Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 6.752
Filtrar
1.
Pan Afr Med J ; 35(Suppl 2): 134, 2020.
Artigo em Francês | MEDLINE | ID: mdl-33193949

RESUMO

Hydroxychloroquine is an agent used as a treatment but also considered as a prophylaxis for SARS-CoV-2 infection. We report the case of a patient who developed COVID-19 while on hydroxychloroquine for mixed connectivitis associated with spondyloarthritis. Although more work is needed before any conclusions can be drawn, this raises questions about the protective role of this drug against infection. Are they really protected against COVID-19 or will they develop pauci-symptomatic forms?


Assuntos
Antirreumáticos/uso terapêutico , Antivirais/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Etanercepte/uso terapêutico , Hidroxicloroquina/uso terapêutico , Doença Mista do Tecido Conjuntivo/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Dermatopatias Virais/etiologia , Espondiloartropatias/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Urticária/etiologia , Antirreumáticos/efeitos adversos , Infecções por Coronavirus/complicações , Suscetibilidade a Doenças , Etanercepte/efeitos adversos , Humanos , Masculino , Doença Mista do Tecido Conjuntivo/complicações , Pandemias , Pneumonia Viral/complicações , Espondiloartropatias/complicações , Fator de Necrose Tumoral alfa/efeitos adversos , Adulto Jovem
2.
N Engl J Med ; 383(16): 1511-1521, 2020 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-33053283

RESUMO

BACKGROUND: Upadacitinib is an oral selective Janus kinase inhibitor to treat rheumatoid arthritis. The efficacy and safety of upadacitinib as compared with abatacept, a T-cell costimulation modulator, in patients with rheumatoid arthritis refractory to biologic disease-modifying antirheumatic drugs (DMARDs) are unclear. METHODS: In this 24-week, phase 3, double-blind, controlled trial, we randomly assigned patients in a 1:1 ratio to receive oral upadacitinib (15 mg once daily) or intravenous abatacept, each in combination with stable synthetic DMARDs. The primary end point was the change from baseline in the composite Disease Activity Score for 28 joints based on the C-reactive protein level (DAS28-CRP; range, 0 to 9.4, with higher scores indicating more disease activity) at week 12, assessed for noninferiority. Key secondary end points at week 12 were the superiority of upadacitinib over abatacept in the change from baseline in the DAS28-CRP and the percentage of patients having clinical remission according to a DAS28-CRP of less than 2.6. RESULTS: A total of 303 patients received upadacitinib, and 309 patients received abatacept. From baseline DAS28-CRP values of 5.70 in the upadacitinib group and 5.88 in the abatacept group, the mean change at week 12 was -2.52 and -2.00, respectively (difference, -0.52 points; 95% confidence interval [CI], -0.69 to -0.35; P<0.001 for noninferiority; P<0.001 for superiority). The percentage of patients having remission was 30.0% with upadacitinib and 13.3% with abatacept (difference, 16.8 percentage points; 95% CI, 10.4 to 23.2; P<0.001 for superiority). During the treatment period, one death, one nonfatal stroke, and two venous thromboembolic events occurred in the upadacitinib group, and more patients in the upadacitinib group than in the abatacept group had elevated hepatic aminotransferase levels. CONCLUSIONS: In patients with rheumatoid arthritis refractory to biologic DMARDs, upadacitinib was superior to abatacept in the change from baseline in the DAS28-CRP and the achievement of remission at week 12 but was associated with more serious adverse events. Longer and larger trials are required in order to determine the effect and safety of upadacitinib in patients with rheumatoid arthritis. (Funded by AbbVie; SELECT-CHOICE Clinicaltrials.gov number, NCT03086343.).


Assuntos
Abatacepte/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Proteína Coestimuladora de Linfócitos T Induzíveis/antagonistas & inibidores , Inibidores de Janus Quinases/uso terapêutico , Abatacepte/efeitos adversos , Administração Oral , Antirreumáticos/efeitos adversos , Artrite Reumatoide/sangue , Proteína C-Reativa/análise , Método Duplo-Cego , Tolerância a Medicamentos , Feminino , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Humanos , Infusões Intravenosas , Análise de Intenção de Tratamento , Inibidores de Janus Quinases/efeitos adversos , Masculino , Pessoa de Meia-Idade , Indução de Remissão
4.
Isr Med Assoc J ; 9(22): 491-497, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32954695

RESUMO

BACKGROUND: Tocilizumab is an interleukin 6 (IL-6) receptor antagonist used treat moderate to severe active rheumatoid arthritis (RA). Both intravenous (IV) and subcutaneous (SC) routes are approved for the treatment of adults with RA. OBJECTIVES: To evaluate SC tocilizumab in a real-life clinical setting. METHODS: Our study was a multi-center, open-label, single-arm study. Participants were adults with a diagnosis of active RA, previously treated with disease-modifying antirheumatic drugs (DMARDs), with or without biologic agents. Participants received a weekly SC injection of tocilizumab 162 mg as monotherapy or in combination with methotrexate or DMARDs for 24 weeks. Efficacy, safety, and immunogenicity were assessed. RESULTS: Treatment of 100 patients over 24 weeks resulted in improvement in all efficacy parameters assessed: Clinical Disease Activity Index, Disease Activity Score using 28 joint counts and erythrocyte sedimentation rate, American College of Rheumatology response scores, Simplified Disease Activity Index, tender and swollen joint counts, and patient-reported outcomes including fatigue, global assessment of disease activity, pain, and Health Assessment Quality of Life Disease Index. Improvement was achieved as early as the second week of treatment. There were 473 adverse events (AEs)/100 patient-years (PY) and 16.66 serious AEs/100 PY. The most common AEs were neutropenia (12%), leukopenia (11%), and increased hepatic enzymes (11%). Of a total of 42 PY, the rates of serious infections and AEs leading to discontinuation were 4.8, and 11.9 events/100 PY, respectively. CONCLUSIONS: The safety, tolerability, and efficacy profile of tocilizumab SC were comparable to those reported in other studies evaluating the IV and SC routes of administration.


