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1.
Arthritis Rheumatol ; 2019 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-31237427

RESUMO

OBJECTIVE: To compare the efficacy of infliximab (IFX) versus adalimumab (ADA) as first biologic drug in a large series of patients with refractory uveitis due to Behçet's disease (BD) for 1-year period. METHODS: Open-label multicenter study of IFX or ADA-treated patients with BD-uveitis refractory to conventional non-biologic treatment. IFX or ADA were chosen as first biologic treatment based on physician and patient agreement. Dosing schedule was: IFX: 3-5 mg/kg i.v. at 0, 2 and 6 weeks and every 4-8 weeks thereafter, and ADA: 40 mg/s.c./every other week without loading dose. Comparison between patients treated with IFX and patients treated with ADA was performed. RESULTS: 177 patients (316 affected eyes) were included. IFX was used in 103 and ADA in 74 cases. No significant differences at baseline were observed between IFX vs ADA groups regarding main demographic features, previous therapy and ocular severity. After one year of therapy, we observed an improvement in all ocular parameters in both groups. However, ADA therapy yielded better outcome in some parameters that in some cases yielded statistically significant differences: anterior chamber inflammation (78.18% in IFX-treated vs 92.31%in ADA-treated; p=0.06), vitritis (78.95% vs 93.33%; p=0.04), retinal vasculitis (97% vs 95%; p=0.28), macular thickness (264.89±59.74 vs 250.62±36.85; p=0.15), best-corrected visual acuity (0.67±0.34 vs 0.81±0.26; p=0.001), and drug retention (84.95% vs 95.24%; p=0.042). CONCLUSION: Although IFX and ADA yields efficacy refractory BD uveitis, ADA appears to be associated with better outcome than IFX after one-year follow-up. This article is protected by copyright. All rights reserved.

2.
Clin Exp Rheumatol ; 2019 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-30789151

RESUMO

OBJECTIVES: Cardiovascular (CV) disease is one of the main causes of morbi-mortality in spondyloarthritis (SpA), partially explained by traditional CV risk factors. Information on lipoprotein(a) [Lp(a)], a non-conventional risk factor, in SpA is scarce. In this study we assessed the prevalence of hyperlipoproteinaemia(a) in SpA patients and analysed the possible related factors. METHODS: A baseline analysis was made of ankylosing spondylitis (AS) and psoriatic arthritis (PsA) patients and controls included in the CARMA project (CARdiovascular in RheuMAtology), a 10-year prospective study evaluating the risk of CV events in chronic inflammatory rheumatic diseases. A multivariate logistic regression model was performed using hyperlipoproteinaemia(a) (Lp(a) >50 mg/dl) as a dependent variable and adjusting for confounding factors. RESULTS: 19.2% (95% CI: 16.80-22.05) of the SpA patients [20.7% (95% CI: 16.91-24.82) of those with AS and 17.7% (95% CI: 14.15-21.75) of those with PsA] and 16.7% (95% CI: 13.23-20.86) of the controls had hyperlipoproteinaemia(a) (p=0.326). Adjusting for age and sex, SpA patients were more likely to have hyperlipoproteinaemia(a) than controls (OR: 1.43, 95%CI: 1.00-2.04; p=0.05), especially those with AS (OR: 1.81, 95%CI: 1.18-2.77; p=0.007). In the adjusted model, apolipoprotein B in all patients, non-steroidal anti-inflammatory drugs in AS, and female sex in PsA, were associated with hyperlipoproteinaemia(a). No disease-specific factors associated with hyperlipoproteinaemia(a) were identified. CONCLUSIONS: SpA patients show a moderately increased risk of hyperlipoproteinaemia(a) compared to controls, especially those with AS. Lp(a) determination may be of interest to improve the CV risk assessment in SpA patients.

3.
Reumatol Clin ; 2018 Mar 09.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-29530760

RESUMO

An acute inflammatory arthritis of unknown cause has been described in beekeepers in relation to their work with the hives. We present the case of a beekeeper who, after a bee sting, developed arthritis of the interphalangeal joint of the first finger of his left hand. Although the subacute clinical course and the magnetic resonance imaging findings required the differential diagnosis with an infectious process, the rest of the laboratory tests. other imaging studies and the course, together with a history of a similar episode a few years earlier on a finger of the other hand after a bee sting, enabled us to diagnosis this condition.

