Custeio Baseado em Atividade e Tempo (TDABC) do modelo CEDMAC de terapia assistida para dispensação de medicamentos imunobiológicos para doenças reumatológicas no SUS / Time-Driven Activity Based Costing (TDABC) of the CEDMAC model of assisted therapy for dispensing immunobiological rheumatologic medications at SUS

Objetivos: Mensurar o custo dos procedimentos de infusão de imunobiológicos no modelo CEDMAC (Centro de Dispensação de Medicações de Alto Custo) e estimar o custo minimização integral gerada pela existência desse modelo. Métodos: A metodologia de Custeio Baseado em Atividade e Tempo (TDABC) foi usada para calcular os custos dos procedimentos. Tempos de atividades, capacidades máximas de atendimento e fluxos dos processos internos foram obtidos em entrevistas e validados por meio de acompanhamento de pacientes. Os procedimentos foram categorizados em três tipos: a) aplicação subcutânea, b) infusão endovenosa rápida e c) infusão endovenosa longa. O custo-minimização foi estimado a partir de análise de 2017 para pacientes com artrite reumatoide (AR). Resultados: Ao longo de 2019, foram realizados 12.074 atendimentos no CEDMAC. Desses atendimentos, 60% foram de aplicação subcutânea (custo de R$ 117,90), 30%, de infusão endovenosa rápida (custo de R$ 169,90) e 10%, de endovenosa longa (custo de R$ 217,50). Usando a análise realizada em 2017, foi possível calcular o custo-minimização integral do modelo (uma economia líquida estimada de R$ 1.258.024,26 ao ano) e também extrapolar esses valores para todo o SUS caso o modelo fosse difundido no país (uma economia líquida estimada de R$ 189.401.652,88). Conclusão: Utilizando o método de TDABC, foi possível realizar de maneira rápida e eficiente o custeio dos principais procedimentos realizados no modelo CEDMAC. Essa análise embasará a solicitação da incorporação desses procedimentos na tabela unificada do SUS. Caso os procedimentos sejam incorporados e o modelo CEDMAC, difundido pelo Brasil, estima-se que a economia gerada seja da ordem de 189 milhões de reais ao ano.

Objectives: To measure the costs of immunobiological infusion procedures in the CEDMAC model (Centro de Dispensação de Medicações de Alto Custo) and to estimate the full cost-minimization generated by the existence of this model. Methods: Time-Driven Activity Based Costing (TDABC) methodology was used to calculate the procedures costs. Activity times, service capacities and internal flows were obtained from employee interviews and validated by follow-up with patients. Procedures were categorized into three types: a) subcutaneous, b) intravenous fast infusion, and c) intravenous slow infusion. The full cost-minimization was estimated based on a 2017 analysis of the cost-minimization for rheumatoid arthritis (RA) patients. Results: In 2019, 12,074 patients were attended at CEDMAC. Of these, 60% of infusions were subcutaneous (costing R$ 117.90 each), 30% were fast intravenous infusion (costing R$ 169.90), and 10% were slow intravenous infusion (costing R$ 217.50). Using a 2017 RA analysis, it was possible to calculate the full cost-minimization of the model, with an estimated net savings of R$ 1,258,024.26 per year. The estimated net savings if the model were disseminated throughout the country for the entire SUS would be R$ 189,401,652.88. Conclusion: Using the TDABC method it was possible to quickly and efficiently estimate the cost allocation of the main procedures performed in the CEDMAC model. This analysis will support the request for incorporating these procedures into SUS. If the procedures were incorporated, and the CEDMAC model was disseminated throughout Brazil, the savings generated by this initiative could be up to 189 million reais per year.

Increment of immunogenicity after third dose of a homologous inactivated SARS-CoV-2 vaccine in a large population of patients with autoimmune rheumatic diseases.

