Seroprevalencia del SARS-CoV-2 en los pacientes con enfermedades inmunomediadas en tratamiento con terapias biológicas y sintéticos dirigidos / Seroprevalence of SARS-CoV-2 antibodies in patients with immune-mediated inflammatory diseases treated with biological and synthetic targeted therapies

INTRODUCCIÓN: La seroprevalencia del SARS-CoV-2 en las enfermedades inflamatorias inmunomediadas (IMID) sigue siendo fuente de controversia. OBJETIVO: Comparar la seroprevalencia de anticuerpos (Ac) anti SARS-CoV-2 en pacientes con IMID en tratamientos con fármacos antirreumáticos modificadores de la enfermedad biológicos (FAMEb) o sintéticos dirigidos (FAMEsd) frente a un grupo de personas sin IMID. MÉTODOS: Estudio de pacientes con IMID y tratamientos con FAMEb y FAMEsd y de individuos sin IMID. Mediante la técnica de inmunoensayo por quimioluminiscencia indirecta, se determinaron las serologías IgG frente al SARS-CoV-2 entre octubre/2020 y mayo/2021. RESULTADOS: Se estudiaron 1.100 sujetos, 550 pacientes con IMID y 550 personas sin IMID. Se observó una seroprevalencia de 16% (88/550) en los pacientes frente a 19,3% (106/550) en el grupo de personas sin IMID, sin significación estadística (OR 0,790 [IC 95% 0,558-1,118]). Comparando los tratamientos con FAMEb o FAMEsd, se observó una tendencia a una menor seroprevalencia con rituximab, en relación con los individuos sin IMID (OR 0,296 [IC 95% 0,0871,007]). Asimismo, se encontró menor seroprevalencia en los pacientes que además de su FAMEb recibían tratamiento con metotrexato, en comparación con el grupo de personas sin IMID (OR 0,432 [IC 95% 0,223-0,835]). CONCLUSIONES: Las IMID en tratamiento con FAMEb o FAMEsd no influyen en la seroprevalencia frente al SARS-CoV-2 de los pacientes. El tratamiento concomitante con metotrexato disminuye de forma significativa la seroprevalencia en estos pacientes.

BACKGROUND: The seroprevalence of SARS-CoV-2 in immunemediated inflammatory diseases (IMID) remains controversial. AIM: To compare the seroprevalence of antibodies (Ab) to SARS-CoV-2 in patients with IMID receiving treatment with biological diseasemodifying antirheumatic drugs (bDMARD) or targeted synthetic (tsDMARD) versus a group of people without IMID. METHODS: Study of patients with IMID and treatments with bDMARD and tsDMARD and individuals without IMID. IgG serology against SARS-CoV-2 was measured using the two-step sandwich immunoassay technique by indirect chemiluminescence between October 2020 and May 2021. RESULTS: A total of 1100 subjects were studied, 550 patients with IMID and 550 persons without IMID. A seroprevalence of 16% (88/550) was observed in patients versus 19.3% (106/550) in the group of people without IMID, without statistical significance (OR 0.790 [95% CI 0.558-1.118]). Comparing the treatments with bD- MARD or tsDMARD, there was a tendency to lower seroprevalence with rituximab, in relation to individuals without IMID (OR 0.296 [95% CI 0.087-1.007]). In addition, lower seroprevalence was found in patients who received methotrexate treatment in addition to their bDMARD, compared to the group of individuals without IMID (OR 0.432 [95% CI 0.223-0.835]). CONCLUSIONS: IMIDs in treatment with bDMARDs or tsDMARDs do not influence the seroprevalence against SARS-CoV-2 in patients. Concomitant treatment with methotrexate significantly decreased seroprevalence in these patients.

Traditional Chinese medicine therapy for rheumatoid arthritis: a review / 中国中药杂志

Rheumatoid arthritis(RA) is an autoimmune disease that seriously affects the physical and mental health of patients, but its pathogenesis is still unclear. At present, clinical treatment drugs include conventional synthetic disease modifing anti-rheumatic drugs(csDMARDs), nonsteroid anti-inflammtory drugs(NSAIDs), hormones, small molecule targeted drugs, biological agents, etc. These drugs can relieve the clinical symptoms of most patients with RA to a certain extent, but there are still many limitations, such as drug adverse reactions and individual differences in drug efficacy. Therefore, the research on drug treatment targets and the development of low-toxicity drugs helps further improve the precise prevention, diagnosis, and treatment of RA. There is an urgent need for efficient and low-toxic treatments to delay the clinical progress of RA. As a treasure of Chinese culture, traditional Chinese medicine(TCM) is widely used as an alternative therapy in the treatment of various diseases, and has a significant clinical efficacy. TCM therapy(including monomer traditional Chinese medicine, classical compounds, and non-drug therapies) has a significant curative effect on RA. Based on the literature research in recent years, this paper reviewed the clinical and mechanism research of TCM therapy in the treatment of RA, and provided more in-depth thinking for the wide application of TCM therapy in clinical practice.

