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1.
Nutrients ; 13(7)2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34371920

RESUMO

Nutraceuticals, including vitamin D, vitamin A, zinc, lactoferrin, polyphenols coenzyme Q, magnesium, and selenium, are implicated in the modulation of the complex molecular pathways involved in the immune response against viral pathogens. A common element of the activity of nutraceuticals is their ability to enhance the innate immune response against pathogens by acting on the major cellular subsets and inducing the release of pro-inflammatory cytokines and antimicrobial peptides. In some cases, this action is accompanied by a direct antimicrobial effect, as evidenced in the specific case of lactoferrin. Furthermore, nutraceuticals act through complex molecular mechanisms to minimize the damage caused by the activation of the immune system against pathogens, reducing the oxidative damage, influencing the antigen presentation, enhancing the differentiation and proliferation of regulatory T cells, driving the differentiation of lymphocyte subsets, and modulating the production of pro-inflammatory cytokines. In this paper, we review the main molecular mechanisms responsible for the immunomodulatory function of nutraceuticals, focusing on the most relevant aspects for the prevention and treatment of viral infections.


Assuntos
Antivirais/uso terapêutico , Suplementos Nutricionais , Sistema Imunitário/efeitos dos fármacos , Fatores Imunológicos/uso terapêutico , Viroses/tratamento farmacológico , Vírus/efeitos dos fármacos , Animais , Antivirais/efeitos adversos , Suplementos Nutricionais/efeitos adversos , Interações Hospedeiro-Patógeno , Humanos , Sistema Imunitário/imunologia , Sistema Imunitário/metabolismo , Sistema Imunitário/virologia , Fatores Imunológicos/efeitos adversos , Resultado do Tratamento , Viroses/imunologia , Viroses/metabolismo , Viroses/virologia , Vírus/imunologia , Vírus/patogenicidade
2.
Artigo em Inglês | MEDLINE | ID: mdl-34341094

RESUMO

BACKGROUND AND OBJECTIVES: We sought to define the risk of severe coronavirus disease 2019 (COVID-19) infection requiring hospitalization in patients with CNS demyelinating diseases such as MS and the factors that increase the risk for severe infection to guide decisions regarding patient care during the COVID-19 pandemic. METHODS: A pilot cohort of 91 patients with confirmed or suspected COVID-19 infection from the Northeastern United States was analyzed to characterize patient risk factors and factors associated with an increased severity of COVID-19 infection. Univariate analysis of variance was performed using the Mann-Whitney U test or analysis of variance for continuous variables and the χ2 or Fisher exact test for nominal variables. Univariate and stepwise multivariate logistic regression identified clinical characteristics or symptoms associated with hospitalization. RESULTS: Our cohort demonstrated a 27.5% hospitalization rate and a 4.4% case fatality rate. Performance on Timed 25-Foot Walk before COVID-19 infection, age, number of comorbidities, and presenting symptoms of nausea/vomiting and neurologic symptoms (e.g., paresthesia or weakness) were independent risk factors for hospitalization, whereas headache predicted a milder course without hospitalization. An absolute lymphocyte count was lower in hospitalized patients during COVID-19 infection. Use of disease-modifying therapy did not increase the risk of hospitalization but was associated with an increased need for respiratory support. DISCUSSION: The case fatality and hospitalization rates in our cohort were similar to those found in MS and general population COVID-19 cohorts within the region. Hospitalization was associated with increased disability, age, and comorbidities but not disease-modifying therapy use.