OBJECTIVE: To determine the immunogenicity of the third dose of CoronaVac vaccine in a large population of patients with autoimmune rheumatic diseases (ARD) and the factors associated with impaired response. METHODS: Adult patients with ARD and age-balanced/sex-balanced controls (control group, CG) previously vaccinated with two doses of CoronaVac received the third dose at D210 (6 months after the second dose). The presence of anti-SARS-CoV-2 S1/S2 IgG and neutralising antibodies (NAb) was evaluated previously to vaccination (D210) and 30 days later (D240). Patients with controlled disease suspended mycophenolate mofetil (MMF) for 7 days or methotrexate (MTX) for 2 weekly doses after vaccination. RESULTS: ARD (n=597) and CG (n=199) had comparable age (p=0.943). Anti-S1/S2 IgG seropositivity rates significantly increased from D210 (60%) to D240 (93%) (p<0.0001) in patients with ARD. NAb positivity also increased: 38% (D210) vs 81.4% (D240) (p<0.0001). The same pattern was observed for CG, with significantly higher frequencies for both parameters at D240 (p<0.05). Multivariate logistic regression analyses in the ARD group revealed that older age (OR=0.98, 95% CI 0.96 to 1.0, p=0.024), vasculitis diagnosis (OR=0.24, 95% CI 0.11 to 0.53, p<0.001), prednisone ≥5 mg/day (OR=0.46, 95% CI 0.27 to 0.77, p=0.003), MMF (OR=0.30, 95% CI 0.15 to 0.61, p<0.001) and biologics (OR=0.27, 95% CI 0.16 to 0.46, p<0.001) were associated with reduced anti-S1/S2 IgG positivity. Similar analyses demonstrated that prednisone ≥5 mg/day (OR=0.63, 95% CI 0.44 to 0.90, p=0.011), abatacept (OR=0.39, 95% CI 0.20 to 0.74, p=0.004), belimumab (OR=0.29, 95% CI 0.13 to 0.67, p=0.004) and rituximab (OR=0.11, 95% CI 0.04 to 0.30, p<0.001) were negatively associated with NAb positivity. Further evaluation of COVID-19 seronegative ARD at D210 demonstrated prominent increases in positivity rates at D240 for anti-S1/S2 IgG (80.5%) and NAb (59.1%) (p<0.0001). CONCLUSIONS: We provide novel data on a robust response to the third dose of CoronaVac in patients with ARD, even in those with prevaccination COVID-19 seronegative status. Drugs implicated in reducing immunogenicity after the regular two-dose regimen were associated with non-responsiveness after the third dose, except for MTX. Trial registration number NCT04754698.

Modelo de terapia assistida para dispensação de medicamentos imunobiológicos para artrite reumatoide no Sistema Único de Saúde: uso racional de recursos reduz despesas / Assisted therapy model for dispensing immunobiological drugs for rheumatoid arthritis by the Brazilian Unified Health System: rational use of resources reduces expenses

Objetivo: A incorporação dos imunobiológicos para tratamento da artrite reumatoide (AR) no Sistema Único de Saúde (SUS) representou um avanço significativo, porém teve um impacto importante no orçamento. Como o modelo vigente de dispensação direta ao paciente apresentava deficiências, implementou-se o modelo do CEDMAC de terapia assistida com foco no uso racional, visando minimizar despesas e potencializar o alcance. Entretanto, não há dados que comparem os dois modelos. Assim, esse estudo objetivou comparar o número de frascos efetivamente dispensados pelo modelo do CEDMAC à dispensação direta e avaliar seu impacto financeiro. Métodos: Foram incluídos atendimentos de pacientes com AR no CEDMAC em 2015, cujo imunobiológico foi fornecido pelo Ministério da Saúde. Foram registrados medicamento e dose recebidos, dose prescrita, número de frascos, cancelamentos por contraindicação e faltas. Como comparação, foi estimado o número de frascos que seriam entregues pela dispensação direta. Calculou-se a diferença entre o número total de frascos dispensados pelos dois sistemas e o impacto financeiro pelo valor de aquisição em 2015. Resultados: Em 2015, o CEDMAC realizou 3.784 atendimentos para pacientes com AR. O total de frascos de imunobiológicos prescritos foi de 10.000 frascos e 1.946 (19,5%) não foram utilizados por otimização de frascos, contraindicações ou absenteísmo. Os frascos não utilizados reduziram as despesas em R$ 806.132,62. A expansão do modelo para todo SUS reduziria as despesas em R$ 121.110.388,27. Conclusão: O modelo de terapia assistida do CEDMAC reduz consideravelmente o volume de frascos dispensados e pode trazer uma relevante redução de despesas no fornecimento dos imunobiológicos para AR no SUS.

Objective: The incorporation of immunobiologicals for the treatment of rheumatoid arthritis (RA) in the Brazilian Unified Health System (SUS) represented a significant advance but had an important impact on the budget. As the current model of direct delivery to the patient presented deficiencies, the CEDMAC model of assisted therapy focusing on rational use was implemented to minimize expenses and increase access. However, there is no data comparing the two models. Thus, this study aimed to compare the number of vials effectively dispensed by the CEDMAC model compared to direct delivery and to evaluate its financial impact. Methods: We included RA patients attended at CEDMAC during 2015, whose immunobiological was provided by Ministry of Health. Drug and dose received, prescribed dose, number of vials, cancellations due to contraindication and absences were recorded. As comparison, the number of vials that would be delivered by the direct delivery model were estimated. Savings were calculated by the difference between the total number of vials dispensed by the two systems and the financial impact by acquisition value in 2015. Results: During 2015, CEDMAC performed 3,784 consultations for RA patients. The total number of immunobiological vials prescribed was 10,000 vials and 1,946 (19.5%) were not used for vial optimization, contraindications or absenteeism. Saved vials reduced expenses by R$ 806,132.62. The expansion of the model for all SUS would reduce expenses by R$ 121,110,388.27. Conclusion: CEDMAC's model of assisted therapy considerably reduces the volume of dispensed vials and can bring significant cost offsets in the supply of RA immunobiologicals by SUS.

