Assessment of osteoarthritis candidate genes in a meta-analysis of nine genome-wide association studies.

OBJECTIVE: To assess candidate genes for association with osteoarthritis (OA) and identify promising genetic factors and, secondarily, to assess the candidate gene approach in OA. METHODS: A total of 199 candidate genes for association with OA were identified using Human Genome Epidemiology (HuGE) Navigator. All of their single-nucleotide polymorphisms (SNPs) with an allele frequency of >5% were assessed by fixed-effects meta-analysis of 9 genome-wide association studies (GWAS) that included 5,636 patients with knee OA and 16,972 control subjects and 4,349 patients with hip OA and 17,836 control subjects of European ancestry. An additional 5,921 individuals were genotyped for significantly associated SNPs in the meta-analysis. After correction for the number of independent tests, P values less than 1.58 × 10(-5) were considered significant. RESULTS: SNPs at only 2 of the 199 candidate genes (COL11A1 and VEGF) were associated with OA in the meta-analysis. Two SNPs in COL11A1 showed association with hip OA in the combined analysis: rs4907986 (P = 1.29 × 10(-5) , odds ratio [OR] 1.12, 95% confidence interval [95% CI] 1.06-1.17) and rs1241164 (P = 1.47 × 10(-5) , OR 0.82, 95% CI 0.74-0.89). The sex-stratified analysis also showed association of COL11A1 SNP rs4908291 in women (P = 1.29 × 10(-5) , OR 0.87, 95% CI 0.82-0.92); this SNP showed linkage disequilibrium with rs4907986. A single SNP of VEGF, rs833058, showed association with hip OA in men (P = 1.35 × 10(-5) , OR 0.85, 95% CI 0.79-0.91). After additional samples were genotyped, association at one of the COL11A1 signals was reinforced, whereas association at VEGF was slightly weakened. CONCLUSION: Two candidate genes, COL11A1 and VEGF, were significantly associated with OA in this focused meta-analysis. The remaining candidate genes were not associated.

Actualización del Documento de Consenso de la Sociedad Española de Reumatología sobre el uso de terapias biológicas en la artritis reumatoide / Update of the Consensus Statement of the Spanish Society of Rheumatology on the management of biologic therapies in rheumatoid arthritis

Objetivo Servir de referencia para reumatólogos e implicados en el tratamiento de la artritis reumatoide que vayan a utilizar o consideren la utilización de terapias biológicas en su manejo. Métodos Las recomendaciones se emitieron siguiendo la metodología de grupos nominales y basadas en revisiones sistemáticas. El nivel de evidencia y el grado de recomendación se clasificaron según el modelo del Center for Evidence Based Medicine de Oxford y el grado de acuerdo se extrajo por técnica Delphi. Resultados Se realizan recomendaciones sobre el uso de los siete agentes biológicos disponibles para la artritis reumatoide en la actualidad en nuestro país. El objetivo del tratamiento es lograr la remisión de la enfermedad lo más precozmente posible. Se revisan las indicaciones y matizaciones del uso de terapias biológicas y cuál debe ser la evaluación previa y la vigilancia del paciente con estos fármacos. Conclusiones Se presentan las actualizaciones a las recomendaciones SER para el uso de terapias biológicas en pacientes con artritis reumatoide(AU)

Objective To provide a reference to rheumatologists and to those involved in the treatment of RA who are using, or about to use biologic therapy. Methods Recommendations were developed following a nominal group methodology and based on systematic reviews. The level of evidence and grade of recommendation were classified according to the model proposed by the Center for Evidence Based Medicine at Oxford. The level of agreement was established through Delphi technique. Results We have produced recommendations on the use of the seven biologic agents available for RA in our country. The objective of treatment is to achieve the remission of the disease as quickly as possible. Indications and nuances regarding the use of biologic therapy were reviewed as well as the evaluation that should be performed prior to administration and the follow up of patients undergoing this therapy. Conclusions We present an update on the SER recommendations for the use of biologic therapy in patients with RA(AU)

[Update of the Consensus Statement of the Spanish Society of Rheumatology on the management of biologic therapies in rheumatoid arthritis]. / Actualización del Documento de Consenso de la Sociedad Española de Reumatología sobre el uso de terapias biológicas en la artritis reumatoide.

OBJECTIVE: To provide a reference to rheumatologists and to those involved in the treatment of RA who are using, or about to use biologic therapy. METHODS: Recommendations were developed following a nominal group methodology and based on systematic reviews. The level of evidence and grade of recommendation were classified according to the model proposed by the Center for Evidence Based Medicine at Oxford. The level of agreement was established through Delphi technique. RESULTS: We have produced recommendations on the use of the seven biologic agents available for RA in our country. The objective of treatment is to achieve the remission of the disease as quickly as possible. Indications and nuances regarding the use of biologic therapy were reviewed as well as the evaluation that should be performed prior to administration and the follow up of patients undergoing this therapy. CONCLUSIONS: We present an update on the SER recommendations for the use of biologic therapy in patients with RA.

[Efficacy and security of tumor necrosis factor antagonists in the treatment of rheumatoid arthritis]. / Eficacia y seguridad de los tratamientos antagonistas del factor de necrosis tumoral en la artritis reumatoide.

In the last decade, tumor necrosis factor (TNF) antagonists had supposed an important therapeutic advance in the treatment of patients with rheumatoid arthritis (RA) in both early and established RA. Three agents currently available--infliximab, etanercept, and adalimumab--have been designed to modify the biologic effects of TNF. Infliximab and adalimumab are monoclonal antibodies, whereas etanercept is a soluble protein, with different pharmacokinetic and pharmacodynamic properties, conditioning some possible adverse effects. Although comparative studies are not available, the 3 drugs have demonstrated efficacy and security, with a better quality of life of patients with RA. Infliximab, etanercept and adalimumab have been proved alone and in combination with methotrexate, with a better therapeutic, clinical, radiological and functional response in the group under combined therapy. Both clinical trials and post-market experience have demonstrated the security of these drugs, minimizing the risks with an adequate selection of patients.

Eficacia y seguridad de los tratamientos antagonistas del factor de necrosis tumoral en la artritis reumatoide / Efficacy and security of tumor necrosis factor antagonists in the treatment of rheumatoid arthritis

Los fármacos antagonistas del factor de necrosis tumoral (TNF) han supuesto una importante arma terapéutica en el tratamiento de los pacientes con artritis reumatoide (AR) en la última década, tanto en la AR establecida como en la artritis de inicio. Los 3 agentes comercializados actualmente ­infliximab, etanercept y adalimumab­ han sido concebidos para modificar los efectos biológicos del TNF. El infliximab y el adalimumab son anticuerpos monoclonales, mientras que el etanercept es una proteína soluble, por lo que sus propiedades tanto farmacocinéticas como farmacodinámicas son diferentes, lo que condiciona algunos de los efectos adversos posibles. Aunque no disponemos en la actualidad de estudios comparativos entre ellos, los 3 agentes han demostrados ser fármacos eficaces y seguros, con lo que mejoran la calidad de vida de los pacientes con AR. Tanto el infliximab como el etanercept y el adalimumab se han ensayado con y sin metotrexato, con mejor respuesta clínica, radiológica y funcional en los casos de tratamiento combinado. Tanto en los ensayos clínicos como en los estudios poscomercialización se ha demostrado la seguridad de estos fármacos y que los riesgos se minimizan con una selección adecuada de los pacientes

In the last decade, tumor necrosis factor (TNF) antagonists had supposed an important therapeutic advance in the treatment of patients with rheumatoid arthritis (RA) in both early and established RA. Three agents currently available ­infliximab, etanercept, and adalimumab­ have been designed to modify the biologic effects of TNF. Infliximab and adalimumab are monoclonal antibodies, whereas etanercept is a soluble protein, with different pharmacokinetic and pharmacodynamic properties, conditioning some possible adverse effects. Although comparative studies are not available, the 3 drugs have demonstrated efficacy and security, with a better quality of life of patients with RA. Infliximab, etanercept and adalimumab have been proved alone and in combination with methotrexate, with a better therapeutic, clinical, radiological and functional response in the group under combined therapy. Both clinical trials and post-market experience have demonstrated the security of these drugs, minimizing the risks with an adequate selection of patients

Primeras notificaciones espontáneas de sospechas de reacciones adversas a los nuevos antiinflamatorios selectivos sobre la ciclooxigenasa-2 / First spontaneous reports of adverse drug reactions to the new selective COX-2 non-steroideal anti-inflammatory drugs

No disponible

Fisiopatología de la ciclooxigenasa-1 y ciclooxigenasa-2 / The physiopathology of cyclooxygenase-1 and cyclooxygenase-2

No disponible

La genética de la artritis reumatoide / Genetics of rheumatoid arthritis

No disponible