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Antirreumáticos/administração & dosagem , Artrite Reumatoide/tratamento farmacológico , Qualidade de Vida , Adulto , Idoso , Anticorpos Monoclonais Humanizados/efeitos adversos , Antirreumáticos/efeitos adversos , Artrite Reumatoide/fisiopatologia , Quimioterapia Combinada , Feminino , Humanos , Injeções Subcutâneas , Masculino , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Resultado do Tratamento
5.
PLoS Med ; 17(9): e1003296, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32960885

RESUMO

BACKGROUND: Based on different genetic and environmental risk factors and histology, it has been proposed that rheumatoid arthritis (RA) consists of 2 types: autoantibody-positive and autoantibody-negative RA. However, until now, this remained hypothetical. To assess this hypothesis, we studied whether the long-term outcomes differed for these 2 groups of RA patients. METHODS AND FINDINGS: In the Leiden Early Arthritis Clinic cohort, 1,285 consecutive RA patients were included between 1993 and 2016 and followed yearly. Treatment protocols in routine care improved over time, irrespective of autoantibody status, and 5 inclusion periods were used as instrumental variables: 1993-1996, delayed mild disease-modifying antirheumatic drug (DMARD) initiation (reference period); 1997-2000, early mild DMARDs; 2001-2005, early methotrexate; 2006-2010, early methotrexate followed by treat-to-target adjustments; 2011-2016, similar to 2006-2010 plus additional efforts for very early referral. Three long-term outcomes were studied: sustained DMARD-free remission (SDFR) (persistent absence of clinical synovitis after DMARD cessation), mortality, and functional disability measured by yearly Health Assessment Questionnaire (HAQ). Treatment response in the short term (disease activity) was measured by Disease Activity Score-28 with erythrocyte sedimentation rate (DAS28-ESR). Linear mixed models and Cox regression were used, stratified for autoantibody positivity, defined as IgG anti-CCP2 and/or IgM rheumatoid factor positivity. In total, 823 patients had autoantibody-positive RA (mean age 55 years, 67% female); 462 patients had autoantibody-negative RA (age 60 years, 64% female). Age, gender, and percentage of autoantibody-positive patients were stable throughout the inclusion periods. Disease activity significantly decreased over time within both groups. SDFR rates increased after introduction of treat-to-target (hazard ratio [HR] 2006-2010 relative to 1993-1996: 3.35 [95% CI 1.46 to 7.72; p = 0.004]; HR 2011-2016: 4.57 [95% CI 1.80 to 11.6; p = 0.001]) in autoantibody-positive RA, but not in autoantibody-negative RA. In autoantibody-positive RA, mortality decreased significantly after the introduction of treat-to-target treatment adjustments (HR 2006-2010: 0.56 [95% CI 0.34 to 0.92; p = 0.023]; HR 2011-2016: 0.33 [95% CI 0.14 to 0.77; p = 0.010]), but not in autoantibody-negative RA (HR 2006-2010: 0.79 [95% CI 0.40 to 1.56; p = 0.50]; HR 2011-2016: 0.36 [95% CI 0.10 to 1.34; p = 0.13]). Similarly, functional disability improved in autoantibody-positive RA for the periods after 2000 relative to 1993-1996 (range -0.16 [95% CI -0.29 to -0.03; p = 0.043] to -0.32 [95% CI -0.44 to -0.20; p < 0.001] units of improvement), but not in autoantibody-negative RA (range 0.10 [95% CI -0.12 to 0.31; p = 0.38] to -0.13 [95% CI -0.34 to 0.07; p = 0.20] units of improvement). Limitations to note were that treatment was not randomized-but it was protocolized and instrumental variable analysis was used to obtain comparable groups-and that a limited spread of ethnicities was included. CONCLUSIONS: Although disease activity has improved in both autoantibody-positive and autoantibody-negative RA in recent decades, the response in long-term outcomes differed. We propose that it is time to subdivide RA into autoantibody-positive RA (type 1) and autoantibody-negative RA (type 2), in the hope that this leads to stratified treatment in RA.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/epidemiologia , Artrite Reumatoide/genética , Adulto , Idoso , Antirreumáticos/efeitos adversos , Antirreumáticos/uso terapêutico , Autoanticorpos/genética , Autoanticorpos/imunologia , Biomarcadores Farmacológicos/sangue , Estudos de Coortes , Progressão da Doença , Feminino , Humanos , Estudos Longitudinais , Masculino , Metotrexato/efeitos adversos , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Índice de Gravidade de Doença
6.
Reumatol Clin ; 16(6): 437-446, 2020.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-32800760

RESUMO

OBJECTIVE: To produce recommendations for patients with rheumatological diseases receiving immunomodulatory and immunosuppressive therapies (conventional drugs, biologicals, and small molecules) during the COVID-19 pandemic. MATERIALS AND METHODS: The recommendations were determined using the Delphi method as an agreement tool. A panel of experts was formed, with academic backgrounds and research experience in rheumatology. A literature search was conducted and 42 questions were generated. The level of agreement was made with 80% of approval by the participants. RESULTS: A group of eleven rheumatologists from 7 cities in the country participated. The response rate was 100% for the three consultation rounds. In the first round, agreement was reached on 35 questions, on 37 in the second round, and on 42 questions in the third round. CONCLUSION: The recommendation for the majority of the pharmacological treatments used in rheumatology is to continue with immunomodulatory or immunosuppressive therapies in patients who do not have the infection, and to suspend it in patients with a diagnosis of SARS-CoV-2/COVID-19.