Assuntos
COVID-19 , Doenças Autoimunes Desmielinizantes do Sistema Nervoso Central , Hospitalização/estatística & dados numéricos , Fatores Imunológicos/uso terapêutico , Sistema de Registros/estatística & dados numéricos , Respiração Artificial/estatística & dados numéricos , Adulto , COVID-19/diagnóstico , COVID-19/epidemiologia , COVID-19/terapia , Estudos de Coortes , Comorbidade , Doenças Autoimunes Desmielinizantes do Sistema Nervoso Central/tratamento farmacológico , Doenças Autoimunes Desmielinizantes do Sistema Nervoso Central/epidemiologia , Feminino , Humanos , Fatores Imunológicos/efeitos adversos , Masculino , Pessoa de Meia-Idade , Mortalidade , New England/epidemiologia , Projetos Piloto , Fatores de Risco , Índice de Gravidade de Doença
3.
N Engl J Med ; 385(3): 228-238, 2021 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-34260836

RESUMO

BACKGROUND: Chronic graft-versus-host disease (GVHD), a major complication of allogeneic stem-cell transplantation, becomes glucocorticoid-refractory or glucocorticoid-dependent in approximately 50% of patients. Robust data from phase 3 randomized studies evaluating second-line therapy for chronic GVHD are lacking. In retrospective surveys, ruxolitinib, a Janus kinase (JAK1-JAK2) inhibitor, showed potential efficacy in patients with glucocorticoid-refractory or -dependent chronic GVHD. METHODS: This phase 3 open-label, randomized trial evaluated the efficacy and safety of ruxolitinib at a dose of 10 mg twice daily, as compared with the investigator's choice of therapy from a list of 10 commonly used options considered best available care (control), in patients 12 years of age or older with moderate or severe glucocorticoid-refractory or -dependent chronic GVHD. The primary end point was overall response (complete or partial response) at week 24; key secondary end points were failure-free survival and improved score on the modified Lee Symptom Scale at week 24. RESULTS: A total of 329 patients underwent randomization; 165 patients were assigned to receive ruxolitinib and 164 patients to receive control therapy. Overall response at week 24 was greater in the ruxolitinib group than in the control group (49.7% vs. 25.6%; odds ratio, 2.99; P<0.001). Ruxolitinib led to longer median failure-free survival than control (>18.6 months vs. 5.7 months; hazard ratio, 0.37; P<0.001) and higher symptom response (24.2% vs. 11.0%; odds ratio, 2.62; P = 0.001). The most common (occurring in ≥10% patients) adverse events of grade 3 or higher up to week 24 were thrombocytopenia (15.2% in the ruxolitinib group and 10.1% in the control group) and anemia (12.7% and 7.6%, respectively). The incidence of cytomegalovirus infections and reactivations was similar in the two groups. CONCLUSIONS: Among patients with glucocorticoid-refractory or -dependent chronic GVHD, ruxolitinib led to significantly greater overall response, failure-free survival, and symptom response. The incidence of thrombocytopenia and anemia was greater with ruxolitinib. (Funded by Novartis and Incyte; REACH3 ClinicalTrials.gov number, NCT03112603.).


Assuntos
Doença Enxerto-Hospedeiro/tratamento farmacológico , Fatores Imunológicos/uso terapêutico , Janus Quinases/antagonistas & inibidores , Pirazóis/uso terapêutico , Adolescente , Adulto , Idoso , Criança , Infecções por Citomegalovirus/etiologia , Feminino , Glucocorticoides/uso terapêutico , Humanos , Fatores Imunológicos/efeitos adversos , Masculino , Pessoa de Meia-Idade , Fotoferese , Pirazóis/efeitos adversos , Análise de Sobrevida , Trombocitopenia/induzido quimicamente , Falha de Tratamento , Adulto Jovem
4.
J Autoimmun ; 123: 102687, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34311142