Continuation, reduction, or withdrawal of tofacitinib in patients with rheumatoid arthritis achieving sustained disease control: a multicenter, open-label, randomized controlled trial / 中华医学杂志(英文版)

BACKGROUND@#Rheumatoid arthritis (RA), a chronic systemic autoimmune disease, is characterized by synovitis and progressive damage to the bone and cartilage of the joints, leading to disability and reduced quality of life. This study was a randomized clinical trial comparing the outcomes between withdrawal and dose reduction of tofacitinib in patients with RA who achieved sustained disease control.@*METHODS@#The study was designed as a multicenter, open-label, randomized controlled trial. Eligible patients who were taking tofacitinib (5 mg twice daily) and had achieved sustained RA remission or low disease activity (disease activity score in 28 joints [DAS28] ≤3.2) for at least 3 months were enrolled at six centers in Shanghai, China. Patients were randomly assigned (1:1:1) to one of three treatment groups: continuation of tofacitinib (5 mg twice daily); reduction in tofacitinib dose (5 mg daily); and withdrawal of tofacitinib. Efficacy and safety were assessed up to 6 months.@*RESULTS@#Overall, 122 eligible patients were enrolled, with 41 in the continuation group, 42 in the dose-reduction group, and 39 in the withdrawal group. After 6 months, the percentage of patients with a DAS28-erythrocyte sedimentation rate (ESR) of <3.2 was significantly lower in the withdrawal group than that in the reduction and continuation groups (20.5%, 64.3%, and 95.1%, respectively; P  < 0.0001 for both comparisons). The average flare-free time was 5.8 months for the continuation group, 4.7 months for the dose reduction group, and 2.4 months for the withdrawal group.@*CONCLUSION@#Withdrawal of tofacitinib in patients with RA with stable disease control resulted in a rapid and significant loss of efficacy, while standard or reduced doses of tofacitinib maintained a favorable state.@*TRIAL REGISTRATION@#Chictr.org, ChiCTR2000039799.

Effectiveness of tofacitinib combined with iguratimod in the treatment of difficult-to-treat moderate-to-severe rheumatoid arthritis / 北京大学学报(医学版)

OBJECTIVE@#To investigate the efficacy and safety of iguratimod combined with tofacitinib in patients with difficult-to-treat moderate-to-severe rheumatoid arthritis (RA).@*METHODS@#In this prospective clinical study, 30 patients with difficult-to-treat moderate-to-severe RA who attended the Department of Rheumatology and Immunology of Shanxi Province Fenyang Hospital from September 2021 to June 2022 were selected. Twenty-three patients enrollment had been treated with 2 or more conventional synthetic disease modifying anti-rheumatic drugs (DMARDs) for more than 6 months. At least, methotrexate or leflunomide was included. Seven patients were treated with conventional synthetic DMARDs combined with tumor necrosis factor antagonists. Because all the patients had not reached the target of treatment, the combination treatment regimen of DMARDs was changed to iguratimod and tofacitinib. The observation period was 12 weeks. Clinical data were collected before and after treatment. At the end of 4 weeks, 8 weeks and 12 weeks, the clinical data were collected such as swollen joints count (SJC), tender joints count (TJC), time of morning stiffness, clinical disease activity index (CDAI), health status assessment questionnaire (HAQ), and 28-joint disease activity score (DAS28) were included. We collected laboratory indicators, recorded the patient's medication, and observed some changes to see if any adverse drug reactions occurred during the treatment.@*RESULTS@#There were significant differences in erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), platelet (PLT), SJC, TJC, DAS28 based on ESR(DAS28-ESR), time of morning stiffness, HAQ, CDAI, and anti-cyclic citrullinated peptide antibody before and after treatment. The differences had statistical significance (P < 0.05). There was no statistical differences in globulin before and after treatment (P>0.05). During the treatment of iguratimod combined with tofacitinib, there was no serious adverse reactions such as leukopenia, significant elevation of liver enzymes, allergy or thromboemblolic events that occurred in all the patients.@*CONCLUSION@#Iguratimod combined with tofacitinib in the treatment of difficult-to-treat moderate-to-severe RA may have efficacy. The machanism was improving the patients' recent clinical symptoms by reducing inflammatory indexes. This combination treatment regimen with iguratimod and tofacitinib has a good safety profile.