Assisted therapy model for dispensing immunobiological drugs for rheumatoid arthritis by the Brazilian Unified Health System: rational use of resources reduces expenses

Objective: The incorporation of immunobiological agents for rheumatoid arthritis (RA) treatment at the Brazilian Unified Health System (SUS) represented a significant advance but had an important impact on the budget. As the current model of direct patient delivery had deficiencies, the CEDMAC model of assisted therapy was implemented to focus on rational use to minimize expenses and increase access. However, there is no data to compare the two models. Thus, this study aimed to compare the number of bottles effectively dispensed by the CEDMAC model to direct dispensing and assess its financial impact. Methods: Care of RA patients at CEDMAC in 2015, whose immunobiological drugs were provided by the Ministry of Health, were included. Drug and dose received, prescribed dose, the number of bottles, cancellations due to contraindication, and absences were recorded. As a comparison, the number of bottles that would be delivered by direct dispensing was estimated. The difference between the total number of bottles dispensed by the two systems and the financial impact of the purchase price in 2015 was calculated. Results: In 2015, CEDMAC provided 3,784 consultations for RA patients. The total number of bottles of immunobiological agents prescribed was 10,000 bottles, and 1,946 (19.5%) were not used for bottle optimization, contraindications, or absenteeism. Unused bottles reduced expenses by R$ 806,132.62. The expansion of the model to the entire SUS would reduce costs by R$ 121,110,388.27. Conclusion: The CEDMAC assisted therapy model considerably reduces the volume of dispensed bottles and can significantly reduce expenses in the supply of immunobiological agents for RA at SUS.

Ankylosing spondylitis and psoriatic arthritis: revisiting screening of latent tuberculosis infection and its follow-up during anti-tumor necrosis factor therapy in an endemic area.

OBJECTIVES: To retrospectively evaluate the performance and distinctive pattern of latent tuberculosis (TB) infection (LTBI) screening and treatment in patients with ankylosing spondylitis (AS) and psoriatic arthritis (PsA) under anti-tumor necrosis factor (TNF) therapy and determine the relevance of re-exposure and other risk factors for TB development. METHODS: A total of 135 and 83 patients with AS and PsA, respectively, were evaluated for LTBI treatment before receiving anti-TNF drugs via the tuberculin skin test (TST), chest radiography, and TB exposure history assessment. All subjects were evaluated for TB infection at 3-month intervals. RESULTS: The patients with AS were more often treated for LTBI than were those with PsA (42% versus 30%, p=0.043). The former also presented a higher frequency of TST positivity (93% versus 64%, p=0.002), although they had a lower frequency of exposure history (18% versus 52%, p=0.027) and previous TB (0.7% versus 6%, p=0.03). During follow-up [median, 5.8 years; interquartile range (1QR), 2.2-9.0 years], 11/218 (5%) patients developed active TB (AS, n=7; PsA, n=4). TB re-exposure was the main cause in seven patients (64%) after 12 months of therapy (median, 21.9 months; IQR, 14.2-42.8 months) and five LTBI-negative patients. TB was identified within the first year in four patients (36.3%) (median, 5.3 months; IQR, 1.2-8.8 months), two of whom were LTBI-positive. There was no difference in the TB-free survival according to the anti-TNF drug type/class; neither synthetic drug nor prednisone use was related to TB occurrence (p>0.05). CONCLUSION: Known re-exposure is the most critical factor for incident TB cases in spondyloarthritis. There are also some distinct features in AS and PsA LTBI screening, considering the higher frequency of LTBI and TST positivities in patients with AS. Annual risk reassessment taking into consideration these peculiar features and including the TST should be recommended for patients in endemic countries.

Ankylosing spondylitis and psoriatic arthritis: revisiting screening of latent tuberculosis infection and its follow-up during anti-tumor necrosis factor therapy in an endemic area

OBJECTIVES: To retrospectively evaluate the performance and distinctive pattern of latent tuberculosis (TB) infection (LTBI) screening and treatment in patients with ankylosing spondylitis (AS) and psoriatic arthritis (PsA) under anti-tumor necrosis factor (TNF) therapy and determine the relevance of re-exposure and other risk factors for TB development. METHODS: A total of 135 and 83 patients with AS and PsA, respectively, were evaluated for LTBI treatment before receiving anti-TNF drugs via the tuberculin skin test (TST), chest radiography, and TB exposure history assessment. All subjects were evaluated for TB infection at 3-month intervals. RESULTS: The patients with AS were more often treated for LTBI than were those with PsA (42% versus 30%, p=0.043). The former also presented a higher frequency of TST positivity (93% versus 64%, p=0.002), although they had a lower frequency of exposure history (18% versus 52%, p=0.027) and previous TB (0.7% versus 6%, p=0.03). During follow-up [median, 5.8 years; interquartile range (1QR), 2.2-9.0 years], 11/218 (5%) patients developed active TB (AS, n=7; PsA, n=4). TB re-exposure was the main cause in seven patients (64%) after 12 months of therapy (median, 21.9 months; IQR, 14.2-42.8 months) and five LTBI-negative patients. TB was identified within the first year in four patients (36.3%) (median, 5.3 months; IQR, 1.2-8.8 months), two of whom were LTBI-positive. There was no difference in the TB-free survival according to the anti-TNF drug type/class; neither synthetic drug nor prednisone use was related to TB occurrence (p>0.05). CONCLUSION: Known re-exposure is the most critical factor for incident TB cases in spondyloarthritis. There are also some distinct features in AS and PsA LTBI screening, considering the higher frequency of LTBI and TST positivities in patients with AS. Annual risk reassessment taking into consideration these peculiar features and including the TST should be recommended for patients in endemic countries.