Assuntos
Antirreumáticos/uso terapêutico , Betacoronavirus , Infecções por Coronavirus/complicações , Pandemias , Pneumonia Viral/complicações , Doenças Reumáticas/complicações , Adulto , Anti-Inflamatórios não Esteroides/efeitos adversos , Anti-Inflamatórios não Esteroides/uso terapêutico , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/uso terapêutico , Antimaláricos/efeitos adversos , Antimaláricos/uso terapêutico , Antirreumáticos/efeitos adversos , Produtos Biológicos/efeitos adversos , Produtos Biológicos/uso terapêutico , Ensaios Clínicos como Assunto , Colômbia , Infecções por Coronavirus/tratamento farmacológico , Técnica Delfos , Interações Medicamentosas , Reposicionamento de Medicamentos , Glucocorticoides/efeitos adversos , Glucocorticoides/uso terapêutico , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/efeitos adversos , Fatores Imunológicos/uso terapêutico , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Estudos Multicêntricos como Assunto , Pneumonia Viral/tratamento farmacológico , Doenças Reumáticas/tratamento farmacológico
7.
J Addict Dis ; 38(4): 580-581, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32752939

RESUMO

During the COVID-19 pandemic caused by the SARS-CoV-2 virus patients with compromised immune systems may be particularly vulnerable. Aside from known causes of immunocompromised states one cause which may have not received due attention is consumption of adulterated recreational drugs. Levamisole-adulterated cocaine poses a particular concern given that documented risk of agranulocytosis and severe neutropenia that may put those exposed at risk of bacterial superinfections and other complications as well as potentially increasing exposure. While oustanding questions remain these risks may warrant inclusion into patient counseling activities by clinicians.


Assuntos
Cocaína , Infecções por Coronavirus/imunologia , Contaminação de Medicamentos , Hospedeiro Imunocomprometido/efeitos dos fármacos , Levamisol/efeitos adversos , Pneumonia Viral/imunologia , Antirreumáticos/efeitos adversos , Infecções por Coronavirus/epidemiologia , Humanos , Pandemias , Pneumonia Viral/epidemiologia
8.
Ann Rheum Dis ; 79(10): 1290-1297, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32788396

RESUMO

OBJECTIVES: To evaluate the incidence of infection in patients with active rheumatoid arthritis (RA) treated with baricitinib, an oral selective Janus kinase (JAK)1 and JAK2 inhibitor. METHODS: Infections are summarised from an integrated database (8 phase 3/2/1b clinical trials and 1 long-term extension (LTE)) with data to 1 April 2017. The 'all-bari-RA' analysis set included patients who received any baricitinib dose. Placebo comparison was based on six studies with 4 mg and placebo to week 24, including four trials with 2 mg (placebo-controlled set). Dose-response assessment was based on four studies with 2 mg and 4 mg, including LTE data (2-4 mg extended set). RESULTS: There were 3492 patients who received baricitinib for 7860 patient-years (PY) of exposure (median 2.6 years, maximum 6.1 years). Treatment-emergent infections were higher for baricitinib versus placebo (exposure-adjusted incidence rate (IR)/100 PY: placebo 75.9, 2 mg 84.0 (p not significant), 4 mg 88.4 (p≤0.001)). The IR of serious infection was similar for baricitinib versus placebo and stable over time (all-bari-RA IR 3.0/100 PY). There were 11 cases of tuberculosis (all-bari-RA IR 0.1/100 PY); all occurred with 4 mg in endemic regions. Herpes zoster (HZ) IR/100 PY was higher for baricitinib versus placebo (placebo 1.0, 2 mg 3.1 (p not significant), 4 mg 4.3 (p≤0.01)); rates remained elevated and stable over time (all-bari-RA 3.3). Opportunistic infections, including multidermatomal HZ, were infrequent in the baricitinib programme (all-bari-RA IR 0.5/100 PY). CONCLUSIONS: Increased rates of treatment-emergent infections including HZ were observed in patients with RA treated with baricitinib, consistent with baricitinib's immunomodulatory mode of action.