Expert recommendations for the chronic disease management of rheumatic arthritis / 中华内科杂志

Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease that poses a major healthcare challenge. In China, approximately 5 million patients are reported to have RA. Notably, Chinese patients with RA often experience a prolonged disease course and increased disease activity, leading to a substantial disease burden. The Chronic Disease Management Group of the Special Committee on Rheumatology and Immunology of Cross-Straits Medicine Exchange Association has advocated for an all-encompassing, continuous, and proactive scientific management approach for RA. This initiative has culminated in the formulation of the "Expert Recommendations for the Chronic Disease Management of Rheumatoid Arthritis", a comprehensive guideline developed through extensive consultations and consideration of the unique characteristics of RA. We have outlined 16 expert recommendations, addressing 10 key aspects central to RA management. We aim to enhance treatment outcomes for patients, streamline the distribution of medical resources, and reduce treatment-related burden on society, families, and individuals affected by this condition.

Infección por virus de epstein barr y debut de lupus eritematoso sistémico (LES) en un adolescente / Epstein barr virus infection and systemic lupus erythematosus (SLE) debut in an adolescent / Infecção pelo vírus Epstein Barr e início de lúpus eritematoso sistêmico (LES) em adolescente

Introducción: El lupus eritematoso sistémico (LES), prototipo de enfermedad autoinmune, cursa con empujes y remisiones. Dada la diversidad de presentaciones posibles, su diagnóstico y tratamiento son un reto para el clínico, y se requiere tener un alto índice de sospecha. Objetivo: presentar el caso clínico de un adolescente que debuta con LES a forma de anemia hemolítica, probablemente gatillado por infección por virus de Epstein Barr. Caso clínico: Varón de 14 años, sin antecedentes a destacar. Consulta por fiebre de 7 días de evolución de hasta 39º C, odinofagia, astenia y adinamia. Al examen físico se constata palidez cutáneo mucosa, ictericia, adenopatías cervicales y hepatoesplenomegalia. El laboratorio muestra anemia severa regenerativa con aumento de las bilirrubinas a expensas de la indirecta sin hepatitis. Prueba de Coombs positiva. Anticuerpos específicos para Epstein Barr positivos, con lo que se diagnostica anemia hemolítica secundaria a mononucleosis y se inicia tratamiento corticoideo. En la evolución agrega eritema malar y limitación en flexión de codos y rodillas. Se reciben anticuerpos antinucleares y anti ADN nativo positivos con hipocomplementemia severa. Con diagnóstico de LES se inicia hidroxicloroquina y azatioprina, manteniéndose la prednisona. Conclusiones: Muchos virus (hepatitis C, Parvovirus B19, Epstein Barr y Citomegalovirus) se han descrito como posibles inductores o simuladores de LES. Es necesario mantener un alto índice de sospecha para realizar un diagnóstico oportuno y tratamiento precoz.

Introduction: Systemic lupus erythematosus (SLE), prototype of autoimmune disease, progresses with flares and remissions. Given the diversity of possible presentations, its diagnosis and treatment are a challenge for the clinician, and a high index of suspicion is required. Objective: To present the clinical case of an adolescent who debuted with SLE in the form of hemolytic anemia, probably triggered by Epstein Barr virus infection. Clinical case: 14 - year - old male, with no history to highlight. Consultation for fever of 7 days of evolution of up to 39º C, odynophagia, asthenia and adynamia. Physical examination revealed mucous skin pallor, jaundice, cervical lymphadenopathy, and hepatosplenomegaly. The laboratory shows severe regenerative anemia with increased bilirubin at the expense of indirect without hepatitis. Positive Coombs test. Specific antibodies for Epstein Barr were positive, with which hemolytic anemia secondary to mononucleosis was diagnosed and corticosteroid treatment was started. In the evolution, it adds malar erythema and limitation in flexion of the elbows and knees. Positive antinuclear and anti-native DNA antibodies are received with severe hypocomplementemia. With a diagnosis of SLE, hydroxychloroquine and azathioprine were started, maintaining prednisone. Conclusions: Many viruses (hepatitis C, Parvovirus B19, Epstein Barr and Cytomegalovirus) have been described as possible inducers or mimics of SLE. It is necessary to maintain a high index of suspicion for timely diagnosis and early treatment.

