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3.
N Engl J Med ; 383(17): 1645-1656, 2020 10 22.
Artigo em Inglês | MEDLINE | ID: mdl-33026741

RESUMO

BACKGROUND: Whether combined treatment with recombinant interferon beta-1b and lopinavir-ritonavir reduces mortality among patients hospitalized with Middle East respiratory syndrome (MERS) is unclear. METHODS: We conducted a randomized, adaptive, double-blind, placebo-controlled trial that enrolled patients at nine sites in Saudi Arabia. Hospitalized adults with laboratory-confirmed MERS were randomly assigned to receive recombinant interferon beta-1b plus lopinavir-ritonavir (intervention) or placebo for 14 days. The primary outcome was 90-day all-cause mortality, with a one-sided P-value threshold of 0.025. Prespecified subgroup analyses and safety analyses were conducted. Because of the pandemic of coronavirus disease 2019, the data and safety monitoring board requested an unplanned interim analysis and subsequently recommended the termination of enrollment and the reporting of the results. RESULTS: A total of 95 patients were enrolled; 43 patients were assigned to the intervention group and 52 to the placebo group. A total of 12 patients (28%) in the intervention group and 23 (44%) in the placebo group died by day 90. The analysis of the primary outcome, with accounting for the adaptive design, yielded a risk difference of -19 percentage points (upper boundary of the 97.5% confidence interval [CI], -3; one-sided P = 0.024). In a prespecified subgroup analysis, treatment within 7 days after symptom onset led to lower 90-day mortality than use of placebo (relative risk, 0.19; 95% CI, 0.05 to 0.75), whereas later treatment did not. Serious adverse events occurred in 4 patients (9%) in the intervention group and in 10 (19%) in the placebo group. CONCLUSIONS: A combination of recombinant interferon beta-1b and lopinavir-ritonavir led to lower mortality than placebo among patients who had been hospitalized with laboratory-confirmed MERS. The effect was greatest when treatment was started within 7 days after symptom onset. (Funded by the King Abdullah International Medical Research Center; MIRACLE ClinicalTrials.gov number, NCT02845843.).


Assuntos
Infecções por Coronavirus/tratamento farmacológico , Interferon beta-1b/uso terapêutico , Lopinavir/uso terapêutico , Ritonavir/uso terapêutico , Administração Oral , Adulto , Idoso , Infecções por Coronavirus/mortalidade , Método Duplo-Cego , Combinação de Medicamentos , Quimioterapia Combinada , Feminino , Hospitalização , Humanos , Injeções Subcutâneas , Interferon beta-1b/efeitos adversos , Estimativa de Kaplan-Meier , Lopinavir/efeitos adversos , Masculino , Pessoa de Meia-Idade , Ritonavir/efeitos adversos , Estatísticas não Paramétricas , Tempo para o Tratamento
4.
Int Immunopharmacol ; 88: 106903, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32862111

RESUMO

In this study, efficacy and safety of interferon (IFN) ß-1b in the treatment of patients with severe COVID-19 were evaluated. Among an open-label, randomized clinical trial, adult patients (≥18 years old) with severe COVID-19 were randomly assigned (1:1) to the IFN group or the control group. Patients in the IFN group received IFN ß-1b (250 mcg subcutaneously every other day for two consecutive weeks) along with the national protocol medications while in the control group, patients received only the national protocol medications (lopinavir/ritonavir or atazanavir/ritonavir plus hydroxychloroquine for 7-10 days). The primary outcome of the study was time to clinical improvement. Secondary outcomes were in-hospital complications and 28-daymortality. Between April 20 and May 20, 2020, 80 patients were enrolled and finally 33 patients in each group completed the study. Time to clinical improvment in the IFN group was significantly shorter than the control group ([9(6-10) vs. 11(9-15) days respectively, p = 0.002, HR = 2.30; 95% CI: 1.33-3.39]). At day 14, the percentage of discharged patients was 78.79% and 54.55% in the IFN and control groups respectively (OR = 3.09; 95% CI: 1.05-9.11, p = 0.03). ICU admission rate in the control group was significantly higher than the IFN group (66.66% vs. 42.42%, p = 0.04). The duration of hospitalization and ICU stay were not significantly different between the groups All-cause 28-day mortality was 6.06% and 18.18% in the IFN and control groups respectively (p = 0.12). IFN ß-1b was effective in shortening the time to clinical improvement without serious adverse events in patients with severe COVID-19. Furthermore, admission in ICU and need for invasive mechanical ventilation decreased following administration of IFN ß-1b. Although 28-day mortality was lower in the IFN group, further randomized clinical trials with large sample size are needed for exact estimation of survival benefit of IFN ß-1b.


Assuntos
Antivirais/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Interferon beta-1b/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Idoso , Antivirais/administração & dosagem , Antivirais/efeitos adversos , Betacoronavirus , Infecções por Coronavirus/imunologia , Esquema de Medicação , Quimioterapia Combinada , Feminino , Humanos , Injeções Subcutâneas , Interferon beta-1b/administração & dosagem , Interferon beta-1b/efeitos adversos , Estimativa de Kaplan-Meier , Masculino , Metilprednisolona/administração & dosagem , Metilprednisolona/uso terapêutico , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/imunologia , Índice de Gravidade de Doença , Resultado do Tratamento
5.
Am J Trop Med Hyg ; 103(4): 1364-1366, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32828137

RESUMO

As the global COVID-19 pandemic continues, unabated and clinical trials demonstrate limited effective pharmaceutical interventions, there is a pressing need to accelerate treatment evaluations. Among options for accelerated development is the evaluation of drug combinations in the absence of prior monotherapy data. This approach is appealing for a number of reasons. First, combining two or more drugs with related or complementary therapeutic effects permits a multipronged approach addressing the variable pathways of the disease. Second, if an individual component of a combination offers a therapeutic effect, then in the absence of antagonism, a trial of combination therapy should still detect individual efficacy. Third, this strategy is time saving. Rather than taking a stepwise approach to evaluating monotherapies, this strategy begins with testing all relevant therapeutic options. Finally, given the severity of the current pandemic and the absence of treatment options, the likelihood of detecting a treatment effect with combination therapy maintains scientific enthusiasm for evaluating repurposed treatments. Antiviral combination selection can be facilitated by insights regarding SARS-CoV-2 pathophysiology and cell cycle dynamics, supported by infectious disease and clinical pharmacology expert advice. We describe a clinical evaluation strategy using adaptive combination platform trials to rapidly test combination therapies to treat COVID-19.