RESUMO

The impact of SARS-CoV-2 infection in patients with autoimmune/auto-inflammatory rheumatic diseases (AARD) under immunomodulatory treatment has been a focus of interest during the COVID-19 pandemic. In this observational study, demographic data, disease related features and comorbidities, COVID-19 manifestations and outcome as well as antibody responses to SARS-CoV-2 were recorded among 77 consecutive patients with underlying AARD infected by SARS-CoV-2. Analysis of data was performed using univariate and multivariate models. Most patients (68.8%) had a mild COVID-19 course. The predominant clinical manifestations were fatigue (58.4%), low grade fever (45.4%) and upper respiratory tract symptoms (68.8%). About a quarter of patients required hospitalization (23.3%) and the mortality rate was 1.3%. Regarding COVID-19 severity, prior treatment with corticosteroids, mycophenolate mofetil or rituximab was more common in patients who developed a more serious disease course (60.0 vs 29.9%, p = 0.003, 40.0 vs 7.5%, p = 0.003, 10.0 vs 0.0%, p = 0.009, respectively). When disease related features and comorbidities were considered in multivariate models, older age and lung disease in the context of the AARD were found to be independent predictive factors for hospitalization (OR [95%]: 1.09 [1.03-1.15] and 6.43 [1.11-37.19]). Among COVID-19 related features, patients with shortness of breath and high-grade fever were more likely to get hospitalized (OR [95%]: 7.06 [1.36-36.57], 12.04 [2.96-48.86]), while anosmia was independently associated with lower hospitalization risk (OR [95%]: 0.09 [0.01-0.99]). Though the majority of AARD patients displayed a mild COVID-19 course, certain underlying disease features and COVID-19 related manifestations should prompt alertness for the physician to identify patients with AARD at high risk for severe COVID-19 and need for hospitalization.


Assuntos
Doenças Autoimunes/epidemiologia , COVID-19/epidemiologia , Doenças do Tecido Conjuntivo/epidemiologia , SARS-CoV-2 , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antivirais/biossíntese , Infecções Assintomáticas/epidemiologia , Doenças Autoimunes/tratamento farmacológico , Doenças Autoimunes/imunologia , Comorbidade , Doenças do Tecido Conjuntivo/tratamento farmacológico , Doenças do Tecido Conjuntivo/imunologia , Estado Terminal , Feminino , Grécia/epidemiologia , Hospitalização/estatística & dados numéricos , Humanos , Hipotireoidismo/epidemiologia , Hospedeiro Imunocomprometido , Imunoglobulina G/biossíntese , Fatores Imunológicos/efeitos adversos , Fatores Imunológicos/uso terapêutico , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Inflamação , Pneumopatias/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Observacionais como Assunto , Literatura de Revisão como Assunto , Doenças Reumáticas/tratamento farmacológico , Doenças Reumáticas/epidemiologia , SARS-CoV-2/imunologia , Índice de Gravidade de Doença , Avaliação de Sintomas
5.
Aliment Pharmacol Ther ; 54(6): 814-832, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34247410

RESUMO

BACKGROUND: With the advent of biological therapy in IBD, it is uncertain to what extent 5aminosalicylates (5ASA) are used. AIMS: To explore whether or not 5ASA is continued once biological or immunomodulator therapy is initiated, and the outcomes in those who continued the 5ASAs. METHODS: We conducted a retrospective cohort study using the population-based University of Manitoba IBD Epidemiologic Database which includes prescription drug dispensation from 1996 through 2018. We assessed outcomes among 5ASA users who continued versus discontinued 5ASA after initiation of anti-TNF therapy or immunomodulators. RESULTS: In all, 8379 (77%) of persons with IBD received at least one 5ASA dispensation (85% of ulcerative colitis, UC and 68% of Crohn's disease, CD). There was a reduction in later years, particularly for CD. The most common pattern of 5ASA use was intermittent at 65.1% (stopping and restarting use) versus one-time (4.1%), previous continuous (13.8%) and persistent (17%). Among the total IBD population use was 59% oral, 3% rectal and 14% combination. Of all 5ASA starts, only 25% were continued longer than 20 months. After immunomodulator or anti-TNF initiation, there was no difference in either UC or CD for negative outcomes (hospitalisation, surgery, corticosteroid starts, colorectal cancers or drug-related adverse events) between those who continued 5ASA versus those who discontinued. CONCLUSIONS: 5ASA remains commonly prescribed in UC and CD. Rates of persistent use in UC are low. Once an anti-TNF or immunomodulator is initiated, continuation of 5ASA seems to add no benefit.