Introdução: O lúpus eritematoso sistêmico (LES), protótipo de doença autoimune, evolui com impulsos e remissões. Dada a diversidade de apresentações possíveis, seu diagnóstico e tratamento são um desafio para o clínico, sendo necessário um alto índice de suspeição. Objetivo: apresentar o caso clínico de uma adolescente que iniciou com LES na forma de anemia hemolítica, provavelmente desencadeada por infecção pelo vírus Epstein Barr. Caso clínico: Homem de 14 anos, sem antecedentes a destacar. Consulta por febre de 7 dias de evolução de até 39º C, odinofagia, astenia e adinamia. O exame físico revelou palidez cutânea mucosa, icterícia, linfadenopatia cervical e hepatoesplenomegalia. O laboratório mostra anemia regenerativa grave com aumento da bilirrubina em detrimento da indireta sem hepatite. Teste de Coombs positivo. Anticorpos específicos para Epstein Barr foram positivos, com o qual foi diagnosticada anemia hemolítica secundária à mononucleose e iniciado tratamento com corticosteróides. Na evolução, acrescenta eritema malar e limitação na flexão dos cotovelos e joelhos. Anticorpos antinucleares e anti-DNA nativos positivos são recebidos com hipocomplementemia grave. Com diagnóstico de LES, iniciou-se hidroxicloroquina e azatioprina, mantendo-se prednisona. Conclusões: Muitos vírus (hepatite C, Parvovírus B19, Epstein Barr e Citomegalovírus) têm sido descritos como possíveis indutores ou mimetizadores do LES. É necessário manter um alto índice de suspeição para diagnóstico oportuno e tratamento precoce.

Risk of tuberculosis in patients with rheumatoid arthritis treated with biological and targeted drugs: meta-analysis of randomized clinical trials / 中华医学杂志(英文版)

BACKGROUND@#Concerns exist regarding the potential development of tuberculosis in patients with rheumatoid arthritis (RA) treated with biological and targeted drugs. We assessed systematically whether biological therapy increased the risk of tuberculosis in patients with RA by meta-analysis of randomized controlled trials (RCTs).@*METHODS@#A systematic literature search was conducted in PubMed, Embase, the Cochrane Library, and China Biology Medicine disc for RCTs evaluating biological therapy in patients with RA from inception through August 2021. Traditional meta-analysis and network meta-analysis were performed to compare the risk of tuberculosis for each biologics class in patients with RA. Peto odds ratio (Peto OR) and its 95% confidence interval (CI) were calculated as the primary effect measure.@*RESULTS@#In total, 39 studies with 20,354 patients were included in this meta-analysis, and 82 patients developed tuberculosis. The risk of tuberculosis was increased in patients treated with biologics compared with non-biologics (Peto OR: 3.86, 95% CI: 2.36-6.32, P < 0.001). Also, tumor necrosis factor-α (TNF-α) inhibitors had a higher probability of developing tuberculosis than placebo (Peto OR: 3.98, 95% CI: 2.30-6.88, P < 0.001). However, network meta-analysis demonstrated that there was no significant difference in the risk of tuberculosis for each biologics class in patients with RA. Noticeably, tuberculosis was significantly more common in patients treated with a high dose compared with patients receiving a low dose of tofacitinib (Peto OR: 7.39, 95% CI: 2.00-27.31, P = 0.003).@*CONCLUSION@#This meta-analysis demonstrates the evidence of an elevated risk of tuberculosis in patients with RA treated with TNF-α inhibitors, and a dose-dependent elevated risk of tuberculosis in patients treated with tofacitinib.

Perfil clínico e epidemiológico e comorbidades dos pacientes com artrite reumatoide atendidos no centro de especialidades médicas do centro universitário do Pará / Clinical and epidemiological and comorbidities of patients with rheumatoid arthritis assisted at the medical specialties center of Centro Universitário do Pará

Objetivos: Descrever as características clínico e epidemiológicas e a prevalência das comorbidades que acometem os pacientes com artrite reumatóide (AR) atendidos no ambulatório de reumatologia do Centro de Especialidades Médicas do Cesupa (CEMEC). Métodos: Estudo descritivo, observacional e retrospectivo realizado por meio da coleta de dados de prontuários médicos, no período de janeiro a novembro de 2020, de pacientes com artrite reumatoide, atendidos no Centro de Especialidades Médicas do Cesupa no período de 2012 a 2020. Resultados: Foram analisados 122 prontuários. A maioria dos pacientes foi do sexo feminino (88,52%). A raça predominante foi a não branca (90,88%) e a idade média dos participantes foi 54,09 anos (DP± 11,33). A maioria dos pacientes apresentavam fatores reumatoides positivo (56,55%). O tempo médio de doença foi de 9,7 anos (±8,57). As principais comorbidades não infecciosas encontradas foram: hipertensão arterial (40,16%), osteoporose (23,77%), dislipidemia (19,67%), diabetes (12,29%), obesidade (8,19%), depressão (4,09%), neoplasias (2,45%) e osteopenia (1,63%). Os medicamentos utilizados foram metotrexato (59,83%), prednisona (55,73%), leflunomida (36,06%), tocilizumabe (7,37%), anti-TNF (7,37%), anti-inflamatórios não hormonais (6,55%), tofacitinibe (2,45%), abatacepte (2,45%) e rituximabe (0%). Conclusão: As principais comorbidades que atingiram estes pacientes foram a hipertensão, osteoporose e dislipidemia. Assim, verifica-se a necessidade do controle de fatores de risco modificáveis dessas comorbidades assim como prezar pelo uso de doses baixas e pelo menor tempo possível, a fim de, apenas enquanto as drogas modificadoras de doença reumática (DMARDs) não estão fazendo efeito, reduzir a prevalência dessas comorbidades nestes pacientes.