Assuntos
Antivirais/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/epidemiologia , Quimioterapia Combinada/métodos , Projetos de Pesquisa Epidemiológica , Pandemias , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/epidemiologia , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/imunologia , Betacoronavirus/patogenicidade , Ensaios Clínicos como Assunto , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Combinação de Medicamentos , Reposicionamento de Medicamentos/métodos , Humanos , Interferon beta-1b/uso terapêutico , Lopinavir/uso terapêutico , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Ribavirina/uso terapêutico , Ritonavir/uso terapêutico
7.
Trials ; 21(1): 473, 2020 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-32493468

RESUMO

OBJECTIVES: We will investigate the effectiveness of Interferon Beta 1a, compared to Interferon Beta 1b and the usual therapeutic regimen in COVID-19 in patients that have tested positive and are moderately to severely ill. TRIAL DESIGN: This is a single center, open label, randomized, controlled, parallel group, clinical trial that will be conducted at Loghman Hakim Medical Education Center in conjunction with Shahid Beheshti University of Medical Sciences. PARTICIPANTS: Sixty COVID-19 confirmed cases (using the RT-PCR test) will be enrolled in the trial between April 9th to April 14th 2020. Patients will be randomly assigned to the intervention groups or the control group with the following eligibility criteria: ≥ 18 years of age AND (oxygen saturation (SPO2) ≤ 93% OR respiratory rate ≥ 24) AND at least one of the following: Contactless infrared forehead thermometer temperature of ≥37.8, cough, sputum production, nasal discharge, myalgia, headache or fatigue on admission, and time of onset of the symptoms should be acute (Days ≤ 14). Although Hydroxychloroquine will be administered in a single dose, patients with heart problems (prolonged QT or PR intervals, second- or third-degree heart block, and arrhythmias including torsade de pointes) will be excluded. Other exclusion criteria include using drugs with potential interaction with Hydroxychloroquine + Lopinavir/Ritonavir, Interferon-ß 1a, Interferon-ß 1b, pregnant or lactating women, history of alcohol or drug addiction in the past 5 years, blood ALT/AST levels > 5 times the upper limit of normal on laboratory results and refusal to participate. This study will be undertaken at the Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences and Health Services. INTERVENTION AND COMPARATOR: COVID-19 confirmed patients will be randomly assigned to one of three groups, with 20 patients in each. The first group (Arm 1) will receive Hydroxychloroquine + Lopinavir / Ritonavir (Kaletra) + Interferon-ß 1a (Recigen), the second group (Arm 2) will be administered Hydroxychloroquine + Lopinavir / Ritonavir (Kaletra) + Interferon-ß 1b (Ziferon), and the control group (Arm 3) will be treated by Hydroxychloroquine + Lopinavir / Ritonavir (Kaletra). MAIN OUTCOMES: Time to clinical improvement is our primary outcome measure. This is an improvement of two points on a seven-category ordinal scale (recommended by the World Health Organization: Coronavirus disease (COVID-2019) R&D. Geneva: World Health Organization) or discharge from the hospital, whichever comes first. Secondary outcomes include mortality from the date of randomization until the last day of the study which will be the day all of the patients have had at least one of the following outcomes: 1) Improvement of two points on a seven-category ordinal scale. 2) Discharge from the hospital 3) Death. If any patient dies, we have reached an important secondary outcome. SpO2 Improvement between the last and first day of hospitalization, using pulse-oximetry. Duration of hospitalization from date of randomization until the date of hospital discharge or date of death from any cause, whichever comes first. Incidence of new mechanical ventilation uses from date of randomization until the last day of the study. Please note that we are trying to add further secondary outcomes and this section of the protocol is still evolving. Statistical analysis will be performed by R version 3.6.1 software. We will use Kaplan-Meier to analyze the time to clinical improvement (compared with a log-rank test). Hazard ratios with 95% confidence intervals will be calculated using the Cox proportional-hazards model in crude and adjusted analysis. RANDOMIZATION: Eligible patients will be randomly assigned in a 1:1:1 ratio to receive either Interferon Beta 1a, Interferon Beta 1b or standard care only. Patients will be randomly allocated to three therapeutic arms using permuted, block-randomization to balance the number of patients allocated to each group. The permuted block (three or six patients per block) randomization sequence will be generated, using Package 'randomizeR' in R software version 3.6.1. and placed in individual sealed and opaque envelopes by the statistician. The investigator will enroll the patients and only then open envelopes to assign patients to the different treatment groups. This method of allocation concealment will result in minimum selection and confounding biases. BLINDING (MASKING): The present research is open-label (no masking) of patients and health care professionals who are undertaking outcome assessment of the primary outcome - time to clinical improvement. NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): Of the 60 patients who underwent randomization, 20 patients were assigned to receive Interferon beta-1a, 20 patients were assigned to receive Interferon beta 1b plus standard care and the rest of patients were assigned to receive the standard care alone. TRIAL STATUS: Protocol version 1.2.1. Recruitment is finished, the start date of recruitment was on 9th April 2020 and the end date was on 14th April 2020. Last point of data collection will be the last day on which all of the 60 participants have had an outcome of clinical improvement or death, completing the study's follow-up time window. TRIAL REGISTRATION: This study was registered with National Institutes of Health Clinical trials (www.clinicaltrials.gov; identification number NCT04343768, registered April 8, 2020 and first available online April 13, 2020). FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