Assuntos
Colite Ulcerativa , Doença de Crohn , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/epidemiologia , Humanos , Fatores Imunológicos/efeitos adversos , Estudos Retrospectivos , Inibidores do Fator de Necrose Tumoral
7.
Ann Clin Transl Neurol ; 8(8): 1738-1744, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34240579

RESUMO

We evaluated the effect of DMTs on Covid-19 severity in patients with MS, with a pooled-analysis of two large cohorts from Italy and France. The association of baseline characteristics and DMTs with Covid-19 severity was assessed by multivariate ordinal-logistic models and pooled by a fixed-effect meta-analysis. 1066 patients with MS from Italy and 721 from France were included. In the multivariate model, anti-CD20 therapies were significantly associated (OR = 2.05, 95%CI = 1.39-3.02, p < 0.001) with Covid-19 severity, whereas interferon indicated a decreased risk (OR = 0.42, 95%CI = 0.18-0.99, p = 0.047). This pooled-analysis confirms an increased risk of severe Covid-19 in patients on anti-CD20 therapies and supports the protective role of interferon.


Assuntos
Anticorpos Monoclonais Humanizados/farmacologia , COVID-19/fisiopatologia , Fatores Imunológicos/farmacologia , Interferons/farmacologia , Esclerose Múltipla/tratamento farmacológico , Rituximab/farmacologia , Adulto , Anticorpos Monoclonais Humanizados/efeitos adversos , COVID-19/epidemiologia , Feminino , França/epidemiologia , Humanos , Fatores Imunológicos/efeitos adversos , Interferons/efeitos adversos , Itália/epidemiologia , Masculino , Metanálise como Assunto , Pessoa de Meia-Idade , Esclerose Múltipla/epidemiologia , Análise Multivariada , Fatores de Proteção , Estudos Retrospectivos , Fatores de Risco , Rituximab/efeitos adversos , Índice de Gravidade de Doença
10.
Med Clin North Am ; 105(4): 627-641, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34059242

RESUMO

Psoriasis is a systemic inflammatory condition that negatively affects the quality of life and medical health of 125 million individuals globally. Although psoriasis has historically been viewed as a skin-limited disease and managed with topical agents (eg, coal tar, corticosteroids, and vitamin D analogues), the recontextualization of psoriasis as a systemic condition involving multiple organ systems has prompted the development of numerous immunomodulating, systemic agents with more targeted mechanisms of action. This article briefly discusses the indications and nuances of new and developing therapeutic agents for psoriasis management.


Assuntos
Interleucinas/antagonistas & inibidores , Psoríase/patologia , Psoríase/terapia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Administração Tópica , Corticosteroides/administração & dosagem , Corticosteroides/uso terapêutico , Ensaios Clínicos como Assunto , Alcatrão/administração & dosagem , Alcatrão/uso terapêutico , Inibidores Enzimáticos/uso terapêutico , Humanos , Fatores Imunológicos/efeitos adversos , Fatores Imunológicos/uso terapêutico , Inibidores de Janus Quinases/uso terapêutico , Psoríase/diagnóstico , Psoríase/psicologia , Pirazóis/uso terapêutico , Pirimidinas/uso terapêutico , Qualidade de Vida/psicologia , Receptores de Hidrocarboneto Arílico , Vitamina D/administração & dosagem , Vitamina D/análogos & derivados , Vitamina D/uso terapêutico
11.
Adv Ther ; 38(7): 3724-3742, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34014549