Objectives: To describe the clinical and epidemiological characteristics and the prevalence of the main non ­ infectious comorbidities that affect patients with rheumatoid arthritis treated at the rheumatology outpatient clinic of the Centro de Especialidades Médicas do Cesupa (CEMEC). Methods: This is a descriptive, observational and retrospective study carried out by collecting data from medical records, from January to November 2020, of patients with rheumatoid arthritis, treated a Centro de Especialidades Médicas from 2012 to 2020. Results: In total, 122 medical records were analyzed, most of which corresponded to female patients (88.52%). The predominant race was non-white (90.88%) and the mean age of the participants was 54.09 years, with a standard deviation of 11.33 years. Regarding the rheumatoid factor, most of the sample is positive (56.55%). The mean disease duration was 9.7 years, with a standard deviation of 8.57 years. The main non-infectious comorbidities found were: arterial hypertension (40.16%), osteoporosis (23.77%), dyslipidemia (19.67%), diabetes (12.29%), obesity (8.19%) depression (4,09%), neoplasms (2.45%) and osteopenia (1.63%). The drugs used were methotrexate (59.83%), prednisone (55.73%), leflunomide (36.06%), tocilizumab (7.37%), anti-TNF (7.37%), non-steroidal anti-inflammatories. hormonal agents (6.55%), tofacitinib (2.45%), abatacept (2.45%) and rituximab (0%). Conclusion: The main comorbidities that affected these patients were hypertension, osteoporosis and dyslipidemia; and the most used drugs were prednisone, methotrexate and leflunomide, which are also related to the emergence of these pathologies. Thus, there is a need to encourage the practice of physical activity, as well as to value the use of low doses of corticosteroids, only while disease-modifying anti-rheumatic drugs (DMARDs) are ineffective, in order to reduce the prevalence of these Comorbidities in these patient

Chinese registry of rheumatoid arthritis: IV. Correlation and consistency of rheumatoid arthritis disease activity indices in China / 中华医学杂志(英文版)

BACKGROUND@#Disease activity indices (DAIs) including disease activity score 28 (DAS28), simplified disease activity index (SDAI), and clinical disease activity index (CDAI) have been widely used in clinical practice and research studies of rheumatoid arthritis (RA). The objective of our study was to evaluate the correlation and concordance among different DAIs in Chinese patients with RA.@*METHODS@#A cross-sectional study, including patients enrolled in the Chinese registry of rheumatoid arthritis from November 2016 to August 2018, was conducted. The correlations were evaluated using Spearman correlation coefficient and concordance with Bland-Altman plots, quadratic weighted kappa, and discordance rates in the crosstab. For other indices, the optimal cutoff points corresponding to SDAI remission were explored through receiver operating characteristic curve analysis.@*RESULTS@#A total of 30,501 patients were included, of whom 80.46% were women. Most individuals were with moderate disease activity or high disease activity. High correlations among DAS28-erythrocyte sedimentation rate (ESR) and DAS28-C-reactive protein (CRP), SDAI and CDAI were observed. Similarly, the weighted kappa value among the indices was high. In Bland-Altman plots, a positive difference between DAS28-ESR and DAS28-CRP was observed, with an absolute difference of >1.2 in 3079 (10.09%) patients. In crosstab, approximately 30% of the patients were classified into different groups. Concordance values between SDAI remission and the optimal cutoff points of DAS28-ESR, DAS28-CRP, and CDAI were 3.06, 2.37, and 3.20, respectively.@*CONCLUSIONS@#Although DAIs had high correlations and weighted kappa values, the discordance between DAIs was significant in Chinese patients with RA. The four DAIs are not interchangeable.

