable and nondestructive surgical procedure demonstrating a significant effect in the reduction of pain intensity and improvement in quality of life in these patients. Furthermore, in spite of the initial high cost to its application, SCS has been associated with lower rates of complications and high rates of cost-effectiveness when compared to standard therapies. Conclusion: Although used in medical conditions with different etiology, the procedure is still an effective and a cost-effective approach to neuropathic pain, mainly in patients affected by failed back pain syndrome (FBSS) and complex regional pain syndrome (CRPS)

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

Long-term efficacy and safety of alemtuzumab in patients with RRMS: 12-year follow-up of CAMMS223

Funder: Sanofi; doi: http://dx.doi.org/10.13039/100004339Funder: Bayer Healthcare PharmaceuticalsAbstract: Background: In the phase 2 CAMMS223 trial (NCT00050778), alemtuzumab significantly improved clinical and MRI outcomes versus subcutaneous interferon beta-1a over 3 years in treatment-naive patients with relapsing–remitting MS. Here, we assess efficacy and safety of alemtuzumab over 12 years in CAMMS223 patients who enrolled in the CAMMS03409 extension (NCT00930553), with available follow-up through the subsequent TOPAZ extension (NCT02255656). Methods: In CAMMS223, patients received 2 alemtuzumab courses (12 mg/day; baseline: 5 days; 12 months later: 3 days); 22% received a third course. In the open-label, nonrandomized extensions, patients could receive as-needed additional alemtuzumab or other disease-modifying therapies. Results: Of 108 alemtuzumab-treated patients in CAMMS223, 60 entered the CAMMS03409 extension; 33% received a total of 2 alemtuzumab courses, and 73% received no more than 3 courses through Year 12. Over 12 years, annualized relapse rate was 0.09, 71% of patients had stable or improved Expanded Disability Status Scale scores, and 69% were free of 6-month confirmed disability worsening. In Year 12, 73% of patients were free of MRI disease activity. Cumulatively throughout the extensions (Years 7–12), 34% of patients had no evidence of disease activity. Adverse event (AE) incidence declined through Year 12. Infusion-associated reactions peaked at first course and declined thereafter. Cumulative thyroid AE incidence was 50%; one immune thrombocytopenia event occurred, and there were no autoimmune nephropathy cases. Conclusions: Alemtuzumab efficacy was maintained over 12 years in CAMMS223 patients, with 73% receiving no more than three courses. The safety profile in this cohort was consistent with other alemtuzumab clinical trials

Pregnancy outcomes and postpartum relapse rates in women with RRMS treated with alemtuzumab in the phase 2 and 3 clinical development program over 16 years

Background Relapsing-remitting multiple sclerosis (RRMS) is frequently diagnosed in women of reproductive age. Because the use of disease-modifying therapies (DMTs) early in the disease course is increasing, it is important to evaluate the safety of DMTs in pregnant women and their developing fetuses. Alemtuzumab, approved for the treatment of relapsing forms of MS, is administered as 2 courses of 12 mg/day on 5 consecutive days at baseline and on 3 consecutive days 12 months later. Alemtuzumab is eliminated from the body within approximately 30 days after administration; it is recommended that women of childbearing potential use effective contraception during and for 4 months after treatment. Here, we report pregnancy outcomes in alemtuzumab-treated women from the phase 2 and 3 clinical development program over 16 years. Methods We followed 972 women who had alemtuzumab in phase 2 (CAMMS223 [NCT00050778]) and phase 3 (CARE-MS I [NCT00530348], CARE-MS II [NCT00548405]) studies, and/or in 2 consecutive extension studies (NCT00930553; NCT02255656 [TOPAZ]). In the extension studies, patients could receive additional alemtuzumab (12 mg/day on 3 days; ≥12 months apart) as needed for disease activity. All women who received alemtuzumab in the clinical development program were included. Pregnant or lactating patients were followed up for safety. Results As of November 26, 2018, 264 pregnancies occurred in 160 alemtuzumab-treated women, with a mean age at conception of 32.6 years, and mean time from last alemtuzumab dose to conception of 35.9 months. Of the 264 pregnancies, 233 (88%) were completed, 11 (4%) were ongoing, and 20 (8%) had unknown outcomes; 16 (6%) conceptions occurred within 4 months, and 5 conceptions within 1 month of the last alemtuzumab dose. Of the 233 completed pregnancies with known outcomes, there were 155 (67%) live births with no congenital abnormalities or birth defects, 52 (22%) spontaneous abortions, 25 (11%) elective abortions, and 1 (0.4%) stillbirth. Maternal age was associated with an increased risk of spontaneous abortion in alemtuzumab-treated patients (4 months since alemtuzumab exposure (19% vs 23%; RR, 1.08 [95% CI: 0.41–2.85], p=0.88). Autoimmune thyroid adverse events did not increase risk for spontaneous abortion (patients with vs without thyroid adverse events, 23.7% vs 21.3%; RR, 1.11 [95% CI: 0.69–1.80], p=0.75). Annualized relapse rate was 0.10 and 0.12 in the 2 years prior to pregnancy (post alemtuzumab), and was 0.22, 0.12, and 0.12 in each of the first 3 years postpartum, respectively. Conclusion Normal live births were the most common outcome in women exposed to alemtuzumab 12 mg or 24 mg in clinical studies. Spontaneous abortion rate in alemtuzumab-treated patients was comparable with rates in the general population and treatment-naive MS patients, and was not increased in women with pregnancy onset within 4 months of alemtuzumab exposure. There was a minimal increase in postpartum relapses