Dermatomiosite e polimiosite: da imunopatologia à imunoterapia (imunobiológicos) / Dermatomyositis and polymyositis: from immunopathology to immunotherapy (immunobiologics)

As miopatias inflamatórias idiopáticas (MII), das quais fazem parte a dermatomiosite (DM) e a polimiosite (PM), são doenças sistêmicas crônicas associadas a alta morbidade e incapacidade funcional. O tratamento atual baseia-se na corticoterapia e no uso de imunossupressores, porém uma parcela considerável dos pacientes é refratária à terapia tradicional. Isso tem levado à tentativa de uso de imunobiológicos nesses pacientes, tendo por fundamento a fisiopatogênese das MII. Do ponto de vista imunopatológico, há diferenças entre PM e DM: a primeira está mais relacionada à imunidade celular, enquanto na segunda o papel humoral parece mais importante. Em ambas, porém, são descritas concentrações elevadas de interleucinas pró-inflamatórias (TNF, IL-1, IL-6) e aumento da expressão de moléculas relacionadas à coestimulação dos linfócitos T - nessas condições, parece racional o uso da terapia biológica. Considerando os imunobiológicos disponíveis, são escassos os dados de trabalhos abertos na literatura, compostos principalmente por séries e relatos de casos. Os bloqueadores do TNF apresentam resultados conflitantes sem evidência de boa resposta ao tratamento. A terapia anti-CD20 possui os resultados mais promissores. É extremamente escassa a informação sobre o bloqueio da coestimulação do linfócito T e a terapia anti- IL-6, que impede qualquer consideração. Dessa maneira, o uso de imunobiológicos em MII ainda permanece como fronteira a ser explorada. A terapia biológica pode ter papel relevante no tratamento das MII refratárias à terapia convencional; no entanto, novos estudos prospectivos com base em parâmetros objetivos de resposta ao tratamento são necessários. Até o momento, a terapia anti-CD20 parece ser a mais promissora no tratamento das MII refratárias.

Idiopathic inflammatory myopathies (IIM), which include dermatomyositis (DM) and polymyositis (PM), are chronic systemic diseases associated with high morbidity and functional disability. Current treatment is based on the use of glucocorticoids and immunosuppressive drugs, but a considerable number of patients is refractory to traditional therapy. That has led to the attempted use of biologics based on the physiopathogenesis of IIM. From the immunopathological viewpoint, PM and DM differ: the former is more related to cellular immunity, while the latter, to humoral immunity. In both, however, elevated concentrations of proinflammatory interleukins (TNF, IL-1, IL-6) and increased expression of molecules related to costimulation of T lymphocytes have been described; thus, the use of biologics in those conditions seems reasonable. Considering the biologics available, open-label studies are scarce, comprising mainly case reports and series. TNF blockers have yielded conflicting results, with no evidence of good response to treatment. The anti-CD20 therapy has the most promising results. Data on T lymphocyte costimulation blockade and anti-IL-6 therapy are extremely scarce, preventing any consideration. Thus, the use of biologics in IIM still remains an unconquered frontier. Biologics may have an important role in the management of IIM refractory to conventional therapy, but further prospective studies based on objective parameters of response to treatment are needed. So far, anti-CD20 therapy seems to be the most promising treatment for refractory IIM.

Efeito da inflamação no peptídeo natriurético atrial (NT-proBNP) em pacientes com espondilite anquilosante ativa durante terapia anti-TNF / Effect of inflammation on atrial natriuretic peptide (NT-proBNP) levels in active ankylosing spondylitis patients receiving anti-TNF therapy

Introdução: O fragmento amino-terminal do pró-peptídeo natriurético do tipo B (NT-proBNP) é um forte marcador de doença cardiovascular com evidências recentes de que a inflamação também pode influenciar seus valores. A diferenciação dessa variável de confusão é de particular interesse nas doenças reumáticas. Objetivos: Avaliar o comportamento dos valores de NT-proBNP em pacientes com espondilite anquilosante (EA) pré e pós uso de bloqueadores de TNF para determinar a possível associação entre os valores de NT-proBNP e os parâmetros inflamatórios. Métodos: Quarenta e cinco pacientes consecutivos com EA sem evidência prévia ou atual de doença cardiovascular ou disfunção miocárdica sistólica e que eram elegíveis para terapia anti-TNF foram incluídos prospectivamente. Todos os pacientes receberam bloqueadores de TNF e foram avaliados para concentrações circulantes de NT-proBNP, parâmetros clínicos e laboratoriais de atividade de doença, fatores de risco cardiovasculares tradicionais e ecodopplercardiografia convencional e tecidual no momento da inclusão e após seis meses de tratamento. Resultados: No momento da inclusão, todos os pacientes tinham EA ativa, os valores de NT-proBNP tinham uma mediana de 36 (20-72) pg/mL e 11% dos valores estavam altos mesmo na ausência de alteração miocárdica sistólica. A análise de regressão linear múltipla revelou que esse peptídeo estava independentemente correlacionado com o VHS (p < 0,001), com a idade dos pacientes (p = 0,01) e com a pressão de pulso (p = 0,01) no momento da inclusão. Após seis meses, todos os parâmetros relacionados a doença de base melhoraram e os valores de NT-proBNP se reduziram significativamente [24 (16-47) pg/mL, p = 0,037] quando comparados com os valores do momento da inclusão. As mudanças nos valores de NT-proBNP correlacionaram-se positivamente com as mudanças nos valores do VHS (r = 0,41, p = 0.006). Os fatores de risco cardiovasculares avaliados permaneceram estáveis durante o seguimento...