RESUMO

INTRODUCTION: STRIVE was a 4-year, multicenter, observational, open-label, single-arm study of natalizumab treatment in anti-JC virus antibody-negative (JCV-negative) relapsing-remitting multiple sclerosis (RRMS) patients with disease duration ≤ 3 years. The objective of STRIVE was to examine no evidence of disease activity (NEDA) status and predictors of NEDA in natalizumab-treated patients with early RRMS. METHODS: Proportions of patients with NEDA were evaluated along with baseline predictors of NEDA, annualized relapse rate, 24-week confirmed disability worsening (CDW), magnetic resonance imaging assessments (T2 and gadolinium-enhancing lesions), and serious adverse events. RESULTS: In years 1 and 2, 56.1% (95% confidence interval [CI] 48.7-63.4%) and 73.6% (95% CI 66.2-80.2%) of patients (intent-to-treat population [N = 222]), respectively, achieved NEDA. In years 3 and 4, 84.6% (95% CI 78.0-89.9%) and 91.9% (95% CI 86.4-95.8%) of patients, respectively, achieved Clinical NEDA (no relapses or 24-week CDW). Baseline predictors of NEDA in year 4 were Expanded Disability Status Scale score ≤ 2.0 (odds ratio [OR] = 3.85 [95% CI 1.54-9.63]; p = 0.004) and T2 lesion volume > 4 cc (OR = 0.39 [95% CI 0.15-0.98]; p = 0.046), with the latter also predicting Clinical NEDA in year 4 (OR = 0.21 [95% CI 0.05-0.92]; p = 0.038). The cumulative probability of CDW at year 4 was 19.3%. Serious adverse events were reported in 11.3% of patients. CONCLUSION: These results support the long-term safety and effectiveness of natalizumab. Baseline predictors of NEDA help to inform benefit-risk assessments of natalizumab treatment in JCV-negative patients with early RRMS. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT01485003.


Assuntos
Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Humanos , Fatores Imunológicos/efeitos adversos , Imageamento por Ressonância Magnética , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Natalizumab/efeitos adversos , Resultado do Tratamento
12.
BMC Neurol ; 21(1): 183, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33933026

RESUMO

BACKGROUND: Choosing a safe disease modifying therapy during the COVID-19 pandemic is challenging. This case series study was conducted to determine the incidence rate and the course of Covid-19 infection in MS/NMOSD patients treated with Rituximab. METHODS: In this study, we designed a web-based questionnaire. Baseline information such as patient- reported walking disability, total number of Rituximab infusions received, delayed injections, occurrence of any relapse, and the use of corticosteroids during the pandemic were collected. Also, information regarding the Covid-19 pandemic such as adherence to self-isolation, any recent exposure to an infected individual and the presence of suggestive symptoms were collected. In case of positive test results, patients were grouped into 2 categories; mild to moderate and seriously ill and outcomes were evaluated as favorable (improved/ discharged) and unfavorable (expired). RESULTS: Two hundred fifty-eight patients with Multiple Sclerosis were enrolled in this study, 9 of the subjects (3.4%) were confirmed positive for Covid-19, five of which required hospitalizations (55.5%), two patients required ICU admission (22.2%) and 2 two patients died (22.2%). None of these patients ever mentioned using corticosteroids during the pandemic. In comparison to MS patients who were not receiving disease modifying therapy (DMT), our study indicated a higher incidence of Covid-19 infection, higher ratio of serious illness and a higher fatality ratio. CONCLUSIONS: Rituximab seems not to be safe enough during the pandemic.


Assuntos
COVID-19/epidemiologia , Fatores Imunológicos/efeitos adversos , Esclerose Múltipla/epidemiologia , Rituximab/efeitos adversos , Adolescente , Adulto , Feminino , Humanos , Fatores Imunológicos/administração & dosagem , Masculino , Recidiva , Rituximab/administração & dosagem , Adulto Jovem
14.
Curr Opin Anaesthesiol ; 34(3): 357-363, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33935185

RESUMO

PURPOSE OF REVIEW: Anesthetics are known to have immunomodulatory effects. These can be detrimental, inducing immunosuppression and facilitating the development of opportunistic infections, especially when used at high doses, for prolonged periods, or in patients with preexisting immune deficiency; or beneficial, modulating the inflammatory response, particularly in critical illness and systemic hyperinflammatory states. RECENT FINDINGS: Anesthetics can have microbicidal properties, and both anti- and pro-inflammatory effects. They can act directly on immune cells as well as modulate immunity through indirect pathways, acting on the neuroimmune stress response, and have recently been described to interact with the gut microbiota. SUMMARY: Anesthesiologists should take into consideration the immunomodulatory properties of anesthetic agents in addition to their hemodynamic, neuroprotective, and other impacts. In future, patient stratification according to the perioperative assessment of serum biomarkers associated with postoperative complications may be used to guide anesthetic agent selection based on their immunomodulatory properties.