Assuntos
Antirreumáticos/efeitos adversos , Artrite Reumatoide/tratamento farmacológico , Azetidinas/efeitos adversos , Hospedeiro Imunocomprometido , Infecções/imunologia , Sulfonamidas/efeitos adversos , Método Duplo-Cego , Humanos , Incidência , Infecções/epidemiologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos
9.
Expert Opin Drug Saf ; 19(11): 1505-1511, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32693646

RESUMO

BACKGROUND: Baricitinib is approved for the treatment of rheumatoid arthritis (RA). The authors retrospectively investigated adverse events (AEs) by data-mining a self-reporting database to better understand toxicities, especially since it has been used during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: A reporting odds ratio (ROR) was used to detect the risk signals from the data in the US Food and Drug Administration (FDA) adverse event reporting system database (FAERS). The definition relied on system organ class (SOCs) and preferred terms (PTs) by the Medical Dictionary for Regulatory Activities (MedDRA). RESULTS: The search retrieved 1,598 baricitinib-associated cases within the reporting period: 86 PTs with significant disproportionality were retained. Infections including 'herpes zoster,' 'oral herpes,' and 'herpes virus infection' were found at a similar rate to those reported in trials, and such events were rare. Reports emerged for several thrombotic adverse events, while these events were also rare. Unexpected safety signals as opportunistic infections were detected. Serious outcomes as death and life-threatening outcomes accounted for 9.76% of the reported cases. CONCLUSIONS: The incidence of these AEs does not appear above the background expected. These data are consistent with routine clinical observations and suggest the importance of pharmacovigilance.


Assuntos
Sistemas de Notificação de Reações Adversas a Medicamentos , Antirreumáticos/efeitos adversos , Azetidinas/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Inibidores de Janus Quinases/efeitos adversos , Farmacovigilância , Sulfonamidas/efeitos adversos , United States Food and Drug Administration , Adulto , Idoso , Idoso de 80 Anos ou mais , Mineração de Dados , Bases de Dados Factuais , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Segurança do Paciente , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Resultado do Tratamento , Estados Unidos , Adulto Jovem
10.
Medicine (Baltimore) ; 99(27): e20824, 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32629668

RESUMO

INTRODUCTION: Glucocorticoids (GCs), especially low-dose GCs, are commonly prescribed for rheumatoid arthritis (RA), although the risk/benefit ratio is controversial. A randomized, double-blind clinical trial was performed to evaluate the efficacy and safety of low-dose oral GCs combined with methotrexate (MTX) and hydroxychloroquine (HCQ) in early RA (ERA). METHODS: Eighty untreated ERA patients were randomized into the trial (GCs + MTX + HCQ) and control (placebo + MTX + HCQ) groups, for 1-year treatment. Therapeutic evaluation indices were American College of Rheumatology (ACR) 20 of ACR, disease activity score (DAS) 28- erythrocyte sedimentation rate (ESR), visual analog scale scores, joint function, health assessment questionnaire-disability index score, morning stiffness duration, C-reaction protein and ESR. The clinical indicators were evaluated pre-treatment and at 1st, 3th, 6th and 12th month of treatment. The MRI data of single joint (ie, the most swollen joint) for each patient were acquired with a revised OMERACT RAMRIS Scoring System before and after treatment. The correlation analysis was adopted to confirm whether the efficacy of GC treatment is related to the time of RA onset. The side effects (eg, gastrointestinal reactions, liver dysfunction, upper respiratory tract infection, leukocyte reduction) were also monitored. RESULTS: At 1st month, 55% and 20% cases in the experimental and control groups achieved ACR20 response, respectively, indicating a significant difference (χ = 16.157, P < .001). This trend continued until 6th month. At 12th month, the number of patients achieved ACR20 response was similar in both groups. At 1st to 6th month, DAS28- ESR scores in the experimental group were significantly lower than control values (all p < .05). The experimental group showed improved inflammation, quality of life and radiological symptoms. Bone erosion remained unchanged in the experimental group, while worsening in control group. Correlation coefficients between RA duration and DAS28-ESR score were 0.496, 0.464, 0.509, and 0.550 at 1st, 3th, 6th, and 12th month, respectively. No differences were found in adverse events between the 2 groups. CONCLUSIONS: Low-dose GCs combined with MTX and HCQ significantly achieves disease remission indexed by ACR20 and DAS28-ESR, and improves clinical and radiological outcomes in ERA patients at the early stage, with superiority over placebo + MTX + HCQ, without enhancing adverse reactions.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Glucocorticoides/uso terapêutico , Hidroxicloroquina/uso terapêutico , Metotrexato/uso terapêutico , Adulto , Antirreumáticos/administração & dosagem , Antirreumáticos/efeitos adversos , Sedimentação Sanguínea , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Glucocorticoides/administração & dosagem , Glucocorticoides/efeitos adversos , Humanos , Hidroxicloroquina/administração & dosagem , Hidroxicloroquina/efeitos adversos , Masculino , Metotrexato/administração & dosagem , Metotrexato/efeitos adversos , Pessoa de Meia-Idade , Qualidade de Vida , Índice de Gravidade de Doença
11.
Heart Rhythm ; 17(11): 1930-1935, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32610165

RESUMO

BACKGROUND: Hydroxychloroquine (HCQ) has been promoted as a potential treatment of coronavirus disease 2019 (COVID-19), but there are safety concerns. OBJECTIVE: The purpose of this study was to determine the effects of HCQ treatment on QT interval. METHODS: We retrospectively studied the electrocardiograms of 819 patients treated with HCQ for rheumatologic diseases from 2000 to 2020. The primary outcome was corrected QT (QTc) interval, by Bazett formula, during HCQ therapy. RESULTS: Mean patient age was 64.0 ± 10.9 years, and 734 patients (90%) were men. Median dosage of HCQ was 400 mg daily, and median (25th-75th percentile) duration of HCQ therapy was 1006 (471-2075) days. Mean on-treatment QTc was 430.9 ± 31.8 ms. In total, 55 patients (7%) had QTc 470-500 ms, and 12 (1.5%) had QTc >500 ms. Chronic kidney disease (CKD), history of atrial fibrillation (AF), and heart failure were independent risk factors for prolonged QTc. In a subset of 591 patients who also had a pretreatment electrocardiogram, mean QTc increased from 424.4 ± 29.7 ms to 432.0 ± 32.3 ms (P <.0001) during HCQ treatment. Of these patients, 23 (3.9%) had either prolongation of QTc >15% or on-treatment QTc >500 ms. Over median 5.97 (3.33-10.11) years of follow-up, 269 patients (33%) died. QTc >470 ms during HCQ treatment was associated with a greater mortality risk (hazard ratio 1.78; 95% confidence interval 1.16-2.71; P = .008) in univariable but not in multivariable analysis. CONCLUSION: HCQ is associated with QT prolongation in a significant fraction of patients. The risk of QT prolongation is higher among patients with CKD, AF, and heart failure, who may benefit from greater scrutiny.