A double-blind, double-dummy, randomized controlled, multicenter trial of 99Tc-methylene diphosphonate in patients with moderate to severe rheumatoid arthritis / 中华医学杂志(英文版)

BACKGROUND@#Clinical observational studies revealed that 99Tc-methylene diphosphonate (99Tc-MDP) could reduce joint pain and swollenness in rheumatoid arthritis (RA) patients. This multicenter, randomized, double-blind, double-dummy study aimed to evaluate the effects of 99Tc-MDP plus methotrexate (MTX) vs. MTX alone or 99Tc-MDP alone on disease activity and structural damage in MTX-naïve Chinese patients with moderate to severe RA.@*METHODS@#Eligible patients with moderate to severely active RA were randomized to receive 99Tc-MDP plus MTX (n = 59) vs. MTX (n = 59) alone or 99Tc-MDP (n = 59) alone for 48 weeks from six study sites across four provinces in China. The primary outcomes were the American College of Rheumatology 20% improvement (ACR20) response rates at week 24 and changes in modified total Sharp score at week 48.@*RESULTS@#At week 24, the proportion of participants achieving ACR20 was significantly higher in the MTX + 99Tc-MDP combination group (69.5%) than that in the MTX group (50.8%) or 99Tc-MDP group (47.5%) (P = 0.03 for MTX + 99Tc-MDP vs. MTX, and MTX + 99Tc-MDP vs.99Tc-MDP, respectively). The participants in the MTX + 99Tc-MDP group and the 99Tc-MDP group had significantly less important radiographic progression than the participants in the MTX group over the 48 weeks (MTX + 99Tc-MDP vs. MTX: P = 0.03, 99Tc-MDP vs. MTX: P = 0.03, respectively). There was no significant difference in terms of adverse events (AEs) among the groups. No serious AEs were observed.@*CONCLUSIONS@#This study demonstrated that the combination of 99Tc-MDP with MTX inhibited structural damage and improved disease activity in RA patients compared with MTX and 99Tc-MDP monotherapies, without increasing the rate of AEs. Additional clinical studies of 99Tc-MDP therapy in patients with RA are warranted.@*TRIAL REGISTRATION@#Chictr.org, ChiCTR-IPR-14005684; http://www.chictr.org.cn/showproj.aspx?proj=10088.

Drug prices in Latin American countries: the case of rheumatoid arthritis Biosimilars

Abstract Background: The objective of this paper is to analyze the prices of biological drugs in the treatment of Rheumatoid Arthritis (RA) in three Latin American countries (Brazil, Colombia and Mexico), as well as in Spain and the United States of America (US), from the point of market entry of biosimilars. Methods: We analyzed products authorized for commercialization in the last 20 years, in Brazil, Colombia, and Mexico, comparing them to the United States of America (USA) and Spain. For this analysis, we sought the prices and registries of drugs marketed between 1999 and October 1, 2019, in the regulatory agencies' databases. The pricing between countries was based on purchasing power parity (PPP). Results: The US authorized the commercialization of 13 distinct biologicals and four biosimilars in the period. Spain and Brazil marketed 14 biopharmaceuticals for RA, ten original, four biosimilars. Colombia and Mexico have authorized three biosimilars in addition to the ten biological ones. For biological drug prices, the US is the most expensive country. Spain's price behavior seems intermediate when compared to the three LA countries. Brazil has the highest LA prices, followed by Mexico and Colombia, which has the lowest prices. Spain has the lowest values in PPP, compared to LA countries, while the US has the highest prices. Conclusions: The economic effort that LA countries make to access these medicines is much higher than the US and Spain. The use of the PPP ensured a better understanding of the actual access to these inputs in the countries analyzed.(AU)

Análise do perfil clínico e epidemiológico de pacientes com artrite psoriásica em ambulatório de reumatologia na Região Amazônica / Clinical and epidemiological profile analysis of patients with psoriatic arthritis in a rheumatology clinic in the Amazon Region

Objetivo: Conhecer o perfil clínico e epidemiológico de pacien- tes portadores de artrite psoriásica de uma região brasileira. Método: Pesquisa observacional, transversal, epidemiológica e documental, baseada na coleta de dados obtidos a partir da análise de 53 prontuários de pacientes cadastrados do Ambu- latório de Reumatologia da Universidade do Estado do Pará, na Região Amazônica. Resultados: Houve predominância do padrão do tipo poliartrite simétrica, sem distinção entre os sexos, com a presença de manifestações extra-articulares, pso- ríase em placas, em uso de metotrexato em doses médias. Con- clusão: Apesar da etiopatogenia da doença ser dependente de fatores genéticos, ambientais e imunológicos e da população amazônica ser muito particular, de uma miscigenação entre eu- ropeus, ameríndios e negros, o perfil clínico e epidemiológicos dos pacientes do Ambulatório de Reumatologia da Universidade do Estado do Pará é semelhante ao das literaturas nacional e internacional.