Assuntos
Anestesia , Anestésicos , Anestesia/efeitos adversos , Anestésicos/efeitos adversos , Humanos , Fatores Imunológicos/efeitos adversos , Complicações Pós-Operatórias
15.
J Neurovirol ; 27(3): 510-513, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33876412

RESUMO

Progressive multifocal leucoencephalopathy is a serious side effect of natalizumab, a humanized monoclonal antibody approved for the treatment of multiple sclerosis. Here, we report a case of unexpected worsening of natalizumab-related progressive multifocal leucoencephalopathy following COVID-19. After natalizumab discontinuation, a slight neurological improvement was observed, but, two months later the patient was admitted to the hospital because of neurological deterioration and COVID-19 mild pneumonia. Except for SARS-CoV-2 infection, no other potential factors of neurological worsening were identified. Thus, we pose the hypothesis that SARS-CoV-2 was instrumental in the progressive multifocal leucoencephalopathy deterioration.


Assuntos
COVID-19/complicações , Leucoencefalopatia Multifocal Progressiva/induzido quimicamente , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Natalizumab/efeitos adversos , Humanos , Fatores Imunológicos/efeitos adversos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla Recidivante-Remitente/complicações , Pneumonia/virologia , SARS-CoV-2
16.
Drug Des Devel Ther ; 15: 1345-1356, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33824579

RESUMO

The coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), continues to spread around the world. While prophylactic vaccines against SARS-CoV-2 are making great progress, there is still a need to explore safe and effective therapies with biological products for COVID-19. Currently clinical trial efforts are planned and ongoing using different biological agents for anti-inflammatory therapies, immunomodulation, and therapeutic repair in COVID-19. Targeting inflammatory cytokines with antibodies or inhibitors may be an urgent therapeutic strategy for COVID-19. Importantly, it is critical for an in-depth understanding of these new clinical therapeutic agents in their conditions that are probably involved in both physiological and pathological host responses. In this article, we analyze the potential implications for the current clinical trials of therapeutic biologics and address issues for the development of the COVID-19-related biological therapies.


Assuntos
Anti-Inflamatórios/uso terapêutico , Produtos Biológicos/uso terapêutico , COVID-19/tratamento farmacológico , Citocinas/antagonistas & inibidores , Fatores Imunológicos/uso terapêutico , SARS-CoV-2/imunologia , Anti-Inflamatórios/efeitos adversos , Produtos Biológicos/efeitos adversos , COVID-19/diagnóstico , COVID-19/imunologia , COVID-19/virologia , Ensaios Clínicos como Assunto , Citocinas/imunologia , Interações Hospedeiro-Patógeno , Humanos , Fatores Imunológicos/efeitos adversos , Terapia de Alvo Molecular , SARS-CoV-2/patogenicidade , Resultado do Tratamento
18.
Expert Opin Drug Saf ; 20(6): 735-740, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33641547

RESUMO

Introduction: Considering the need for effective postmarketing surveillance of disease-modifying therapies (DMTs) in multiple sclerosis (MS), we analyzed the potential of the spontaneous reports for safety signal detection, verifying the completeness of the reports in the FDA Adverse Event Reporting System (FAERS).Methods: All reports with DMTs for MS considered the primary suspect cause of ADRs and registered between January 2004 and June 2019 were selected. The vigiGrade completeness score was applied and reports with a score greater than 0.80 were considered well documented. Descriptive statistical analysis and comparisons of well-documented reports by DMTs were performed.Results: A total of 297,926 reports were analyzed. The lowest completeness rates were observed for type of report (13.5%), dose (62.7%), and time from treatment start to the ADR (79.0%). Overall, 80.8% of reports were classified as well documented and those related to natalizumab had the highest proportion (92.4%, p < 0.001), while the lowest was observed for reports sent in 2017 (53.1%, p < 0.001) and for teriflunomide (48.5%, p < 0.001).Conclusions: The high proportion of well-documented reports for DMTs indicates that they can be a valuable source for safety signal detection. A more careful analysis should be performed for data from the groups identified with low completeness to avoid the disclosure of spurious results.