Assuntos
Eletrocardiografia , Hidroxicloroquina , Síndrome do QT Longo , Doenças Reumáticas/tratamento farmacológico , Antirreumáticos/administração & dosagem , Antirreumáticos/efeitos adversos , Fibrilação Atrial/epidemiologia , Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Monitoramento de Medicamentos/métodos , Eletrocardiografia/métodos , Eletrocardiografia/estatística & dados numéricos , Feminino , Humanos , Hidroxicloroquina/administração & dosagem , Hidroxicloroquina/efeitos adversos , Síndrome do QT Longo/induzido quimicamente , Síndrome do QT Longo/diagnóstico , Síndrome do QT Longo/epidemiologia , Masculino , Pessoa de Meia-Idade , Minnesota/epidemiologia , Avaliação de Processos e Resultados em Cuidados de Saúde , Pandemias , Pneumonia Viral/tratamento farmacológico , Insuficiência Renal Crônica/epidemiologia , Estudos Retrospectivos , Doenças Reumáticas/mortalidade , Risco Ajustado , Fatores de Risco
12.
Brasília; CONITEC; jul. 2020.
Não convencional em Português | BRISA/RedTESA | ID: biblio-1121202

RESUMO

INTRODUÇÃO: A artrite psoriaca (AP), doenca articular inflamatoria associada a psoriase, pertencente ao grupo das espondiloartrites, reune manifestacoes cutaneas e articulares. Tem uma prevalencia de aproximadamente 1 a 2 por 1.000 na populacao em geral. Cerca de 30% dos pacientes com psoriase desenvolvem AP. No exame fisico, estao presentes dor oriunda do estresse, sensibilidade das linhas articulares e derrames nas articulacoes afetadas, geralmente em uma distribuicao assimetrica. O tratamento preconizado no Protocolo Clinico e Diretrizes Terapeuticas de Artrite Psoriaca e disponivel no SUS e a base de anti-inflamatorios nao esteroidais, glicocorticoides, medicamentos modificadores do curso da doenca (MMCD) sinteticos e biologicos e Inibidor de citocinas anti-interleucina (IL)-17. TECNOLOGIA: Citrato de tofacitinibe (XeljanzR). PERGUNTA: Tofacitinibe e eficaz e seguro para o tratamento da artrite psoriaca ativa moderada a grave em pacientes adultos que nao responderam ou sao intolerantes ao tratamento previo com MMCD sinteticos ou biologicos? EVIDÊNCIAS CIENTÍFICAS: Foram selecionados dois estudos fase III, ensaios clinicos randomizados avaliando eficacia e seguranca do tofacitinibe em pacientes tratados previamente com medicamentos modificadores da doenca sinteticos e anti-TNF. No estudo com pacientes tratados previamente com anti-TNF, ACR50 em 3 meses foi de 15% para placebo, 30% para tofacitinibe de 5mg( p = 0,003), e 28% para tofacitinibe de 10 mg (p = 0,007). Ja no estudo de pacientes tratados previamente com MMCD sinteticos em 3 meses as taxas de resposta foram 10% para placebo, 30 % para tofacitinibe 5mg e 42% para tofacitinibe 10 mg (p < 0,001 para as duas comparacoes. AVALIAÇÃO ECONÔMICA: Foi apresentada uma analise de custo-miniminizacao, uma vez que os estudos de comparacao indireta do tofacitinibe com seus comparadores demonstraram efetividade semelhante. O custo anual do tratamento por paciente, considerando-se apenas o preco do tofacitinibe proposto pelo demandante, foi de R$ 11.074,10. Em relacao aos seus comparadores, se incorporado, pode gerar uma reducao de custos que variou de -R$ 1.336,74 (em relacao ao Adalimumabe) a -R$ 14.940,94 (em relacao ao Imfliximabe). AVALIAÇÃO DE IMPACTO ORÇAMENTÁRIO: Em todos os cenarios propostos o uso do tofacitinibe gerou economia de recursos. O impacto orcamentario do tofacitinibe ao custo proposto pelo demandante em 1 ano foi de ­R$ 41,4 milhoes , variando nos cenarios entre ­R$ 9,1 milhoes a ­R$ 64,1 milhoes e em 5 anos foi de ­R$ 240,6 milhoes variando nos cenarios entre ­R$ 52,8 milhoes a ­R$ 372,1 milhoes. A estimativa da populacao pelo metodo demanda aferida contemplou toda populacao com AP, e nao apenas a populacao com AP moderada a grave, fazendo com que estes valores estejam superestimados. MONITORAMENTO DO HORIZONTE TECNOLÓGICO: Foram detectadas no horizonte seis potenciais tecnologias para o tratamento de pacientes com artrite psoriaca ativa moderada a grave com resposta inadequada ou intolerantes ao tratamento previo com MMCD sinteticos ou biológicos. CONSIDERAÇÕES: O citrato de tofacitinibe e uma tecnologia ja incorporada no SUS para outras indicacoes. As poucas evidencias cientificas disponiveis, possivelmente em virtude do recente registro desta nova indicacao junto as agencias reguladoras, e que atenderam a pergunta estruturada aqui proposta, demonstraram que o medicamento possui eficacia semelhante aos MMCD biologicos a um custo inferior. Sua administracao por via oral favorece a adesao ao tratamento na maioria dos casos, alem de reduzir custos anuais de tratamento. Deve ser usado em associacao aos MMCD sinteticos. A evidencia atualmente disponivel sobre eficacia e seguranca do tofacitinibe para tratamento de artrite psoriaca e baseada em apenas 2 ensaios clinicos randomizados, estudos fase III, com risco de vies incerto e grau de recomendacao fraco a favor da tecnologia. RECOMENDAÇÃO PRELIMINAR DA CONITEC: Os membros do plenario presentes na 85a reunião