4.
Rheumatol Int ; 37(12): 2043-2047, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28905097

RESUMO

Sacroiliac joint (SIJ) involvement is a distinctive feature of spondyloarthritis (SpA). The main objective of this study was to assess the validity of color Doppler ultrasound (CDUS) in SIJ. This was a cross-sectional, blinded, case-control study of 108 cases divided into three groups: (a) 53 SpA patients with inflammatory back pain (IBP); (b) 28 SpA patients with no IBP; and (c) 27 healthy mechanical lumbar pain subjects. Physical examinations of the SIJs were assessed as positive or negative in each SIJ and were used as the gold standard. SIJs were examined with CDUS and spectral Doppler, and the SIJs were assessed as positive when both color Doppler and the resistance index (RI) were less than the cut-off point within the SIJs area. A total of 108 cases (53 female; mean age 36 ± 10 years old) were studied. The physical examination of the SIJs was positive in 38 patients (59 SIJs). Ultrasound detected Doppler signal within the SIJs in 37 cases (58 SIJs): 33 of them had symptomatic SpA (52 SIJs), 3 of them had asymptomatic SpA (5 SIJs), and 1 was a healthy control (1 SIJ). The accuracy of CDUS, when compared to physical SIJ examination, at the patient level in the overall group had a sensitivity of 70.3%, a specificity of 85.7%, a positive likelihood ratio of 4.9, and a negative likelihood ratio of 0.36. For the spectral Doppler RI, with an optimal cut-off point ≤0.75, the sensitivity was 76.2%, and the specificity was 77.8%. CDUS of SIJs seems to be a feasible and valid method for detecting active inflammation in patients with SpA.


Assuntos
Exame Físico/normas , Articulação Sacroilíaca/diagnóstico por imagem , Sacroileíte/diagnóstico por imagem , Espondilartrite/diagnóstico por imagem , Ultrassonografia Doppler em Cores , Adulto , Estudos de Casos e Controles , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Articulação Sacroilíaca/fisiopatologia , Sacroileíte/diagnóstico , Sensibilidade e Especificidade , Método Simples-Cego , Espondilartrite/diagnóstico , Ultrassonografia Doppler em Cores/economia
5.
Mol Diagn Ther ; 17(1): 49-56, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23329363

RESUMO

BACKGROUND: Calprotectin is potentially a more sensitive biomarker of disease activity in rheumatoid arthritis (RA) than conventional acute-phase proteins such as the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) because it directly reflects inflammation in the synovium and synovial fluid rather than systemic inflammatory activity. OBJECTIVE: The aim of this study was to evaluate relationships between serum calprotectin levels, disease activity, and response to treatment. Calprotectin was also investigated as a predictive marker of clinical response. METHODS: This observational study included selected cohorts of patients with RA treated at La Paz University Hospital, Madrid, Spain. Associations between serum calprotectin levels and clinical and laboratory parameters were analyzed in a cross-sectional cohort of 60 patients with varying disease activity, and changes in calprotectin levels in response to treatment with infliximab were analyzed at baseline and after 3 and 6 months of treatment in a longitudinal cohort of 20 patients with very active disease. RESULTS: In the cross-sectional cohort, calprotectin levels correlated with rheumatoid factor levels (r = 0.25; p < 0.05) but not with titers of antibodies to cyclic citrullinated peptide. Significant correlations were also observed between calprotectin levels and the 28 swollen joint count (28-SJC), Disease Activity Score based on a 28-joint count (DAS28), Simplified Disease Activity Index (SDAI), ESR, and CRP levels. In the longitudinal cohort, calprotectin levels at baseline were not predictive of response to treatment but significantly decreased during treatment in responders (p < 0.0001). CONCLUSION: Calprotectin levels strongly correlate with clinical and laboratory assessments of joint inflammation and also decrease in response to treatment, indicating that calprotectin is a promising marker for assessment and monitoring of disease activity in patients with RA. Investigations are required to further evaluate its diagnostic, prognostic, and therapeutic potential.


Assuntos
Artrite Reumatoide/sangue , Artrite Reumatoide/diagnóstico , Complexo Antígeno L1 Leucocitário/sangue , Proteínas da Fase Aguda/metabolismo , Adulto , Idoso , Anticorpos Monoclonais/uso terapêutico , Biomarcadores/sangue , Sedimentação Sanguínea , Proteína C-Reativa/metabolismo , Estudos Transversais , Determinação de Ponto Final , Feminino , Humanos , Infliximab , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Peptídeos Cíclicos/metabolismo , Prognóstico , Espanha , Líquido Sinovial/metabolismo , Membrana Sinovial/metabolismo
6.
Best Pract Res Clin Rheumatol ; 25(3): 407-21, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22100289

RESUMO

This article presents a review of the current approach to diagnostic and therapeutic conditions of septic arthritis. Acute septic arthritis is an uncommon, but potentially fatal, emergency. Early diagnosis as well as prompt and effective treatment are essential to avoid either irreversible joint destruction or even death. The clinical features of this condition are different in neonates, children and adults. The definitive diagnosis of septic arthritis requires the direct demonstration of bacteria in synovial fluid or on positive culture of the pathogen. A combination of antibiotics and the prompt removal of purulent material from the affected joint constitutes the mainstay of successful treatment. In addition, this article discusses, in particular, prosthetic joint infection and gonococcal arthritis.


Assuntos
Artrite Infecciosa , Artrite Infecciosa/diagnóstico , Artrite Infecciosa/epidemiologia , Artrite Infecciosa/microbiologia , Artrite Infecciosa/terapia , Gonorreia/complicações , Gonorreia/diagnóstico , Gonorreia/tratamento farmacológico , Gonorreia/microbiologia , Humanos , Prognóstico , Infecções Relacionadas à Prótese/diagnóstico , Infecções Relacionadas à Prótese/tratamento farmacológico , Fatores de Risco
7.
Reumatol. clín. (Barc.) ; 7(5): 314-322, sept.-oct. 2011. tab, ilus
Artigo em Espanhol | IBECS | ID: ibc-90949

RESUMO

Introducción: El objetivo de la revision sistematica fue evaluar la eficacia y la seguridad del tratamiento con RTX en pacientes con AR para la elaboracion del Documento de consenso de uso de rituximab en artritis reumatoide, un documento con recomendaciones basadas en la evidencia5 sobre el empleo del farmaco en situaciones clinicas dificiles en practica clinica habitual. Metodología: Se realizaron busquedas de los trabajos publicados desde enero de 2003 hasta septiembre de 2009 en Medline, EMBASE y la Cochrane Library y revision manual de los resumenes de los congresos de EULAR y ACR de 2003 a 2009 y de datos proporcionados por Roche Pharma. En la estrategia de busqueda se emplearon los siguientes terminos: «Rituximab», «Rheumatoid arthritis», «Anti-CD20», «Biologics». Dos autores (BHC yMGH)efectuaron la busqueda bibliografica por titulo y resumen. Despues dos autores (BHC y RAA) calificaron los trabajos segun la escala GRADE y los seleccionaron tras su revision en extenso. La extraccion de los datos para el analisis se realizo en formato en papel. Las medidas de desenlace evaluadas fueron para eficacia las propuestas por OMERACT13 (Outcome Measurements in Rheumatoid Arthritis Clinical Trials) y el grupo Cochrane de Estudio de Enfermedades Musculoesqueleticas, relevantes en practica clinica. Para seguridad se evaluaron: mortalidad, presencia de infecciones graves, efectos adversos graves, retiradas del estudio por cualquier causa, retiradas del estudio por efectos adversos graves, retiradas del estudio por reacciones a la infusion y reacciones graves relacionadas con la infusion. El analisis estadistico se realizo con el calculo del riesgo relativo y la odds ratio para variables dicotomicas (OR) y de la diferencia media entre el valor basal frente al final para variables continuas, se estimo la diferencia absoluta de riesgo con el programa RevMan 519 y el numero de pacientes necesario que tratar con las formulas y la calculadora de Cates20. Resultados: El RTX es un medicamento eficaz en el tratamiento de tres grupos de pacientes con artritis reumatoide: en fallo a MTX, fallo a anti-TNF y en pacientes sin exposicion previa a MTX. Es necesario tratar a 7 (5-10) pacientes con RTX frente a placebo para obtener una respuesta ACR70; 9 (6-15) para conseguir un DAS28 < 2,6 y 5 (4-8) para una mejoria en el HAQ> 0,2. La seguridad del farmaco fue similar a la del placebo, excepto para reacciones a la primera infusion en donde se necesita tratar 12 (8-26) pacientes con RTX frente a placebo para observar alguna reaccion a la primera infusion con premedicacion con corticoides. Las reacciones graves a la infusion tuvieron una incidencia de 0,7% en los pacientes del grupo tratado con RTX. No fue posible identificar un mayor incremento en el numero de infecciones graves posiblemente debido a problemas metodologicos, no obstante el riesgo de desarrollar infecciones graves en pacientes tratados con RTX parece ser comparable al de otros anti-TNF y biologicos (AU)


Introduction: The aim of the systematic review was to evaluate the safety and efficacy of rituximab for the treatment of rheumatoid arthritis patients, as part of the Consensus on the use of rituximab in rheumatoid arthritis. A document with evidence based recommendations5. Methods: All papers published from January 2003 to September 2009 were reviewed in a systematic way in Medline, EMBASE and Cochrane Library database. The Mesh terms used were: «Rituximab», «Rheumatoid arthritis», «and Anti-CD20», «Biologics». The abstracts of the EULAR and ACR congress of 2003 to 2009 were also reviewed, as well data of Roche Pharma. Two rheumatologists (BHC y MGH) made the bibliographic review by title and summary of each work. Two authors (BHC y RAA) selected them by quality according the GRADE SCALE after they review. The data were collected in paper. The outcomes evaluated were of efficacy in agreement with OMERACT13 (Outcome Measurements in Rheumatoid Arthritis Clinical Trials) and The Musculoskeletal Cochrane Study Group. The outcomes of safety evaluated were: mortality, severe infections, severe adverse events, withdraw for any cause, for severe adverse events, and for infusion related reactions. The review was conducted with Cochrane methodology. The odds ratio and relative risk for dichotomist variables; and mean difference between baseline and final measurements for continuous variables, and risk differences were calculated with RevMan 519. The number of patients needed to treat was calculated with Cates’ calculator20. Results: RTX is an effective drug in three groups of patients with RA: patients who fail to MTX, those who fail anti-TNF and in patients with no prior exposure to MTX. It is necessary to treat 7 (5-10) patients with RTX vs. placebo to obtain an ACR70 response; 9 (6-15) to achieve a DAS28 < 2.6; and 5 (4-8) to achieve a HAQ improvement >0.2. Safety of the drug was similar to that of placebo except for infusion reactions where 12 (8-26) patients need to be treated with RTX vs. placebo to see a reaction to the first infusion with steroid premedication. Severe adverse events to the infusion had an incidence of 0.7% in patients of the RTX treated group. It was impossible to identify a larger increase in the number of severe infections, probably due to methodological problems, however, the risk of developing infections in patients treated with RTX seems to be comparable to that of other anti-TNF and biologics (AU)


Assuntos
Humanos , Feminino , Pessoa de Meia-Idade , Artrite Reumatoide/tratamento farmacológico , Resultado do Tratamento , Avaliação de Eficácia-Efetividade de Intervenções , Antígenos CD20 , Viés , Razão de Chances
8.
Reumatol Clin ; 7(5): 314-22, 2011 Sep-Oct.
Artigo em Espanhol | MEDLINE | ID: mdl-21925447

RESUMO

INTRODUCTION: The aim of the systematic review was to evaluate the safety and efficacy of rituximab for the treatment of rheumatoid arthritis patients, as part of the Consensus on the use of rituximab in rheumatoid arthritis. A document with evidence based recommendations. METHODS: All papers published from January 2003 to September 2009 were reviewed in a systematic way in Medline, EMBASE and Cochrane Library database. The Mesh terms used were: "Rituximab", "Rheumatoid arthritis", "and Anti-CD20", "Biologics". The abstracts of the EULAR and ACR congress of 2003 to 2009 were also reviewed, as well data of Roche Pharma. Two rheumatologists (BHC y MGH) made the bibliographic review by title and summary of each work. Two authors (BHC y RAA) selected them by quality according the GRADE SCALE after they review. The data were collected in paper. The outcomes evaluated were of efficacy in agreement with OMERACT (Outcome Measurements in Rheumatoid Arthritis Clinical Trials) and The Musculoskeletal Cochrane Study Group. The outcomes of safety evaluated were: mortality, severe infections, severe adverse events, withdraw for any cause, for severe adverse events, and for infusion related reactions. The review was conducted with Cochrane methodology. The odds ratio and relative risk for dichotomist variables; and mean difference between baseline and final measurements for continuous variables, and risk differences were calculated with RevMan 5. The number of patients needed to treat was calculated with Cates' calculator. RESULTS: RTX is an effective drug in three groups of patients with RA: patients who fail to MTX, those who fail anti-TNF and in patients with no prior exposure to MTX. It is necessary to treat 7 (5-10) patients with RTX vs. placebo to obtain an ACR70 response; 9 (6-15) to achieve a DAS28 < 2.6; and 5 (4-8) to achieve a HAQ improvement > 0.2. Safety of the drug was similar to that of placebo except for infusion reactions where 12 (8-26) patients need to be treated with RTX vs. placebo to see a reaction to the first infusion with steroid premedication. Severe adverse events to the infusion had an incidence of 0.7% in patients of the RTX treated group. It was impossible to identify a larger increase in the number of severe infections, probably due to methodological problems, however, the risk of developing infections in patients treated with RTX seems to be comparable to that of other anti-TNF and biologics.


Assuntos
Anticorpos Monoclonais Murinos/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Anticorpos Monoclonais Murinos/efeitos adversos , Antirreumáticos/efeitos adversos , Humanos , Rituximab
9.
Reumatol Clin ; 7(1): 30-44, 2011 Jan-Feb.
Artigo em Espanhol | MEDLINE | ID: mdl-21794777

RESUMO

INTRODUCTION: Rituximab has been employed successfully for the treatment of Rheumatoid Arthritis (RA). However, its particular mechanism of action, as well as a lack of concrete guidelines for its management have generated doubts on its use. OBJECTIVE: To establish recommendations that facilitates the use of rituximab in common clinical practice. METHODS: In a first Delphi round, 9 expert rheumatologists got together to develop questions on those subjects generating most doubts on the efficacy and safety of the drug. These were adapted to perform a systematic review of the evidence, which was presented in a second meeting. Nominal groups were formed to respond to each question and give a recommendation. These recommendations were presented in a second Delphi round to a larger group of experts in rheumatology. Once again recommendations were discussed, modified and voted upon. Once approved, a vote on the degree of agreement for each recommendation was carried out. RESULTS: 17 recommendations were established, 10 regarding efficacy and 7 safety. All of the efficacy recommendations except 3 presented a good or moderate degree of evidence. Among the safety recommendations, 3 had a good or moderate degree of evidence while in the rest it was indirect, scarce or non-existent and a product of expert recommendation. The degree of agreement between experts was elevated for most of the recommendations. CONCLUSIONS: These recommendations attempt to clear doubts on the use of rituximab and establish guidelines for its use in daily practice. Efficacy recommendations have a high degree of evidence, allowing the clinician to be guided in therapeutic decisions. Safety recommendations have a lower degree of evidence.


Assuntos
Anticorpos Monoclonais Murinos/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Anticorpos Monoclonais Murinos/administração & dosagem , Anticorpos Monoclonais Murinos/efeitos adversos , Antígenos CD20/imunologia , Antirreumáticos/administração & dosagem , Antirreumáticos/efeitos adversos , Artrite Reumatoide/imunologia , Linfócitos B/efeitos dos fármacos , Linfócitos B/imunologia , Ensaios Clínicos como Assunto , Técnica Delfos , Relação Dose-Resposta a Droga , Relação Dose-Resposta Imunológica , Medicina Baseada em Evidências , Insuficiência Cardíaca/etiologia , Hepatite B Crônica/complicações , Humanos , Hospedeiro Imunocomprometido , Imunoglobulina G/biossíntese , Imunoglobulina M/biossíntese , Falência Hepática/etiologia , Doenças Pulmonares Intersticiais/etiologia , Segunda Neoplasia Primária/etiologia , Rituximab , Vacinação
10.
Reumatol. clín. (Barc.) ; 7(1): 30-44, ene.-feb. 2011. tab
Artigo em Espanhol | IBECS | ID: ibc-84610

RESUMO

Introducción. El rituximab se ha empleado con éxito en el tratamiento de la artritis reumatoide (AR). Sin embargo, su particular mecanismo de acción, así como la ausencia de pautas concretas en su manejo, hace que se hayan generado dudas sobre su utilización. Objetivo. Establecer recomendaciones que faciliten el empleo de rituximab en la práctica clínica habitual. Métodos. En una primera ronda Delphi, se reunieron nueve reumatólogos expertos que desarrollaron preguntas sobre los temas con mayor duda sobre eficacia y seguridad del fármaco. Estas se adecuaron para hacer una revisión sistemática de la evidencia, que se presentó en una segunda reunión. Se formaron grupos nominales para dar respuesta a cada pregunta y emitir la recomendación. Estas recomendaciones fueron presentadas en una segunda ronda Delphi a un grupo ampliado de reumatólogos expertos. De nuevo se discutieron, se modificaron y se votaron las recomendaciones. Una vez aprobada cada recomendación, se votó el grado de acuerdo. Resultados. Se establecieron 17 recomendaciones: diez de eficacia y siete de seguridad. Todas las recomendaciones de eficacia, excepto tres, presentaron un nivel de evidencia bueno o moderado. Entre las recomendaciones de seguridad, tres presentaron un nivel de evidencia bueno o moderado, mientras que para el resto la evidencia fue indirecta, escasa o nula y son producto de las recomendaciones de los expertos. El grado de acuerdo entre expertos fue elevado para la mayoría de las recomendaciones. Conclusiones. Estas recomendaciones pretenden aclarar dudas sobre el uso de rituximab y establecer pautas de empleo en la práctica clínica. Las recomendaciones de eficacia tienen un nivel de evidencia alto y permiten guiar al médico en decisiones terapéuticas. Las recomendaciones de seguridad tienen un nivel de evidencia menor (AU)


Introduction. Rituximab has been employed successfully for the treatment of Rheumatoid Arthritis (RA). However, its particular mechanism of action, as well as a lack of concrete guidelines for its management have generated doubts on its use. Objective. To establish recommendations that facilitates the use of rituximab in common clinical practice. Methods. In a first Delphi round, 9 expert rheumatologists got together to develop questions on those subjects generating most doubts on the efficacy and safety of the drug. These were adapted to perform a systematic review of the evidence, which was presented in a second meeting. Nominal groups were formed to respond to each question and give a recommendation. These recommendations were presented in a second Delphi round to a larger group of experts in rheumatology. Once again recommendations were discussed, modified and voted upon. Once approved, a vote on the degree of agreement for each recommendation was carried out. Results. 17 recommendations were established, 10 regarding efficacy and 7 safety. All of the efficacy recommendations except 3 presented a good or moderate degree of evidence. Among the safety recommendations, 3 had a good or moderate degree of evidence while in the rest it was indirect, scarce or non-existent and a product of expert recommendation. The degree of agreement between experts was elevated for most of the recommendations. Conclusions. These recommendations attempt to clear doubts on the use of rituximab and establish guidelines for its use in daily practice. Efficacy recommendations have a high degree of evidence, allowing the clinician to be guided in therapeutic decisions. Safety recommendations have a lower degree of evidence (AU)


Assuntos
Humanos , Masculino , Feminino , Artrite Reumatoide/tratamento farmacológico , Medicina Baseada em Evidências/métodos , Terapia Biológica , Antirreumáticos/uso terapêutico , Metotrexato/uso terapêutico , Medicina Baseada em Evidências/estatística & dados numéricos , Medicina Baseada em Evidências/tendências , Terapia Biológica/métodos , Terapia Biológica/tendências , Avaliação de Eficácia-Efetividade de Intervenções , Enquete Socioeconômica
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