Introduction: N-terminal pro-brain natriuretic peptide (NT-proBNP) is a strong marker of cardiovascular disease with recent evidence that inflammation may also influence its levels; discrimination of this confounding variable is of particular interest in rheumatic diseases. Objectives: to evaluate NT-proBNP in ankylosing spondylitis (AS) patients pre- and post-TNF blocker to determine the possible association between NT-proBNP levels and inflammatory parameters. Methods: Forty-five consecutive AS patients without previous/current cardiovascular disease or systolic myocardial dysfunction, who were eligible to anti-TNF therapy, were prospectively enrolled. All patients received TNF blockers and they were evaluated for circulating NT-proBNP levels, clinical and laboratory parameters of disease activity, traditional cardiovascular risk factors, and conventional and tissue Doppler imaging echocardiography at baseline (BL) and six months after (6M) treatment. Results: At BL, all patients had active AS, NT-proBNP levels had a median of 36 (20-72) pg/mL and 11% were high in spite of no systolic alteration. Multiple linear regression analysis revealed that this peptide, at BL, was independently correlated with ESR (p < 0.001), age (p = 0.01) and pulse pressure (p = 0.01). After 6M, all disease parameters improved and NT-proBNP levels were significantly reduced [24 (16-47) pg/mL, p = 0.037] compared to BL. Changes in NT-proBNP were positively correlated with ESR changes (r = 0.41, p = 0.006). Cardiovascular risk factors remained stable during follow-up. Conclusion: our data suggests that elevations of NT-proBNP should be interpreted with caution in active AS patients with no other evidence of cardiovascular disease. The short-term reduction of NT-proBNP levels in these patients receiving anti-TNF therapy appears to reflect an improvement in inflammatory status...

Pesquisa de autoanticorpos em pacientes com artrite psoriásica sob terapia anti-TNFα / Autoantibodies in patients with psoriatic arthritis on anti-TNFα therapy

INTRODUÇÃO: A terapia imunobiológica anti-TNFα tem-se mostrado efetiva no tratamento de pacientes com artrite psoriásica (APs) refratária. No entanto, não está bem definido o risco de desenvolvimento de autoanticorpos comumente encontrados nas doenças reumatológicas em pacientes com APs na vigência desse tratamento. OBJETIVO: avaliar a indução de autoanticorpos específicos durante a terapia anti-TNFα em pacientes com APs. PACIENTES E MÉTODOS: Foram analisadas amostras de soro de 23 pacientes com APs (mulheres: 61 por cento, idade: 45,04 ± 12,68 anos, quadro poliarticular: 69,6 por cento, duração da doença: 13,3 ± 7,7 anos, infliximabe: 82,60 por cento) obtidas imediatamente antes (basal) e cerca de um ano após a introdução da terapia anti-TNF (última amostra) (385 ± 131,45 dias). A pesquisa incluiu a detecção de anticorpos antinucleares (ANA) e anticorpos para dsDNA (imunofluorescência indireta em células Hep-2 e em Crithidia luciliae, respectivamente); RNP e Sm (hemaglutinação passiva); Ro/SS-A e/ou La/SS-B, cromatina, histona, peptídeo citrulinado (CCP) e cardiolipina (ELISA). RESULTADOS: A pesquisa basal de ANA revelou positividade em 47,8 por cento dos pacientes, com predomínio do padrão nuclear homogêneo (81,8 por cento). Todas as amostras de soro testadas foram negativas para fator reumatoide e anticorpos anticardiolipina, RNP, Sm, Ro/SS-A, La/SS-B, histona e dsDNA, enquanto dois pacientes apresentaram positividade para anticromatina e um para anti-CCP. Todas as amostras de ANA positivas no tempo basal, exceto uma, mantiveram essa reatividade após a introdução da terapia anti-TNF. Reatividade "de novo" ANA foi observada em quatro dos pacientes originalmente negativos (33,3 por cento). Anticorpos anti-Ro/SS-A, La/SS-B, cardiolipina, histona, dsDNA e fator reumatoide foram sistematicamente negativos em todas as amostras finais de soro testadas e positividade anticromatina foi detectada em outros três...