ordinaria, realizada nos dias 04 e 05 de fevereiro de 2020, indicaram que o tema fosse submetido a consulta publica com recomendacao preliminar favoravel a incorporacao ao SUS de tofacitinibe para tratamento de artrite psoriaca ativa moderada a grave em pacientes adultos que nao respondem ou sao intolerantes ao tratamento previo com medicamentos modificadores do curso da doenca (MMCD) sinteticos ou biologicos. Considerou-se que as evidencias apresentadas demonstram que o tofacitinibe possui eficacia semelhante aos medicamentos ja disponiveis no SUS, alem de ser um medicamento oral, o que poderia favorecer a adesao ao tratamento. Alem disso, a sua incorporacao geraria economia de recursos em cenarios que contemplam os demais medicamentos biologicos atualmente incorporados ao SUS para a mesma condicao clinica. A materia foi disponibilizada em consulta publica. CONSULTA PÚBLICA: Houve 103 contribuicoes, 18 tecnico-cientificas e 85 de experiencia ou opiniao, sobre a recomendacao preliminar da Conitec. Apenas 2 contribuicoes foram contrarias, porem sem nenhuma argumentacao. Nao foram adicionadas referencias que alterassem as analises da evidencia. RECOMENDAÇÃO FINAL: Os membros da Conitec presentes na 88a reuniao ordinaria, no dia 07 de julho de 2020, deliberaram por unanimidade, recomendar a incorporacao do citrato de tofacitinibe para o tratamento de pacientes adultos com artrite psoriaca ativa moderada a grave intolerantes ou com falha terapeutica aos medicamentos modificadores do curso da doença sinteticos ou biologicos, conforme o Protocolo Clinico e Diretrizes Terapeuticas do Ministerio da Saude. Foi assinado o Registro de Deliberacao no 529/2020. DECISÃO: incorporar o citrato de tofacitinibe para o tratamento de pacientes adultos com artrite psoriaca ativa moderada a grave intolerantes ou com falha terapeutica aos medicamentos modificadores do curso da doenca sinteticos ou biologicos, conforme o Protocolo Clinico e Diretrizes Terapeuticas do Ministerio da Saude, no ambito do Sistema Unico de Saude - SUS, conforme Portaria no 28, publicada no Diario Oficial da Uniao no 160, secao 1, pagina 117, em 20 de agosto de 2020.


Assuntos
Humanos , Artrite Psoriásica/tratamento farmacológico , Anti-Inflamatórios não Esteroides/efeitos adversos , Interleucinas/antagonistas & inibidores , Antirreumáticos/efeitos adversos , Janus Quinases/antagonistas & inibidores , Glucocorticoides/efeitos adversos , Avaliação da Tecnologia Biomédica , Sistema Único de Saúde , Brasil , Análise Custo-Benefício/economia
13.
PLoS One ; 15(7): e0235637, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32628710

RESUMO

BACKGROUND: The high risk of cardiovascular disease is well recognized in rheumatoid arthritis. Type 2 diabetes also attributes to this increase in risk. Rheumatoid arthritis is a chronic inflammatory condition, which aggravates insulin resistance, placing the patients at a higher risk of type 2 diabetes and subsequent cardiovascular outcomes. Methotrexate treatment, as a gold standard anti-inflammatory drug in the treatment of rheumatoid arthritis has shown beneficial effects on cardiovascular health. However, its impact on type 2 diabetes is still unknown. OBJECTIVE: To assess the strength of the association between exposure to methotrexate and the rate of development of type 2 diabetes in rheumatoid arthritis patients. METHODS: All rheumatoid arthritis studies reporting the use of methotrexate as an exposure and type 2 diabetes as an outcome were searched until March 2020 using MEDLINE, Cochrane and Scopus databases. Studies were included if the diagnosis of rheumatoid arthritis was made according to current guidelines or by a rheumatologist, and if there was information about methotrexate exposure and the type 2 diabetes outcome. The author and an independent assessor evaluated the articles for eligibility. Meta-analyses combined relative risk estimates from each study where raw counts were available. RESULTS: Sixteen studies reporting sufficient data for inclusion in the meta-analyses were identified. Methotrexate showed a promising effect on the risk of type 2 diabetes as this risk decreased in rheumatoid arthritis patients using methotrexate (Relative risk 0.48, 95% CI 0.16, 1.43). CONCLUSION: Rheumatoid arthritis patients on methotrexate treatment had a lower risk of developing type 2 diabetes compared to rheumatoid arthritis patients not exposed to methotrexate. This finding highlights the need for future, randomized control trials to confirm the beneficial effect of methotrexate on type 2 diabetes in the rheumatoid arthritis population.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Diabetes Mellitus Tipo 2/diagnóstico , Metotrexato/uso terapêutico , Fatores Etários , Antirreumáticos/efeitos adversos , Artrite Reumatoide/patologia , Diabetes Mellitus Tipo 2/etiologia , Humanos , Metotrexato/efeitos adversos , Risco , Índice de Gravidade de Doença
14.
Travel Med Infect Dis ; 36: 101812, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32645478