Objective: To know the clinical and epidemiologic profile of pso- riatic arthritis patients of a Brazilian region. Method: This is an observational, cross-sectional, epidemiological, and documental study, based on the data obtained from the analysis of the medi- cal records of 53 patients registered on the Rheumatology Cli- nic of the Universidade do Estado do Pará, in the Amazon area. Results: There was a predominance of the symmetrical polyar- ticular pattern, with no sexual distinction, extra articular invol- vement, plaque psoriasis, and treatment withn methotrexate, in medium doses. Conclusion: Despite the etiopathogenesis being dependent on genetic, environmental, and immunological fac- tors, and the population of the Amazon being a mix of Europeans, Amerindians, and black people, the clinical and epidemiological profile of the patients of the Rheumatology clinic of the Univer- sidade do Estado do Pará is similar to the ones described on the national and international literature.

Risk factors for losing hepatitis B virus surface antibody in patients with HBV surface antigen negative/surface antibody positive serostatus receiving biologic disease-modifying anti-rheumatic drugs: a nested case-control study

Abstract Background: Hepatitis B virus (HBV) reactivation consequent to immunosuppressive therapy is an increasingly prevalent problem with serious clinical implications. Treatment with biologic agents conduces to the loss of protective antibody to HBV surface antigen (anti-HBs), which significantly increases the risk of HBV reactivation. Hence, we investigated the risk factors for losing anti-HBs in patients with rheumatic diseases and HBV surface antigen negative/anti-HBs positive (HBsAg-/anti-HBs+) serostatus during treatment with biologic disease-modifying anti-rheumatic drugs (DMARDs). Methods: Using a nested case-control design, we prospectively enrolled patients with rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis/psoriasis, or juvenile idiopathic arthritis, who were treated with biologic DMARDs at Changhua Christian Hospital, Taiwan, from January 2013 to June 2019 and had HBsAg-/anti-HBs+ serostatus; the analytic sample excluded all patients with HBsAg+ or anti-HBs- serostatus. Anti-HBs titers were monitored 6-monthly and cases were defined as anti-HBs < 10 mIU/ml during follow-up. Cases were matched one- to-all with controls with anti-HBs ≥ 10 mIU/ml on the same ascertainment date and equivalent durations of biologic DMARDs treatment (control patients could be resampled and could also become cases during follow-up). Between-group characteristics were compared and risk factors for anti-HBs loss were investigated by conditional logistic regression analyses. Results: Among 294 eligible patients, 23 cases were matched with 311 controls. The incidence of anti-HBs loss was ∼ 2.7%/person-year during biologic DMARDs treatment. Besides lower baseline anti-HBs titer (risk ratio 0.93, 95% CI 0.89-0.97), cases were significantly more likely than controls to have diabetes mellitus (risk ratio 4.76, 95% CI 1.48-15.30) and chronic kidney disease (risk ratio 14.00, 95% CI 2.22-88.23) in univariate analysis. Risk factors remaining significantly associated with anti-HBs loss in multivariate analysis were lower baseline anti-HBs titer (adjusted risk ratio 0.93, 95% CI 0.88-0.97) and chronic kidney disease (adjusted risk ratio 45.68, 95% CI 2.39-871.5). Conclusions: Besides lower baseline anti-HBs titer, chronic kidney disease also strongly predicts future anti-HBs negativity in patients with HBsAg-/anti-HBs+ serostatus who receive biologic DMARDs to treat rheumatic diseases. Patients with low anti-HBs titer (≤ 100 mIU/ml) and/or chronic kidney disease should be monitored during biologic DMARDs therapy, to enable timely prophylaxis to preempt potential HBV reactivation.

Meta-analysis of efficacy and safety of sinomenine combined with methotrexate in treatment of rheumatoid arthritis / 中国中药杂志

To systemically evaluate the efficacy and safety of sinomenine combined with methotrexate(SIN+MTX) in the treatment of rheumatoid arthritis(RA). Literature databases of Wanfang, CNKI, VIP, SinoMed, PubMed, Cochrane Library and Web of Science were retrieved comprehensively for relevant clinical trials. The literature retrieval time was from database establishment to February 4, 2020. The quality of literatures was assessed by the Cochrane Evaluation Handbook 5.1.0, and qualified literature was reviewed and analyzed by using the RevMan 5.3 statistical software. Twenty randomized controlled trials met the inclusion criteria, and were enrolled in the Meta-analysis. The results showed that SIN+MTX remarkably reduced DAS28(MD=-0.85, 95%CI[-1.03,-0.67], P<0.000 01), and improved total efficiency(P<0.000 01). SIN+MTX could inhibit swollen joint count(MD=-1.19, 95%CI[-1.75,-0.63], P<0.000 1), tender joint count(MD=-1.58, 95%CI[-2.89,-0.28], P=0.02) and reduce morning stiffness time(MD=-8.44, 95%CI[-11.82,-5.07], P<0.000 01) compared with control group. The results showed that SIN+MTX was equal to control group in grip strength(SMD=0.20,95%CI[-1.11,1.51],P=0.77). SIN+MTX remarkably alleviated the erythrocyte sedimentation rate(MD=-9.87, 95%CI[-14.52,-5.22], P<0.000 1), C-reactive protein(SMD=-0.30, 95%CI[-0.51,-0.09], P=0.005), and rheumatoid factor(MD=-11.23,95%CI[-13.81,-8.65],P<0.000 01). The frequency of adverse reactions were reduced compared with that in the control group(P<0.000 01). Current clinical studies demonstrate that the efficacy and safety of SIN+MTX in the treatment of RA were superior to control group. However, due to the low quality and quantity of the included studies, high-quality randomized controlled trials are necessary to support the clinical evidences.

Informe diário de evidências COVID-19: busca referente aos dias 1, 2 e 3 de agosto de 2020 / COVID-19 daily evidence report: search related to August 1, 2 and 3, 2020

O Informe Diário de Evidências é uma produção do Ministério da Saúde que tem como objetivo acompanhar diariamente as publicações científicas sobre tratamento farmacológico e vacinas para a COVID-19. Dessa forma, são realizadas buscas estruturadas em bases de dados biomédicas, referentes ao dia anterior desse informe. Não são incluídos estudos pré-clínicos (in vitro, in vivo, in silico). A frequência dos estudos é demonstrada de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, coortes, entre outros). Para cada estudo é apresentado um resumo com avaliação da qualidade metodológica. Essa avaliação tem por finalidade identificar o grau de certeza/confiança ou o risco de viés de cada estudo. Para tal, são utilizadas ferramentas já validadas e consagradas na literatura científica, na área de saúde baseada em evidências. Cabe ressaltar que o documento tem caráter informativo e não representa uma recomendação oficial do Ministério da Saúde sobre a temática. Foram encontrados 16 artigos.

Informe diário de evidências COVID-19: busca realizada em 4 de agosto de 2020 / COVID-19 daily evidence report: search conducted on August 4, 2020

O Informe Diário de Evidências é uma produção do Ministério da Saúde que tem como objetivo acompanhar diariamente as publicações científicas sobre tratamento farmacológico e vacinas para a COVID-19. Dessa forma, são realizadas buscas estruturadas em bases de dados biomédicas, referentes ao dia anterior desse informe. Não são incluídos estudos pré-clínicos (in vitro, in vivo, in silico). A frequência dos estudos é demonstrada de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, coortes, entre outros). Para cada estudo é apresentado um resumo com avaliação da qualidade metodológica. Essa avaliação tem por finalidade identificar o grau de certeza/confiança ou o risco de viés de cada estudo. Para tal, são utilizadas ferramentas já validadas e consagradas na literatura científica, na área de saúde baseada em evidências. Cabe ressaltar que o documento tem caráter informativo e não representa uma recomendação oficial do Ministério da Saúde sobre a temática. Foram encontrados 16 artigos e 13 protocolos.

Síndrome de DRESS inducido por sulfasalazina. ¿Consideramos esta reacción adversa grave al indicar el fármaco? Caso clínico

DRESS syndrome (Drug Reaction with Eosinophilia and Systemic Symptoms) is a severe, rare and potentially lethal idiosyncratic condition associated with the use of some drugs. Given its broad spectrum of presentation, clinical suspicion is essential for management, since it requires the immediate withdrawal of the culprit drug, support measures and the use of corticosteroids as the first line of treatment. We report a 24-year-old woman with a diagnosis of ulcerative colitis with joint involvement despite the use of infliximab, who presented symptoms, signs and laboratory compatible with DRESS syndrome on the third week after indicating sulfasalazine for her baseline disease.

Informe diário de evidências COVID-19: busca realizada em 1 de julho de 2020 / COVID-19 daily evidence report: search conducted on July 1, 2020

O Informe Diário de Evidências é uma produção do Ministério da Saúde que tem como objetivo acompanhar diariamente as publicações científicas sobre tratamento farmacológico e vacinas para a COVID-19. Dessa forma, são realizadas buscas estruturadas em bases de dados biomédicas, referente ao dia anterior desse informe. Não são incluídos estudos pré-clínicos (in vitro, in vivo, in silico). A frequência dos estudos é demonstrada de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, coortes, entre outros). Para cada estudo é apresentado um resumo com avaliação da qualidade metodológica. Essa avaliação tem por finalidade identificar o grau de certeza/confiança ou o risco de viés de cada estudo. Para tal, são utilizadas ferramentas já validadas e consagradas na literatura científica, na área de saúde baseada em evidências. Cabe ressaltar que o documento tem caráter informativo e não representa uma recomendação oficial do Ministério da Saúde sobre a temática. Foram encontrados 14 artigos e 6 protocolos.