INTRODUCTION: Anti-TNFα therapy has been effective in the treatment of patients with refractory psoriatic arthritis (PSA). However, the risk of developing autoantibodies commonly found in rheumatic diseases in PSA patients undergoing this therapy is not clear. OBJECTIVE: To evaluate the induction of specific autoantibodies after anti-TNFα therapy in PSA patients. PATIENTS AND METHODS: Serum samples from 23 PSA patients (women: 61 percent, age: 45.04 ± 12.68 years, polyarticular: 69.6 percent, disease duration: 13.3 ± 7.7 years, infliximab: 82.60 percent) obtained immediately before (baseline) and approximately one year after the introduction of anti-TNF therapy (last sample) (385 ± 131.45 days), were analyzed. The analysis included detection of antinuclear antibodies (ANA) and anti-dsDNA antibodies (indirect immunofluorescence on Hep-2 cells and Crithidia luciliae, respectively); anti-RNP and anti-Sm (passive hemagglutination); and anti-Ro/ SS-A and/or anti-La/SS-B, anti-chromatin, anti-histones, anti-citrullinated peptide (CCP), and anti-cardiolipin (ELISA) antibodies. RESULTS: At baseline, ANA was positive in 47.8 percent of patients, with predominance of homogeneous nuclear pattern (81.8 percent). All baseline serum samples were negative for rheumatoid factor and antibodies to cardiolipin, RNP, Sm, Ro/SS-A, anti-La/SS-B, anti-histone, and anti-dsDNA antibodies, while two patients were positive for anti-chromatin and one for anti-CCP. All ANA-positive samples at baseline, except for one, remained positive after the introduction of anti-TNF therapy; however, de novo ANA reactivity was observed in four originally negative patients (33.3 percent). Anti-Ro/SS-A, La/SS-B, cardiolipin, histones, dsDNA, and rheumatoid factor antibodies remained negative in all final serum samples tested, and anti-chromatin positivity was detected in three other patients. CONCLUSION: Our findings have shown that anti-TNF therapy induced ANA positivity...

Complicações imediatas de 3.555 aplicações de agentes anti-TNFα / Immediate complications of 3, 555 injections of anti-TNFα

OBJETIVO: Avaliar as complicações imediatas da aplicação de agentes anti-TNFα no Centro de Dispensação de Medicação deAlto Custo do HC-FMUSP. PACIENTES E MÉTODOS: Foram incluídos todos os pacientes que receberam agentes anti-TNFα entre agosto/2007 e março/2009.As complicações imediatas (até 1 hora após o término da aplicação) foram classificadas em leves (cefaleia, rash, tontura, prurido, náuseas), moderadas (febre, urticária, palpitação, dor torácica, dispneia, variação da pressão arterial de 20 a 40 mmHg) ou graves (febre com calafrios, dispneia com sibilância, variação da pressão arterial > 40 mmHg). RESULTADOS: Foram avaliados 242 pacientes: 94 (39 por cento) com artrite reumatoide, 64 (26 por cento) com espondilite anquilosante, 32 (13 por cento) com artrite psoriásica, 26 (11 por cento) com artrite idiopática juvenil e 27 (11 por cento) com outros diagnósticos. O número total de aplicações foi de 3.555, sendo 992 (28 por cento) de adalimumabe, 1.546 (43 por cento) de etanercepte e 1.017 (29 por cento) de infliximabe. Complicações imediatas foram observadas em 39/242 (16 por cento) pacientes. As complicações ocorreram em 45/3.555 (1,2 por cento) aplicações. Estas foram mais frequentes com infliximabe comparado com adalimumabe (3,7 por cento vs. 0,5 por cento, P < 0,0001), e com etanercepte (3,7 por cento vs. 0,25 por cento, P < 0,0001). As complicações foram: leves 14/45 (31 por cento), moderadas 21/45 (47 por cento) e graves 10/45 (22 por cento); ocorreram principalmente nos primeiros seis meses de tratamento (56 por cento) e nas aplicações endovenosas, predominantemente na primeira hora de infusão (76 por cento). CONCLUSÃO: As reações agudas, apesar de raras, são potencialmente graves e ocorrem principalmente nas primeiras aplicações tanto no uso de medicações endovenosas como de subcutâneas...

OBJECTIVE: To evaluate the immediate complications of anti-TNFα drugs at the "Center for Dispensation of High Cost Medications" of HC-FMUSP. PATIENTS AND METHODS: All patients who received anti-TNFα agents between August 2007 and March 2009 were included in this study. Immediate complications (up to 1 hour after the injection) were classified as mild (headache, rash, dizziness, itching, nausea), moderate (fever, urticaria, palpitation, chest pain, dyspnea, blood pressure variations between 20 and 40 mmHg), or severe (fever with chills, dyspnea with wheezing, variations in blood pressure > 40 mmHg). RESULTS: Two hundred and forty-two patients were evaluated: 94 (39 percent) with rheumatoid arthritis, 64 (26 percent) with ankylosing spondylitis, 32 (13 percent) with psoriatic arthritis, 26 (11 percent) with juvenile idiopathic arthritis; and 27 (11 percent) with other diagnoses. A total of 3,555 injections were administered: 992 (28 percent) adalimumab, 1,546 (43 percent) etanercept, and 1,017 (29 percent) infliximab. Immediate adverse events were observed in 39/242 (16 percent) patients. Injectionrelated complications were observed in 46/3,555 (1.2 percent) injections. They were more common with infliximab than adalimumab (3.7 percent vs. 0.5 percent, P < 0.0001) and etanercept (3.7 percent vs. 0.25 percent, P < 0.0001). Complications were classified as mild 14/45 (31 percent), moderate 21/45 (47 percent), and severe 10/45 (22 percent), and occurred mainly in the first six months of treatment (56 percent) and after intravenous injections, especially (76 percent) in the first hour. CONCLUSION: Although rare, acute reactions can be severe, being observed more commonly after the initial injections, both intravenous and subcutaneous...

Frequency of antibodies against the etiologic agents of acquired imunodeficiency syndrome, syphilis, hepatitis B and C, and Chagas' disease in patients with rheumatic diseases treated with anti-tumor necrosis factor / Frequência de anticorpos aos agentes etiológicos da síndrome da imunodeficiência adquirida, sífilis, hepatites virais B e C e doença de Chagas em pacientes reumatológicos em tratamento com antifator de necrose tumoral (Tumor Necrosis Factor - TNF)

INTRODUÇÃO: Os pacientes reumatológicos em terapia com antifator de necrose tumoral (anti-TNF, Tumor Necrosis Factor) são considerados imunodeprimidos. Neste sentido, a pesquisa de doenças infecciosas nesta população é imperiosa devido à alta morbidade e, por vezes, mortalidade associada a este quadro. OBJETIVOS: O presente trabalho teve por objetivo avaliar a frequência de soropositividade para os seguintes agentes infecciosos: Treponema pallidum (sífilis), Trypanosoma cruzii (doença de Chagas), vírus da imunodeficiência humana adquirida (Human imunnodeficiency Virus - HIV) e hepatites B e C (HBV e HCV, respectivamente) em pacientes recebendo terapia anti-TNF. PACIENTES E MÉTODOS: Foram avaliados 143 pacientes reumatológicos em um estudo observacional, com artrite reumatoide, espondilite anquilosante, artrite psoriásica e outras doenças, em uso de terapia anti-TNF (adalimumabe, etanercepte e infliximabe) no período de setembro de 2007 a novembro de 2008. Foram coletados dados clínicos e demográficos, bem como uma amostra de sangue para a análise da presença de anticorpos contra os agentes infecciosos HIV (Aids), HBV e HCV (hepatites B e C, respectivamente), Treponema pallidum (sífilis) e Trypanosoma cruzii (doença de Chagas). RESULTADOS: A média de idade da população estudada foi de 45,78 ± 12,7 anos, sendo 60,1 por cento do sexo feminino e 76,9 por cento de cor branca. Treze (9 por cento) dos pacientes apresentaram pelo menos uma sorologia positiva. Nenhum dos pacientes apresentou sorologia positiva para o Trypanosoma cruzii (doença de Chagas), bem como para HIV. Somente dois (1,4 por cento) indivíduos apresentaram positividade para o Treponema pallidum (sífilis) (ELISA positivo e VDRL negativo). A frequência de anti-HBc total foi de 5 por cento (7/140), sendo que todos estes foram positivos também para anti-HBs. O HBsAg foi negativo em todos os pacientes. Quatro pacientes tiveram HCV positivo, sendo que dois deles tinham PCR negativo para o vírus e outros...

INTRODUCTION: Patients with rheumatic diseases treated with anti-tumor necrosis factor (anti-TNF) are considered to be immunosuppressed. Therefore, investigation for infectious diseases is mandatory in this population due to the high morbidity and, occasionally, mortality associated with this condition. OBJECTIVES: The objective of the present study was to evaluate the frequency of seropositivity for the following infectious agents: syphilis, Chagas' disease, acquired human immunodeficiency virus (HIV), and hepatitis B and C in patients under anti-TNF therapy. PATIENTS AND METHODS: This observational study evaluated 143 rheumatology patients with rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and others, under anti-TNF therapy (adalimumab, etanercept, and infliximab) from September 2007 to November 2008. Clinical and demographic data, as well as presence of antibodies against HIV, hepatitis B and C, syphilis, and Chagas' disease, were evaluated. RESULTS: The study population had a mean age of 45.78 ± 12.7 years; 60.1 percent were females and 76.9 percent Caucasian. Thirteen (9 percent) patients had at least one positive serology. None of the patients had antibodies to Chagas' disease and HIV. Only two (1.4 percent) individuals were positive for syphilis (positive ELISA and negative VDRL). The frequency of total anti-HBc was 5 percent (7/140), and those patients were also positive for anti-HBs. All patients were negative for AgHBs. Four patients were HCV positive: and two of them had negative virus PCR and the other two were positive, but they were stable. CONCLUSION: The frequency of seropositivity for different infectious diseases in patients under anti-TNF therapy is low. Individuals with positive serology for hepatitis C deserve close attention.

Adaptação transcultural da versão simplificada (s) do Behçet's Disease Current Activity Form (BDCAF) e comparação do desempenho das versões brasileiras dos dois instrumentos de avaliação da atividade da Doença de Behçet: BR-BDCAF e BR-BDCAF(s) / Cross-cultural adaptation of simplified version (s) of Behçet's Disease Current Activity Form (BDCAF) and comparison between two different instruments with Brazilian versions for evaluating Behçet's Disease Activity: BR-BDCAF and BR-BDCAF(s)

OBJETIVO: Um instrumento de avaliação da atividade da Doença de Behçet (DB) denominado Behçet's Disease Current Activity Form (BDCAF) foi originalmente elaborado em língua inglesa e adaptado para a língua portuguesa do Brasil na versão BR-BDCAF. Recentemente, um modelo simplificado desse protocolo (com 12 itens) foi apresentado pela Sociedade Internacional para a Doença de Behçet (International Society for Behçet's Disease, ISBD) para produzir um índice denominado BDAI (Behçet's Disease Activity Index). Por esse motivo, neste trabalho produzimos o modelo simplificado da versão brasileira, medimos sua confiabilidade e avaliamos a validade dos resultados de ambos os instrumentos, comparando seus desempenhos. MÉTODO: O modelo simplificado da versão brasileira BR-BDCAF, adaptada transculturalmente, foi denominado BR-BDCAF(s). Ambos os protocolos foram aplicados em 25 pacientes com DB. A confiabilidade do BR-BDCAF(s) foi avaliada através das reprodutibilidades intra e interobservadores pela estatística kappa. A validade e as propriedades diagnósticas sensibilidade(S), especificidade(E) e acurácia dos dois protocolos na definição de casos ativos da doença foram avaliadas pela comparação ao julgamento clínico de um reumatologista perito em DB, e os melhores pontos de corte foram estabelecidos para cada instrumento através da curva ROC (receive-operator characteristic). RESULTADOS E CONCLUSÕES: BR-BDCAF(s) apresentou boa confiabilidade nas questões sobre manifestações mucocutâneas e articulares da DB. Os melhores pontos de corte para a definição de casos ativos foram índices maiores que quatro no BR-BDCAF (S = 80,0 por cento, E = 86,7 por cento) e maiores que um no BR-BDCAF(s) (S = 70,0 por cento, E = 86,7 por cento). Suas acurácias foram semelhantes, sugerindo que ambos podem ser utilizados como instrumentos de medida de atividade da DB.

OBJECTIVE: Behçet's Disease Current Activity Form (BDCAF), an instrument for assessing activity of Behçet's Disease (BD), was originally produced in English. Its cross-cultural adaptation to Brazilian Portuguese language generated a version called BR-BDCAF. Recently, a simplified model of this protocol (with 12 items) was developed by the International Society for Behçet's Disease (ISBD) to generate an index called BDAI (Behçet's Disease Activity Index). For this reason, in this work we intended to create the simplified model of the Brazilian version, measure their reliability and evaluate the validity of the results of both instruments, comparing their performances. METHODS: The simplified version of BR-BDCAF was called BR-BDCAF(s). Both protocols were applied in 25 BD patients. Reliability of BR-BDCAF(s) was evaluated through intra- and interobserver agreement according to kappa statistic. Sensitivity (Se), specificity (Sp) and accuracy of both protocols on defining BD active cases were evaluated by comparing the rheumatologist expert clinical judgement to each protocol, and the best cut-off points were established for each instrument by the ROC curve (receive-operator characteristic). RESULTS AND CONCLUSIONS: BR-BDCAF(s) showed good reliability on items relating to mucocutaneous and articular manifestations of BD. The best cut-off points for the definition of active cases were: higher than four with BR-BDCAF (Se = 80.0 percent, Sp = 86.7 percent) and higher than one with BR-BDCAF( s) (Se = 70.0 percent, Sp = 86.7 percent). Accuracy of both protocols was similar, suggesting that both can be used as tools to assess activity of DB.

Síndrome de Behçet: à procura de evidências / Behçet’s Syndrome: looking of evidences

A síndrome de Behçet (SB) é uma afecção inflamatória multissistêmica, de acometimento vascular e de causa ainda desconhecida, basicamente caracterizada por úlceras orais e genitais recorrentes, uveíte e lesões cutâneas. A perda da visão é freqüente, resultados de ataques repetidos de inflamação. Reconhecida atualmente como um modelo singular de vasculite, a SB parece apresentar elementos de suscetibilidade genética do portador e fatores ambientados desencadeantes. O estabelecimento de critérios internacionais de diagnósticos/classificação, em 1990, e protocolos clínicos em desenvolvimento para medida da atividade da doença podem permitir a padronização das pesquisas na área. Neste artigo são revistos dados epidemiológicos, clínicos, as hipóteses correntes sobre etiogenia e fisiopatologia e dados atuais sobre as diferentes intervenções terapêuticas, considerando as drogas imunossupressoras clássicas e os novos agentes biológicos, destacando a necessidade de novas informações baseadas em evidências nesta área.