RESUMO

BACKGROUND: Hydroxychloroquine (HCQ) is currently being examined for COVID-19. No previous meta-analysis has evaluated its side effects versus placebo. We conducted this meta-analysis to compare the safety of HCQ versus placebo. METHODS: Two authors independently searched PubMed and EMBASE databases for randomized controlled trials (RCTs) of adults comparing the adverse events (AEs) of HCQ versus placebo for any indication. Peto odds ratios (Peto ORs) and 95% confidence intervals (CIs) were calculated based on random-effects models. The heterogeneity (I2) was assessed using Cochran's Q test. RESULTS: Nine RCTs (eight were double-blind) with a total of 916 patients were included. HCQ caused significantly more skin pigmentation than placebo (Peto OR, 4.64; 95% CI, 1.13 to 19.00; P-value = 0.033; I2 = 0%). The increase in other AEs did not reach statistical significance: rash (Peto OR, 1.11; 95% CI, 0.3 to 3.77; P-value = 0.03; I2 = 0%); gastrointestinal AEs (Peto OR, 1.43; 95% CI, 0.55 to 3.72; P-value = 0.46; I2 = 15.17%); headache (Peto OR, 1.94; 95% CI, 0.65 to 5.78; P-value = 0.23; I2 = 9.99%); dizziness (Peto OR, 1.32; 95% CI, 0.49 to 3.52; P-value = 0.58; I2 = 0%); fatigue (Peto OR, 2.13; 95% CI, 0.76 to 5.98; P-value = 0.15; I2 = 0%); and visual AEs (Peto OR, 1.61; 95% CI, 0.76 to 3.41; P-value = 0.22; I2 = 0%). Cardiac toxicity was not reported. CONCLUSIONS: This meta-analysis of RCTs found a significantly higher risk of skin pigmentation in HCQ users versus placebo. More data are needed to evaluate HCQ in the context of COVID-19 treatment.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Antirreumáticos/efeitos adversos , Urticária Crônica/tratamento farmacológico , Glomerulonefrite por IGA/tratamento farmacológico , Infecções por HIV/tratamento farmacológico , Hidroxicloroquina/efeitos adversos , Hiperpigmentação/induzido quimicamente , Doenças Reumáticas/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , Infecções Assintomáticas , Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Tontura/induzido quimicamente , Exantema/induzido quimicamente , Fadiga/induzido quimicamente , Gastroenteropatias/induzido quimicamente , Cefaleia/induzido quimicamente , Humanos , Lúpus Eritematoso Cutâneo/tratamento farmacológico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Osteoartrite/tratamento farmacológico , Pandemias , Pneumonia Viral/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto
15.
Ann Rheum Dis ; 79(9): 1132-1138, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32719044

RESUMO

Secukinumab, ixekizumab and brodalumab are monoclonal antibody therapies that inhibit interleukin (IL)-17 activity and are widely used for the treatment of psoriasis, psoriatic arthritis and ankylosing spondylitis. The promising efficacy results in dermatology and rheumatology prompted the evaluation of these drugs in Crohn's disease and ulcerative colitis, but the onset of paradoxical events (disease exacerbation after treatment with a theoretically curative drug) prevented their approval in patients with inflammatory bowel diseases (IBDs). To date, the pathophysiological mechanisms underlying these paradoxical effects are not well defined, and there are no clear guidelines for the management of patients with disease flare or new IBD onset after anti-IL-17 drug therapy. In this review, we summarise the literature on putative mechanisms, the clinical digestive effects after therapy with IL-17 inhibitors and provide guidance for the management of these paradoxical effects in clinical practice.


Assuntos
Antirreumáticos/efeitos adversos , Colite Ulcerativa/tratamento farmacológico , Doença de Crohn/tratamento farmacológico , Doenças Inflamatórias Intestinais/induzido quimicamente , Interleucina-17/antagonistas & inibidores , Adulto , Anticorpos Monoclonais Humanizados/efeitos adversos , Artrite Psoriásica/tratamento farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Psoríase/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Espondilite Anquilosante/tratamento farmacológico , Resultado do Tratamento
16.
Ann Rheum Dis ; 79(9): 1170-1173, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32532753