Assuntos
Sistemas de Notificação de Reações Adversas a Medicamentos/estatística & dados numéricos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Esclerose Múltipla/tratamento farmacológico , Vigilância de Produtos Comercializados/estatística & dados numéricos , Sistemas de Notificação de Reações Adversas a Medicamentos/normas , Humanos , Fatores Imunológicos/administração & dosagem , Fatores Imunológicos/efeitos adversos , Farmacovigilância , Vigilância de Produtos Comercializados/normas , Estados Unidos , United States Food and Drug Administration
19.
Mult Scler Relat Disord ; 51: 102865, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33714125

RESUMO

BACKGROUND: A significant proportion of pediatric-onset multiple sclerosis (POMS) patients do not respond to first-line disease-modifying therapies. Clinical trials showed that natalizumab is effective and safe in adults, but there are limited clinical trial data for children. Natalizumab is currently prescribed off-label for POMS. We aimed to characterize the effectiveness, safety and tolerability of natalizumab in all POMS cases treated in Portugal (from 2007 to 2018). METHODS: Data from clinical records were retrospectively collected for all POMS cases treated with natalizumab in Portugal. RESULTS: Twenty-one patients were included, 14 (67%) of which were female. The median age at POMS diagnosis was 13 years old. The median duration of treatment with natalizumab was 2 years and 3 months. Median Expanded Disability Status Scale score decreased from 1.5 to 1.0 after 24 months. The Annualized Relapse Rate decreased from 1.31 events/patient/year before treatment with natalizumab to 0 after 12 months of treatment and to 0.04 after 24 months. No gadolinium-enhancing lesions or new or enlarged T2 hyperintense lesions were observed in 8/8 patients (100%) after 12 months, and 4/5 (80%) after 24 months. There was one possible serious adverse event, which did not require dose adjustment. Five patients discontinued treatment due to positive anti-JCV (JC virus) antibody JC serostatus. CONCLUSION: Natalizumab may be an effective and safe disease-modifying therapy for POMS. Our results are in line with data published for the adult population, as well as with similar observational studies in pediatric populations in other regions.


Assuntos
Vírus JC , Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Adolescente , Adulto , Criança , Feminino , Humanos , Fatores Imunológicos/efeitos adversos , Esclerose Múltipla/tratamento farmacológico , Natalizumab/efeitos adversos , Portugal , Estudos Retrospectivos
20.
Intern Med ; 60(18): 2985-2989, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-33776000

RESUMO

There are an increasing number of reports on the safe use of rituximab (RTX), a chimeric anti-CD20 monoclonal antibody, in pregnant women with hematological malignancies or refractory autoimmune diseases. In 2014, the use of RTX for patients with complicated steroid-dependent nephrotic syndrome (SDNS) was approved in Japan. We herein report a woman with childhood-onset complicated SDNS due to focal and segmental glomerulosclerosis, who had two successful pregnancies while receiving RTX maintenance therapy. No adverse complications were observed during the pregnancies, and she delivered healthy newborns. This case suggested that RTX may be used safely in pregnant women complicated with SDNS.


Assuntos
Glomerulosclerose Segmentar e Focal , Síndrome Nefrótica , Criança , Feminino , Humanos , Fatores Imunológicos/efeitos adversos , Imunossupressores , Recém-Nascido , Japão , Síndrome Nefrótica/tratamento farmacológico , Gravidez , Rituximab/efeitos adversos , Esteroides , Resultado do Tratamento
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