Assuntos
Antivirais/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Interferon beta-1a/uso terapêutico , Interferon beta-1b/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Antivirais/efeitos adversos , Betacoronavirus/patogenicidade , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/virologia , Combinação de Medicamentos , Quimioterapia Combinada , Interações Hospedeiro-Patógeno , Humanos , Hidroxicloroquina/uso terapêutico , Interferon beta-1a/efeitos adversos , Interferon beta-1b/efeitos adversos , Irã (Geográfico) , Lopinavir/uso terapêutico , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/virologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Ritonavir/uso terapêutico , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento
8.
Infez Med ; 28(suppl 1): 52-56, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32532939

RESUMO

In spite of many ongoing attempts to repurpose existing antivirals, no drugs have emerged yet with the desirable activity against SARS-CoV-2. Hydroxychloroquine, lopinavir/ritonavir, remdesivir, umifenovir, favipiravir, ribavirin and beta-interferon-1 gave rise to variable but still inconsistent proof of clinical efficacy in the treatment of COVID-19. Pathogenetic studies have shown significant differences between commonly defined viral pneumonia and COVID-19 pulmonary disease. In severe forms, immune/inflammatory alterations reminiscent of disease forms like Macrophage Activation Syndrome (MAS) have been described, and therapeutic options other than anti-infective have been proposed and implemented, such as anti-inflammatory and anticoagulative agents. The thrombotic phenomena described in the pulmonary vascular bed of patients with severe COVID-19 suggest the administration of low-molecular weight heparin (LMWH) as standard measure in hospitalized patients with COVID-19.


Assuntos
Anticoagulantes/uso terapêutico , Infecções por Coronavirus/complicações , Cuidados Críticos/métodos , Heparina de Baixo Peso Molecular/uso terapêutico , Pneumonia Viral/complicações , Trombofilia/tratamento farmacológico , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/uso terapêutico , Alanina/análogos & derivados , Alanina/uso terapêutico , Anticoagulantes/administração & dosagem , Antivirais/administração & dosagem , Antivirais/uso terapêutico , Biomarcadores , Infecções por Coronavirus/sangue , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/fisiopatologia , Gerenciamento Clínico , Método Duplo-Cego , Combinação de Medicamentos , Quimioterapia Combinada , Embolia/epidemiologia , Embolia/prevenção & controle , Endotélio Vascular/fisiopatologia , Heparina de Baixo Peso Molecular/administração & dosagem , Humanos , Hidroxicloroquina/uso terapêutico , Interferon beta-1b/uso terapêutico , Lopinavir/uso terapêutico , Ativação de Macrófagos , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/fisiopatologia , Fibrose Pulmonar/etiologia , Fibrose Pulmonar/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como Assunto , Ritonavir/uso terapêutico , Tromboembolia/epidemiologia , Tromboembolia/prevenção & controle , Trombofilia/sangue , Trombofilia/etiologia , Trombose/epidemiologia , Trombose/prevenção & controle
9.
Brasília; s.n; 17 jun. 2020.
Não convencional em Português | LILACS, BRISA/RedTESA, PIE | ID: biblio-1100423

RESUMO

O Informe Diário de Evidências é uma produção do Ministério da Saúde que tem como objetivo acompanhar diariamente as publicações científicas sobre tratamento farmacológico e vacinas para a COVID-19. Dessa forma, são realizadas buscas estruturadas em bases de dados biomédicas, referente ao dia anterior desse informe. Não são incluídos estudos pré-clínicos (in vitro, in vivo, in silico). A frequência dos estudos é demonstrada de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, coortes, entre outros). Para cada estudo é apresentado um resumo com avaliação da qualidade metodológica. Essa avaliação tem por finalidade identificar o grau de certeza/confiança ou o risco de viés de cada estudo. Para tal, são utilizadas ferramentas já validadas e consagradas na literatura científica, na área de saúde baseada em evidências. Cabe ressaltar que o documento tem caráter informativo e não representa uma recomendação oficial do Ministério da Saúde sobre a temática. Foram encontrados 15 artigos.


Assuntos
Humanos , Pneumonia Viral/tratamento farmacológico , Infecções por Coronavirus/tratamento farmacológico , Betacoronavirus/efeitos dos fármacos , Avaliação da Tecnologia Biomédica , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Heparina/uso terapêutico , Lincomicina/uso terapêutico , Azitromicina/uso terapêutico , Ritonavir/uso terapêutico , Bloqueadores do Receptor Tipo 2 de Angiotensina II/uso terapêutico , Lopinavir/uso terapêutico , Interferon beta-1a/uso terapêutico , Interferon beta-1b/uso terapêutico , Interferon alfa-2/uso terapêutico , Hidroxicloroquina/uso terapêutico , Medicina Tradicional Chinesa , Antibacterianos/uso terapêutico , Antimaláricos/uso terapêutico , Óxido Nítrico/uso terapêutico
10.
Lancet ; 395(10238): 1695-1704, 2020 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-32401715

RESUMO

BACKGROUND: Effective antiviral therapy is important for tackling the coronavirus disease 2019 (COVID-19) pandemic. We assessed the efficacy and safety of combined interferon beta-1b, lopinavir-ritonavir, and ribavirin for treating patients with COVID-19. METHODS: This was a multicentre, prospective, open-label, randomised, phase 2 trial in adults with COVID-19 who were admitted to six hospitals in Hong Kong. Patients were randomly assigned (2:1) to a 14-day combination of lopinavir 400 mg and ritonavir 100 mg every 12 h, ribavirin 400 mg every 12 h, and three doses of 8 million international units of interferon beta-1b on alternate days (combination group) or to 14 days of lopinavir 400 mg and ritonavir 100 mg every 12 h (control group). The primary endpoint was the time to providing a nasopharyngeal swab negative for severe acute respiratory syndrome coronavirus 2 RT-PCR, and was done in the intention-to-treat population. The study is registered with ClinicalTrials.gov, NCT04276688. FINDINGS: Between Feb 10 and March 20, 2020, 127 patients were recruited; 86 were randomly assigned to the combination group and 41 were assigned to the control group. The median number of days from symptom onset to start of study treatment was 5 days (IQR 3-7). The combination group had a significantly shorter median time from start of study treatment to negative nasopharyngeal swab (7 days [IQR 5-11]) than the control group (12 days [8-15]; hazard ratio 4·37 [95% CI 1·86-10·24], p=0·0010). Adverse events included self-limited nausea and diarrhoea with no difference between the two groups. One patient in the control group discontinued lopinavir-ritonavir because of biochemical hepatitis. No patients died during the study. INTERPRETATION: Early triple antiviral therapy was safe and superior to lopinavir-ritonavir alone in alleviating symptoms and shortening the duration of viral shedding and hospital stay in patients with mild to moderate COVID-19. Future clinical study of a double antiviral therapy with interferon beta-1b as a backbone is warranted. FUNDING: The Shaw-Foundation, Richard and Carol Yu, May Tam Mak Mei Yin, and Sanming Project of Medicine.


Assuntos
Infecções por Coronavirus/tratamento farmacológico , Interferon beta-1b/uso terapêutico , Lopinavir/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Ribavirina/uso terapêutico , Ritonavir/uso terapêutico , Adulto , Betacoronavirus , Combinação de Medicamentos , Quimioterapia Combinada , Feminino , Hong Kong , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias
11.
Brasília; s.n; 11 maio 2020.
Não convencional em Português | LILACS, BRISA/RedTESA, PIE | ID: biblio-1097395

RESUMO

Essa é uma produção do Departamento de Ciência e Tecnologia (Decit) da Secretaria de Ciência, Tecnologia, Inovação e Insumos Estratégicos em Saúde (SCTIE) do Ministério da Saúde (Decit/SCTIE/MS), que tem como missão promover a ciência e tecnologia e o uso de evidências científicas para a tomada de decisão do SUS, tendo como principal atribuição o incentivo ao desenvolvimento de pesquisas em saúde no Brasil, de modo a direcionar os investimentos realizados em pesquisa pelo Governo Federal às necessidades de saúde pública. Informar sobre as principais evidências científicas descritas na literatura internacional sobre tratamento farmacológico para a COVID-19. Além de resumir cada estudo identificado, o informe apresenta também uma avaliação da qualidade metodológica e a quantidade de artigos publicados, de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, entre outros). Foram encontrados 16 artigos e 17 protocolos.


Assuntos
Humanos , Pneumonia Viral/tratamento farmacológico , Infecções por Coronavirus/tratamento farmacológico , Progressão da Doença , Betacoronavirus/efeitos dos fármacos , Ácido Ascórbico/uso terapêutico , Ribavirina/uso terapêutico , Metilprednisolona/uso terapêutico , Cloroquina/uso terapêutico , Corticosteroides/uso terapêutico , Azitromicina/uso terapêutico , Ritonavir/uso terapêutico , Combinação de Medicamentos , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Lopinavir/uso terapêutico , Interferon beta-1b/uso terapêutico , Glucocorticoides/uso terapêutico , Hidroxicloroquina/uso terapêutico
12.
Neurology ; 94(18): e1950-e1960, 2020 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-32300060

RESUMO

OBJECTIVE: To investigate whether vitamin D, smoking, and anti-Epstein-Barr virus (EBV) antibody concentrations predict long-term cognitive status and neuroaxonal injury in multiple sclerosis (MS). METHODS: This study was conducted among 278 patients with clinically isolated syndrome who participated in the clinical trial BENEFIT (Betaferon/Betaseron in Newly Emerging Multiple Sclerosis for Initial Treatment) and completed the 11-year assessment (BENEFIT-11). We measured serum 25-hydroxyvitamin-D (25(OH)D), cotinine (smoking biomarker), and anti-Epstein-Barr virus nuclear antigen 1 (EBNA-1) immunoglobulin G (IgG) at baseline and at months 6, 12, and 24 and examined whether these biomarkers contributed to predict Paced Auditory Serial Addition Test (PASAT)-3 scores and serum neurofilament light chain (NfL) concentrations at 11 years. Linear and logistic regression models were adjusted for sex, baseline age, treatment allocation, steroid treatment, multifocal symptoms, T2 lesions, and body mass index. RESULTS: Higher vitamin D predicted better, whereas smoking predicted worse cognitive performance. A 50-nmol/L higher mean 25(OH)D in the first 2 years was related to 65% lower odds of poorer PASAT performance at year 11 (95% confidence intervals [95% CIs]: 0.14-0.89). Standardized PASAT scores were lower in smokers and heavy smokers than nonsmokers (p trend = 0.026). Baseline anti-EBNA-1 IgG levels did not predict cognitive performance (p trend = 0.88). Associations with NfL concentrations at year 11 corroborated these findings-a 50-nmol/L higher mean 25(OH)D in the first 2 years was associated with 20% lower NfL (95% CI: -36% to 0%), whereas smokers had 20% higher NfL levels than nonsmokers (95% CI: 2%-40%). Anti-EBNA-1 antibodies were not associated with NfL. CONCLUSIONS: Lower vitamin D and smoking after clinical onset predicted worse long-term cognitive function and neuronal integrity in patients with MS.


Assuntos
Biomarcadores/sangue , Cognição , Esclerose Múltipla Recidivante-Remitente/complicações , Fumar/efeitos adversos , Vitamina D/análogos & derivados , Adjuvantes Imunológicos/uso terapêutico , Anticorpos Antivirais/sangue , Cotinina/sangue , Doenças Desmielinizantes/tratamento farmacológico , Método Duplo-Cego , Infecções por Vírus Epstein-Barr/sangue , Feminino , Seguimentos , Humanos , Interferon beta-1b/uso terapêutico , Masculino , Esclerose Múltipla Recidivante-Remitente/sangue , Esclerose Múltipla Recidivante-Remitente/patologia , Proteínas de Neurofilamentos/sangue , Fatores de Risco , Fumar/sangue , Tempo , Vitamina D/sangue
13.
BMC Neurol ; 20(1): 75, 2020 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-32126977

RESUMO

BACKGROUND: Neuroprotection and promotion of remyelination represent important therapeutic gaps in multiple sclerosis (MS). Acute optic neuritis (ON) is a frequent MS manifestation. Based on the presence and properties of sphingosine-1-phosphate receptors (S1PR) on astrocytes and oligodendrocytes, we hypothesized that remyelination can be enhanced by treatment with fingolimod, a S1PR modulator currently licensed for relapsing-remitting MS. METHODS: MOVING was an investigator-driven, rater-blind, randomized clinical trial. Patients with acute unilateral ON, occurring as a clinically isolated syndrome or MS relapse, were randomized to 6 months of treatment with 0.5 mg oral fingolimod or subcutaneous IFN-ß 1b 250 µg every other day. The change in multifocal visual evoked potential (mfVEP) latency of the qualifying eye was examined as the primary (month 6 vs. baseline) and secondary (months 3, 6 and 12 vs. baseline) outcome. In addition, full field visual evoked potentials, visual acuity, optical coherence tomography as well as clinical relapses and measures of disability, cerebral MRI, and self-reported visual quality of life were obtained for follow-up. The study was halted due to insufficient recruitment (n = 15), and available results are reported. RESULTS: Per protocol analysis of the primary endpoint revealed a significantly larger reduction of mfVEP latency at 6 months compared to baseline with fingolimod treatment (n = 5; median decrease, 15.7 ms) than with IFN-ß 1b treatment (n = 4; median increase, 8.15 ms) (p <  0.001 for interaction). Statistical significance was maintained in the secondary endpoint analysis. Descriptive results are reported for other endpoints. CONCLUSION: Preliminary results of the MOVING trial argue in support of a beneficial effect of fingolimod on optic nerve remyelination when compared to IFN-ß treatment. Interpretation is limited by the small number of complete observations, an unexpected deterioration of the control group and a difference in baseline mfVEP latencies. The findings need to be confirmed in larger studies. TRIAL REGISTRATION: The trial was registered as EUDRA-CT 2011-004787-30 on October 26, 2012 and as NCT01647880 on July 24, 2012.


Assuntos
Cloridrato de Fingolimode/uso terapêutico , Imunossupressores/uso terapêutico , Neurite Óptica/tratamento farmacológico , Adulto , Potenciais Evocados Visuais/efeitos dos fármacos , Feminino , Humanos , Interferon beta-1b/uso terapêutico , Masculino , Pessoa de Meia-Idade
14.
Trials ; 21(1): 8, 2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31900204

RESUMO

The MIRACLE trial (MERS-CoV Infection tReated with A Combination of Lopinavir/ritonavir and intErferon-ß1b) investigates the efficacy of a combination therapy of lopinavir/ritonavir and recombinant interferon-ß1b provided with standard supportive care, compared to placebo provided with standard supportive care, in hospitalized patients with laboratory-confirmed MERS. The MIRACLE trial is designed as a recursive, two-stage, group sequential, multicenter, placebo-controlled, double-blind randomized controlled trial. The aim of this article is to describe the statistical analysis plan for the MIRACLE trial. The primary outcome is 90-day mortality. The primary analysis will follow the intention-to-treat principle. The MIRACLE trial is the first randomized controlled trial for MERS treatment. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02845843. Registered on 27 July 2016.


Assuntos
Antivirais/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Interferon beta-1b/uso terapêutico , Lopinavir/uso terapêutico , Coronavírus da Síndrome Respiratória do Oriente Médio/efeitos dos fármacos , Ritonavir/uso terapêutico , Antivirais/efeitos adversos , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/virologia , Interpretação Estatística de Dados , Método Duplo-Cego , Combinação de Medicamentos , Interações Hospedeiro-Patógeno , Humanos , Interferon beta-1b/efeitos adversos , Lopinavir/efeitos adversos , Coronavírus da Síndrome Respiratória do Oriente Médio/patogenicidade , Estudos Multicêntricos como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Ritonavir/efeitos adversos , Arábia Saudita , Fatores de Tempo , Resultado do Tratamento
15.
J Neurol ; 267(2): 308-316, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30610426

RESUMO

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) with a diverse disease course involving inflammation and degeneration of neurons and axons. Multiple sclerosis results from a complex interaction of genetic and environmental factors and clinically several disease subtypes with marked variation in symptoms can be discerned. Disease-modifying therapies (DMTs) impact disease activity and outcome. Long-term follow-up studies of DMTs in MS have generally shown that the short-term effects in clinical trials are maintained for up to 21 years, e.g. in the case of interferon beta-1b. However, attainment can be a problem in these studies. On the one hand, so-called real-world studies can augment clinical trials by providing data on the long-term effectiveness and safety of DMTs but lack, on the other hand, randomization and may, in addition, also yield biased findings as a result of compliance issues. Long-term data from clinical trials in clinically isolated syndrome (CIS) patients have been limited but in the case of interferon beta-1b this aspect has been addressed over 11 years in the BENEFIT 11 trial. The results suggest that early treatment results in persistent long-term benefits including conversion to clinically definite MS (CDMS) as well as time to and risk of a first relapse. Here we primarily review the findings of the BENEFIT 11 trial in the context of long-term studies.


Assuntos
Esclerose Múltipla/terapia , Diagnóstico Precoce , Acetato de Glatiramer/uso terapêutico , Humanos , Interferon beta-1b/uso terapêutico , Resultado do Tratamento
16.
J Neuroimmunol ; 337: 577062, 2019 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-31521828

RESUMO

Interleukins (ILs)-22, 32α and 34 were monitored in the sera of relapsing-remitting multiple sclerosis (RRMS) patients at different time intervals with or without interferon ß-1b, interferon ß-1a and fingolimod treatments. The results showed that sera of untreated RRMS patients were statistically higher in concentration of IL-22 (P < .001), but not IL-32α and IL-34, than those of healthy individuals. Interestingly, interferon ß-1b, interferon ß-1a and fingolimod treatments led to a significant decrease of serum concentrations of ILs-22 and 32α, but not 34, at 6 and 12 months of treatment, compared to their initial concentrations before initiating therapy. The correlation analysis revealed that the changes of serum IL-22 (r = 0.814) and, to a lesser extent, IL-32α (r = 0.381) concentrations were positively correlated with those of expanded disability status score. In conclusion, serum IL-22 concentration may be a potential marker for MS disease severity and efficacy of treatment.


Assuntos
Cloridrato de Fingolimode/uso terapêutico , Interferon beta-1a/uso terapêutico , Interferon beta-1b/uso terapêutico , Interleucinas/sangue , Esclerose Múltipla Recidivante-Remitente/sangue , Adjuvantes Imunológicos/farmacologia , Adjuvantes Imunológicos/uso terapêutico , Adolescente , Adulto , Biomarcadores/sangue , Feminino , Cloridrato de Fingolimode/farmacologia , Humanos , Imunossupressores/farmacologia , Imunossupressores/uso terapêutico , Interferon beta-1a/farmacologia , Interferon beta-1b/farmacologia , Interleucinas/antagonistas & inibidores , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla Recidivante-Remitente/diagnóstico por imagem , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Distribuição Aleatória , Adulto Jovem
17.
Mult Scler Relat Disord ; 35: 119-127, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31374460

RESUMO

BACKGROUND: Disease-modifying therapy (DMT) for patients with relapsing-remitting multiple sclerosis (RRMS) have been shown to reduce relapses and new MRI lesions. However, few studies have assessed the impact of discontinuing DMT after a period of disease inactivity. OBJECTIVE: To investigate the impact of DMT discontinuation on clinical and radiological outcomes in RRMS patients. METHODS: 69 RRMS patients who discontinued DMT after a period of disease inactivity were identified from the Comprehensive Longitudinal Investigation of MS study at the Brigham and Women's Hospital, based on the following inclusion criteria: age 18 or older; treated with DMT ≥2 years; no clinical and radiological relapse ≥2 years until the discontinuation; not restarting DMT for ≥6 months after discontinuation. Patients matched by age, gender, treatment, treatment duration, disease duration and Expanded Disability Status Scale score who remained on DMT were identified. Univariate and multivariable Cox proportional hazard models with robust standard errors to account for the paired data were used to test the differences based on DMT discontinuation with the outcome measures: time to clinical relapse, MRI event, disability progression, and disease activity (either clinical relapse or MRI event). RESULTS: Based on the 69 pairs of patients, discontinuation was not associated with time to clinical relapse (HR = 0.87, 95% CI = 0.44-1.72, p = 0.69), MRI event (HR = 0.95, 95% CI = 0.57 to 1.59, p = 0.84), disability progression (HR = 1.24, 95% CI = 0.61 to 2.53, p = 0.55) and disease activity (HR = 0.89, 95% CI = 0.56 to 1.42, p = 0.62). When we performed subgroup analysis to compare the impact of DMT discontinuation between older (age > 45) and younger (age ≤ 45) patients, we found a significant difference in the association between young and old for time to MRI event (p = 0.012) and time to new disease activity (p = 0.0005). CONCLUSIONS: This study found that patients who discontinued treatment after a period of disease inactivity had a similar time to next event compared to subjects who remained on first-generation DMTs. In our cohort, we found that discontinuation after age 45 was associated with a stable disease course, while patients younger than age 45 who discontinued treatment were more likely to experience a new clinical relapse or MRI event.


Assuntos
Adjuvantes Imunológicos/uso terapêutico , Encéfalo/diagnóstico por imagem , Acetato de Glatiramer/uso terapêutico , Interferon beta-1b/uso terapêutico , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Medula Espinal/diagnóstico por imagem , Adulto , Progressão da Doença , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla Recidivante-Remitente/diagnóstico por imagem , Recidiva , Fatores de Tempo , Suspensão de Tratamento
18.
J Med Internet Res ; 21(7): e14373, 2019 07 29.
Artigo em Inglês | MEDLINE | ID: mdl-31359863

RESUMO

BACKGROUND: Accurate measurement of medication adherence using classical observational studies typically depends on patient self-reporting and is often costly and slow. In contrast, digital observational studies that collect data directly from the patient may pose minimal burden to patients while facilitating accurate, timely, and cost-efficient collection of real-world data. In Germany, ~80% of patients with multiple sclerosis (MS) treated with interferon beta 1b (Betaferon) use an electronic autoinjector (BETACONNECT), which automatically records every injection. Patients may also choose to use a medical app (myBETAapp) to document injection data and their well-being (using a "wellness tracker" feature). OBJECTIVE: The goal of this pilot study was to establish a digital study process that allows the collection of medication usage data and to assess medication usage among patients with MS treated with interferon beta-1b who use myBETAapp. METHODS: The PROmyBETAapp digital observational study was a mixed prospective and retrospective, noninterventional, cohort study conducted among users of myBETAapp in Germany (as of December 2017: registered accounts N=1334; actively used accounts N=522). Between September and December 2017, users received two invitations on their app asking them to participate. Interested patients were provided detailed information and completed an electronic consent process. Data from consenting patients' devices were collected retrospectively starting from the first day of usage if historical data were available in the database and collected prospectively following consent attainment. In total, 6 months of data on medication usage behavior were collected along with 3 months of wellness tracker data. Descriptive statistics were used to analyze persistence, compliance, and adherence to therapy. RESULTS: Of the 1334 registered accounts, 96 patients (7.2%) provided informed consent to participate in the study. Of these, one patient withdrew consent later. For another patient, injection data could not be recorded during the study period. Follow-up of the remaining 94 patients ended in May 2018. The mean age of participants was 46.6 years, and 50 (53%) were female. Over the 6-month study period, persistence with myBETAapp usage was 96% (90/94), mean compliance was 94% of injections completed, and adherence (persistence and ≥80% compliance) was 89% (84/94). There was no apparent difference between male and female participants and no trend across age groups. The wellness tracker was used by 21% of participants (20/94), with a mean of 3.1 entries per user. CONCLUSIONS: This study provides important information on medication usage among patients with MS treated with interferon beta-1b and on consenting behavior of patients in digital studies. In future studies, this approach may allow patients' feedback to be rapidly implemented in existing digital solutions. TRIAL REGISTRATION: ClinicalTrials.gov NCT03134573; https://clinicaltrials.gov/ct2/show/NCT03134573.


Assuntos
Interferon beta-1b/uso terapêutico , Adesão à Medicação/estatística & dados numéricos , Aplicativos Móveis/normas , Esclerose Múltipla/tratamento farmacológico , Estudos de Coortes , Feminino , Humanos , Interferon beta-1b/farmacologia , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/patologia , Projetos Piloto , Estudos Prospectivos , Estudos Retrospectivos
19.
Neuroimmunomodulation ; 26(6): 301-306, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31935737

RESUMO

INTRODUCTION: Multiple sclerosis (MS) is a neuroinflammatory autoimmune disease which involves the central nervous -system. Although the primary cause of MS is obscure, effects of some cytokine and chemokine patterns in both innate and adaptive immune systems have been described. -Objectives: Since limited studies have examined the role of interleukin (IL)-11 and chemokine CCL27 in MS, we aimed to identify changes in IL-11 and CCL27 gene expression and serum levels in relapsing-remitting MS (RRMS) patients, treated with interferon (IFN)-ß and glatiramer acetate (GA). METHODS: The serum level and gene expression of IL-11 and CCL27 were measured and compared between treatment-naïve MS patients and RRMS patients who were treated with high-dose IFN-ß1a, low-dose IFN-ß1a, IFN-ß1b, and GA via enzyme-linked immunosorbent assay (ELISA) and quantitative real-time polymerase chain reaction. RESULTS: A significant decrease was observed in the serum level of CCL27 in treatment-naïve patients and IFN-ß1b-treated patients compared to the healthy controls. On the other hand, a significant increase was found in the protein level of CCL27 in low-dose and high-dose IFN-ß1a groups compared to the treatment-naïve group. In addition, CCL27 gene expression was higher in patients treated with GA than in the treatment-naïve group. There were no significant changes in the gene expression or protein level of IL-11 in all experimental groups. Additionally, a positive correlation was found between IL-11 and CCL-27. CONCLUSION: Our results suggest the inflammatory role of CCL27 in MS patients, while IFN-ß1a seems to play a compensatory role for this chemokine.


Assuntos
Quimiocina CCL27/metabolismo , Acetato de Glatiramer/uso terapêutico , Imunossupressores/uso terapêutico , Interferon beta-1b/uso terapêutico , Interleucina-11/metabolismo , Esclerose Múltipla Recidivante-Remitente/imunologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico
20.
Lima; IETSI; 2019.
Não convencional em Espanhol | BRISA/RedTESA | ID: biblio-1010299

RESUMO

INTRODUCCIÓN: El presente dictamen expone la evaluación de la eficacia y seguridad de fingolimod, en comparación con interferón beta-1b, en pacientes adultos con esclerosis múltiple recurrente remitente muy activa, de evolución rápida. La esclerosis múltiple (EM) es una enfermedad inflamatoria y neurodegenerativa del sistema nervioso, caracterizada por episodios de disfunción neurológica, siendo variable el grado de recuperación. En general, la esperanza de vida de los pacientes con EM es menor que la de la población general en unos siete a 14 años. Existen diferentes formas de presentación de la enfermedad, siendo la EM con recaída-remisión (EMRR) la más frecuente de todos los tipos (85 % de pacientes con EM debutan con esta presentación). Dentro de los pacientes con EMRR, existe un subgrupo de pacientes con enfermedad severa de rápida evolución (EMRRSRE). Según la Agencia Europea de Medicamentos (EMA), la EMRRSRE es definida por la presencia de EM en pacientes con EMRR con dos o más brotes discapacitantes en un año, y con una o más lesiones realzadas con gadolinio en la resonancia magnética (RM) craneal o un incremento significativo de la carga lesional en T2 en comparación con una RM anterior. La definición de EMRRSRE no figura en las clasificaciones sobre EM revisadas ni en las guías de práctica clínica sobre la enfermedad. Este fenotipo de la EMRR (EMRRSRE) podría requerir de un abordaje terapéutico diferente para la prevención de la progresión del daño neurológico en el curso de la enfermedad. TECNOLOGÍA SANITARIA DE INTERÉS: Fingolimod (Gilenya®, Novartis) es un modulador del receptor de la esfingosina 1-fosfato, que, al ser metabolizado, da lugar al metabolito activo fingolimod fosfato. El metabolito en mención se une al receptor 1 de la esfingosina 1-fosfato de los linfocitos, atraviesa la barrera hematoencefálica y se une al receptor S1P1 localizado en las células neurales del sistema nervioso central. Su función como antagonista funcional del receptor S1P es bloquear la capacidad de los linfocitos de salir de los ganglios linfáticos, lo que produce una redistribución de los linfocitos sin disminución en su número. Este efecto resultaría en una reducción de la infiltración de células linfocíticas patógenas (incluyendo células proinflamatorias Th17) al SNC que producirían de otra forma inflamación y lesión del tejido nervioso. METODOLOGÍA: Se realizó una búsqueda sistemática de literatura con el objetivo de identificar evidencia sobre la eficacia y seguridad de fingolimod, comparado con interferón beta-1b, en pacientes adultos con EM recurrente remitente muy activa, de evolución rápida sin tratamiento previo. RESULTADOS: En la búsqueda de la evidencia hasta mayo de 2019, no se identificó algún estudio que responda directamente a la pregunta PICO donde se compare fingolimod con interferón beta-1b en la población de interés. Sin embargo, se logró identificar cinco documentos: dos guías de práctica clínica (GPC) elaboradas por la American Academy of Neurology (AAN) y European Committee of Treatment and Research in Multiple Sclerosis, European Academy of Neurology (ECTRIMS/EAN); dos evaluaciones de tecnologías sanitarias (ETS) realizadas por All Wales Medicines Strategy Group (AWMSG) y Scottish Medicines Consortium (SMC); y un único ensayo clínico aleatorizado (ECA) denominado TRANSFORMS que sirvieron como evidencia indirecta para ayudar a responder a la pregunta PICO de interés, puesto que no incluye de manera precisa a la población ni al comprador de interés. Así este ensayo incluye pacientes con EMRR, pero no específicamente pacientes con EMRRSRE y usa como comparador interferón beta-1a, en vez del interferón beta-1b. No obstante, la evidencia disponible (según el Dictamen preliminar de Evaluación de Tecnología Sanitaria N° 023-SDEPFyOTS-DETS-lETSl-2017) sugiere que interferón beta-1a sería útil para retrasar la progresión de la EMRR. Así, el ensayo TRANFORMS evaluó la eficacia y seguridad de fingolimod en comparación con interferón beta-1a en pacientes con EMRR. Este ensayo incluyó a una subpoblación de pacientes con EMRRSRE los cuales fueron evaluados en un análisis post hoc publicado por los autores del ensayo TRANSFORMS. No obstante, hay que tener cautela en la interpretación de los resultados obtenidos en el mencionado ensayo ya que este no fue diseñado para evaluar el uso de fingolimod en la población de interés (EMRRSRE) ni empleó el comparador de interés (interferón beta-1b). Por último, este ECA ha sido utilizado de igual forma como parte de la evidencia de las GPC y ETS incluidas en el presente dictamen. CONCLUSIONES: En el presente documento, se evaluó la mejor evidencia científica disponible hasta la actualidad sobre la eficacia y seguridad de fingolimod, en comparación con interferón beta-1b, en pacientes adultos con esclerosis múltiple recurrente remitente muy activa, de evolución rápida, sin tratamiento previo.  Las GPC de AAN y ECTRIMS/EAN no brindan recomendaciones específicas para la terapia de pacientes con EMRRSRE, siendo que ambos documentos señalan a interferón beta-1b y fingolimod como terapias modificadoras de la enfermedad útiles en pacientes con EMRR (es decir para una población más grande que la de interés). Ambas GPC utilizaron al estudio TRANSFORMS como evidencia. Sobre las ETS de SMC y AWMSG, ambas agencias recomiendan el empleo de fingolimod para pacientes con EMRRSRE. Las agencias reportan que no existieron diferencias estadísticamente significativas en la tasa de recaída anual ni un mejor perfil de seguridad, en cuanto a eventos adversos serios, del fingolimod comparados con los de interferón beta-1a para pacientes con EMRRSRE, con base en un análisis post hoc de tres ECAs. FREEDOMS, FREEDOMS II y TRANSFORMS. No obstante, la aprobación de uso de fingolimod dada por ambas agencias se condicionó a que los pacientes tengan acceso a un esquema de medicamentos que hagan costo efectivo su empleo. Este escenario no sería compatible con el sistema sanitario de EsSalud, por tratarse de diferentes contextos económicos y sanitarios. El estudio TRANSFORMS representa la mejor evidencia actualmente disponible para responder a la pregunta PICO establecida en el dictamen. Este es un ensayo clínico fase III, multicéntrico, aleatorizado, doble ciego, de grupos paralelos, que tuvo como objetivo comparar la eficacia y seguridad de fingolimod con la del interferón beta-1a. El estudio TRANSFORMS se incluyó como evidencia indirecta dado que el ensayo no fue desarrollado para evaluar la tecnología en la población de la pregunta PICO planteada para esta evaluación (EMRRSRE) sino en una población más grande (EMRR). Adicionalmente, si bien el estudio no emplea el comparador de interés (interferón beta-1b), algunos reportes encuentran que las tecnologías interferón beta-1a e interferón beta-1b serían comparables en su eficacia y seguridad en pacientes con EMRR, por lo que los resultados obtenidos en TRANSFORMS pueden tener utilidad para fines del presente dictamen. Por otro lado, cabe señalar que un análisis post hoc del estudio incluyó resultados para pacientes con EMRRSRE sin tratamiento previo. Si bien el estudio TRANSFORMS presentó como resultados una menor tasa de recaída anualizada en el grupo de fingolimod 0.5 mg para población con EMRR, para la población específica de interés (EMRRSRE) no se encontraron diferencias estadísticamente significativas en el análisis post hoc del estudio. Además, en el estudio TRANSFORMS se encontraron resultados inconsistentes en cuanto a los puntajes de discapacidad. Si bien se observó una mejora en el puntaje de la escala MSFC esta no se reflejó en los resultados con la EDSS. No obstante, a pesar de existir diferencias estadísticamente significativas con la escala MSFC, en el estudio no se estableció una mínima diferencia clínicamente relevante, lo que limita su interpretación. Adicionalmente, se observó una mayor tasa de eventos adversos serios y discontinuación debido a eventos adversos serios en el grupo de fingolimod, lo que indica que existe una mayor probabilidad de presentar eventos que comprometan la vida de los pacientes en este grupo respecto a los pacientes en terapia con interferón. El estudio no reportó resultados sobre calidad de vida. Entre las principales limitaciones del estudio se encuentran el corto seguimiento del estudio (12 meses), lo que genera incertidumbre sobre los resultados para la tasa de recaídas anualizada, y el no establecer puntos de corte para establecer la mínima diferencia clínicamente relevante para las escalas de discapacidad. De este modo, con la evidencia disponible, no es posible determinar el balance riesgo beneficio del empleo de fingolimod en comparación con interferón beta 1-b en la población de interés (pacientes con EMRRSRE sin tratamiento previo), más aún, fingolimod tendría un peor perfil de seguridad por eventos adversos serios en comparación con interferón. Cabe señalar que para la población general de pacientes con EMRR, las GPC recomiendan el uso de interferón beta-1a e interferón beta-1b, productos farmacéuticos actualmente disponibles en la institución. El Instituto de Evaluaciones de Tecnologías en Salud e Investigación - IETSI, no aprueba el uso de fingolimod en pacientes adultos con esclerosis múltiple recurrente remitente muy activa, de evolución rápida.


Assuntos
Humanos , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Cloridrato de Fingolimode/uso terapêutico , Interferon beta-1b/uso terapêutico , Avaliação da Tecnologia Biomédica , Análise Custo-Eficiência
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