RESUMO

BACKGROUND: The susceptibility of patients with rheumatic diseases and the risks or benefits of immunosuppressive therapies for COVID-19 are unknown. METHODS: We performed a retrospective study with patients under follow-up in rheumatology departments from seven hospitals in Spain. We matched updated databases of rheumatology patients with severe acute respiratory syndrome coronavirus 2-positive PCR tests performed in the hospital to the same reference populations. Rates of PCR+ confirmed COVID-19 were compared among groups. RESULTS: Patients with chronic inflammatory diseases had 1.32-fold higher prevalence of hospital PCR+ COVID-19 than the reference population (0.76% vs 0.58%). Patients with systemic autoimmune or immune-mediated disease (AI/IMID) showed a significant increase, whereas patients with inflammatory arthritis (IA) or systemic lupus erythematosus did not. COVID-19 cases in some but not all diagnostic groups had older ages than cases in the reference population. Patients with IA on targeted-synthetic or biological disease-modifying antirheumatic drugs (DMARDs), but not those on conventional-synthetic DMARDs, had a greater prevalence despite a similar age distribution. CONCLUSION: Patients with AI/IMID show a variable risk of hospital-diagnosed COVID-19. Interplay of ageing, therapies and disease-specific factors seem to contribute. These data provide a basis to improve preventive recommendations to rheumatic patients and to analyse the specific factors involved in COVID-19 susceptibility.


Assuntos
Doenças Autoimunes/epidemiologia , Betacoronavirus , Infecções por Coronavirus/epidemiologia , Hospitalização/estatística & dados numéricos , Pneumonia Viral/epidemiologia , Doenças Reumáticas/epidemiologia , Adulto , Distribuição por Idade , Idoso , Antirreumáticos/efeitos adversos , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/epidemiologia , Artrite Reumatoide/virologia , Doenças Autoimunes/tratamento farmacológico , Doenças Autoimunes/virologia , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/virologia , Feminino , Humanos , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/epidemiologia , Lúpus Eritematoso Sistêmico/virologia , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/virologia , Reação em Cadeia da Polimerase , Prevalência , Estudos Retrospectivos , Doenças Reumáticas/tratamento farmacológico , Doenças Reumáticas/virologia , Espanha/epidemiologia
18.
Arthritis Care Res (Hoboken) ; 72(9): 1189-1195, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32526068

RESUMO

OBJECTIVE: To determine health perceptions of patients with rheumatic diseases in the early phase of the coronavirus disease 2019 (COVID-19) pandemic. METHODS: Rheumatology patients at a single center received via text message the Australian Rheumatology Association COVID-19 information sheet and an invitation to participate in a deidentified survey. Patient concerns regarding risks conferred by their rheumatologic disease or medications, impact of receiving the information sheet on the likelihood of staying on medication, and acceptance of telehealth were ascertained. RESULTS: A total of 2,630 patients received the text message, and the survey response rate was 21% (n = 550). The mean ± SD age of the participants was 52 ± 15.2 years, and 75.3% were female. Participants' highest ranked concern was that their medications would increase the severity of their COVID-19 symptoms (76.1%). The highest levels of concern were seen in patients taking combination conventional synthetic disease-modifying antirheumatic drugs (DMARDs) and/or a biologic/targeted synthetic DMARD. There was no association between prednisolone dose and concern. While 63% of patients planned to continue their antirheumatic medications, a further 30% were more likely to continue taking their medications because of receiving the information. Telehealth was acceptable to 98.4% of patients, but 28.1% felt this was only appropriate while infection control measures were in place. CONCLUSION: Concerns regarding the risk of COVID-19 among patients taking antirheumatic drugs are common. Proactive dissemination of information is needed to address misconceptions related to medication risk, improve medication adherence, and minimize the risk of flares. Telehealth is acceptable to most patients during the COVID-19 pandemic.


Assuntos
Antirreumáticos/efeitos adversos , Betacoronavirus , Infecções por Coronavirus/psicologia , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Pneumonia Viral/psicologia , Doenças Reumáticas/psicologia , Atitude Frente a Saúde , Infecções por Coronavirus/prevenção & controle , Feminino , Humanos , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Doenças Reumáticas/tratamento farmacológico , Doenças Reumáticas/virologia , Índice de Gravidade de Doença , Inquéritos e Questionários
19.
Nat Rev Rheumatol ; 16(7): 361-379, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32494054

RESUMO

Patients with rheumatoid arthritis (RA) are at high risk of developing cardiovascular disease (CVD). Inflammation has a pivotal role in the pathogenesis of CVD. RA is an inflammatory joint disease and, compared with the general population, patients with RA have approximately double the risk of atherosclerotic CVD, stroke, heart failure and atrial fibrillation. Although this high risk of CVD has been known for decades, patients with RA receive poorer primary and secondary CVD preventive care than other high-risk patients, and an unmet need exists for improved CVD preventive measures for patients with RA. This Review summarizes the evidence for atherosclerotic CVD in patients with RA and provides a contemporary analysis of what is known and what needs to be further clarified about recommendations for CVD prevention in patients with RA compared with the general population. The management of traditional CVD risk factors, including blood pressure, lipids, diabetes mellitus and lifestyle-related risk factors, as well as the effects of inflammation and the use of antirheumatic medication on CVD risk and risk management in patients with RA are discussed. The main aim is to provide a roadmap of atherosclerotic CVD risk management and prevention for patients with RA.


Assuntos
Antirreumáticos/efeitos adversos , Artrite Reumatoide/complicações , Aterosclerose/fisiopatologia , Doenças Cardiovasculares/prevenção & controle , Adulto , Idoso , Artrite Reumatoide/tratamento farmacológico , Fibrilação Atrial/epidemiologia , Artérias Carótidas/diagnóstico por imagem , Estudos de Casos e Controles , Interações Medicamentosas , Feminino , Insuficiência Cardíaca/epidemiologia , Humanos , Inflamação/patologia , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia , Ultrassonografia/métodos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA