[Certolizumab pegol]. / Certolizumab pegol.

Certolizumab pegol is a new anti-TNF drug formed by the Fab' fragment of a humanized mouse monoclonal antibody bound to two molecules of polyethylene glycol. Certolizumab pegol recognizes and binds to human TNF-α, both in its soluble and membrane bound form, and has shown clinical efficacy in controlled trials for the treatment of RA and Crohns' disease. In this review we summarize the structural characteristics and clinical efficacy data, as well as safety data of this anti-TNF agent in patients with RA.

Certolizumab pegol / Certolizumab pegol

El certolizumab pegol es un nuevo fármaco anti-TNF formado por el fragmento Fab’ de un anticuerpo monoclonal murino humanizado unido a dos moléculas de polietilenglicol. El certolizumab pegol reconoce y neutraliza el TNF-α humano, soluble y unido a membrana, y ha demostrado eficacia clínica en ensayos controlados en la AR y en la enfermedad de Crohn. En esta revisión se resumen las características estructurales y los datos de eficacia clínica, de prevención del daño estructural, así como los datos de seguridad de este anti-TNF en pacientes con AR (AU)

Certolizumab pegol is a new anti-TNF drug formed by the Fab’ fragment of a humanized mouse monoclonal antibody bound to two molecules of polyethylene glycol. Certolizumab pegol recognizes and binds to human TNF-α, both in its soluble and membrane bound form, and has shown clinical efficacy in controlled trials for the treatment of RA and Crohns’ disease. In this review we summarize the structural characteristics and clinical efficacy data, as well as safety data of this anti-TNF agent in patients with RA (AU)

Otras dianas terapéuticas distintas a las citocinas / Non-cytokine therapeutic targets

La llegada de los fármacos anti-TNF-α (tumor necrosis factor alpha‘ factor de necrosis tumoral alfa’) a la clínica ha sido el resultado más exitoso de la investigación traslacional. Sin embargo, la experiencia ha demostrado que estos compuestos no consiguen inducir la remisión clínica en la mitad de los pacientes con artritis reumatoide (AR). Recientemente se han puesto a disposición en el mercado fármacos biológicos no dirigidos contra citocinas que deplecionan las células B o interfieren con la activación de las células T y que también han mostrado eficacia en el control de la actividad de la AR. Una segunda generación de compuestos contra la célula B está en desarrollo de parte de diversas empresas farmacéuticas. Es de esperar que estos productos mejoren la inmunogenicidad y la posología del rituximab, pero es poco probable que incrementen las tasas de remisión alcanzadas por los anti-TNF-α. Actualmente, la regulación de la transducción de señales se ha convertido en un campo muy importante en el desarrollo de los fármacos, y pequeñas moléculas inhibidoras de vías de señalización intracelular se están ensayando como nuevos antiinflamatorios. Para las enfermedades reumáticas, los inhibidores específicos de JAK3 y Syk son, hasta ahora, los compuestos que han mostrado mejores resultados y representan un avance significativo respecto a los inhibidores de la p38 MAPK (mitogen-activated protein kinase ' proteína cinasa activada por mitógeno') (AU)

The arrival of anti-TNF-α to the clinic has been the most successful example of translational research. However, clinical experience has shown that these compounds do not induce clinical remission in half of rheumatoid arthritis (RA) patients. Recently, new biological drugs against non-cytokine targets have been available for RA patients. These compounds deplete B cells or interfere with the activation of T cells and have also shown effectiveness in controlling signs, symptoms and structural damage progression in RA. Second generation B-cell depletion therapies are progressing in the pipeline of several pharmaceutical companies. These compounds will likely improve the immunogenicity and formulation of rituximab, but it is improbable that they will improve the remission rate achieved by the anti-TNF-αδρυγσ. Currently, regulation of signal transduction has evolved into an important field of drug research, and small molecule inhibitors for a number of pathways are tested as new anti-inflammatory agents. For rheumatic diseases, specific Jak3 and Syk inhibitors are, so far, the most successful compounds representing a significant advance over p38 mitogen-activated protein kinase (MAPK) inhibitors (AU)

Uso apropiado de los antiinflamatorios no esteroideos en reumatología: documento de consenso de la Sociedad Española de Reumatología y el Colegio Mexicano de Reumatología / Appropriate use of non-steroidal anti-inflammatory drugs in rheumatology: guidelines from the Spanish Society of Rheumatology and the Mexican College of Rheumatology

Objetivos: Elaborar recomendaciones para el uso apropiado de AINE en reumatología. Métodos: Se utilizó una metodología modificada de RAND/UCLA. Se seleccionaron dos grupos de panelistas, uno por el CMR y otro por la SER. A partir de grupos nominales, se obtuvieron propuestas de recomendaciones, que fueron sometidas a la prueba de acuerdo entre los reumatólogos de ambas sociedades mediante encuesta Delphi a dos rondas. Del análisis de la segunda ronda Delphi, se extrajeron las recomendaciones finales y posteriormente se revisó el nivel de evidencia y el grado de acuerdo de la recomendación según el Centro de Medicina Basada en la Evidencia de Oxford. Finalmente, se efectuó revisión sistemática de cinco recomendaciones sin acuerdo. Resultados: Se presentan recomendaciones sobre el uso seguro de los AINE en las enfermedades reumáticas, con base en la mejor evidencia disponible, la opinión de expertos, el acuerdo entre reumatólogos y la revisión de la literatura. La tendencia es disminuir la frecuencia, la duración y la dosis de AINE en favor de medidas no farmacológicas, analgésicos o fármacos modificadores de los síntomas o del curso de la enfermedad. Además, es obligado identificar perfiles de mayor riesgo de toxicidad, en especial gastrointestinal y cardiovascular. Se recomiendan pautas de actuación y monitorización en los diferentes grupos de riesgo y en pacientes con empleo de antiagregantes plaquetarios, anticoagulación o con terapias concomitantes. El porcentaje de acuerdo es elevado en la mayoría de los casos. Conclusiones: Los AINE son medicamentos seguros y eficaces en el tratamiento de las afecciones reumáticas. No obstante, dado su perfil de riesgo, es necesario individualizar su uso (AU)

Objective: To develop guidelines for the appropriate use of NSAIDs in rheumatology. Methods: We used a methodology modified from the one developed by RAND/UCLA. Two groups of panellists were selected, one by the CMR and another by the SER. Recommendations were proposed from nominal groups and the agreement to them was tested among rheumatologists from both societies by a tworound Delphi survey. The analysis of the second Delphi round supported the generation of the final set of recommendations and the assignment of a level of agreement to each of them. Systematic reviews of five recommendations in which the agreement was low or was divided were also carried out. Results: Here we present recommendations for the safe use of NSAIDs in rheumatic diseases, based on the best available evidence, expert opinion, the agreement among rheumatologists, and literature review. The trend is to reduce the frequency, duration and dose of NSAIDs in favour of non-pharmacological measures, analgesic drugs or disease modifying drugs. In addition, the recommendations help to identify profiles for increased toxicity, with an emphasis on gastrointestinal and cardiovascular risks. The recommendations deal with the course of action and monitoring in different risk groups and in patients using antiplatelet or anticoagulant drugs. The overall level of agreement is high. Conclusions: The NSAIDs are safe and effective drugs for the treatment of rheumatic diseases. However, it is necessary to individualize its use according to their risk profile (AU)

[Appropriate use of non-steroidal anti-inflammatory drugs in rheumatology: guidelines from the Spanish Society of Rheumatology and the Mexican College of Rheumatology]. / Uso apropiado de los antiinflamatorios no esteroideos en reumatología: documento de consenso de la Sociedad Española de Reumatología y el Colegio Mexicano de Reumatología.

OBJECTIVE: To develop guidelines for the appropriate use of NSAIDs in rheumatology. METHODS: We used a methodology modified from the one developed by RAND/UCLA. Two groups of panellists were selected, one by the CMR and another by the SER. Recommendations were proposed from nominal groups and the agreement to them was tested among rheumatologists from both societies by a tworound Delphi survey. The analysis of the second Delphi round supported the generation of the final set of recommendations and the assignment of a level of agreement to each of them. Systematic reviews of five recommendations in which the agreement was low or was divided were also carried out. RESULTS: Here we present recommendations for the safe use of NSAIDs in rheumatic diseases, based on the best available evidence, expert opinion, the agreement among rheumatologists, and literature review. The trend is to reduce the frequency, duration and dose of NSAIDs in favour of non-pharmacological measures, analgesic drugs or disease modifying drugs. In addition, the recommendations help to identify profiles for increased toxicity, with an emphasis on gastrointestinal and cardiovascular risks. The recommendations deal with the course of action and monitoring in different risk groups and in patients using antiplatelet or anticoagulant drugs. The overall level of agreement is high. CONCLUSIONS: The NSAIDs are safe and effective drugs for the treatment of rheumatic diseases. However, it is necessary to individualize its use according to their risk profile.

[Non-cytokine therapeutic targets]. / Otras dianas terapéuticas distintas a las citocinas.

The arrival of anti-TNF-α to the clinic has been the most successful example of translational research. However, clinical experience has shown that these compounds do not induce clinical remission in half of rheumatoid arthritis (RA) patients. Recently, new biological drugs against non-cytokine targets have been available for RA patients. These compounds deplete B cells or interfere with the activation of T cells and have also shown effectiveness in controlling signs, symptoms and structural damage progression in RA. Second generation B-cell depletion therapies are progressing in the pipeline of several pharmaceutical companies. These compounds will likely improve the immunogenicity and formulation of rituximab, but it is improbable that they will improve the remission rate achieved by the anti-TNF-α δρυγσ. Currently, regulation of signal transduction has evolved into an important field of drug research, and small molecule inhibitors for a number of pathways are tested as new anti-inflammatory agents. For rheumatic diseases, specific Jak3 and Syk inhibitors are, so far, the most successful compounds representing a significant advance over p38 mitogen-activated protein kinase (MAPK) inhibitors.

La célula B en la patogenia de la artritis reumatoide / The B cell in the pathogenesis of rheumatoid arthritis

Hasta hace poco tiempo se consideraba que las células B tenían un papel secundario en la patogenia de la artritis reumatoide, limitado a la producción de autoanticuerpos. Sin embargo, la sorprendente buena respuesta clínica que la depleción sistémica de las células B ha demostrado en ensayos clínicos controlados y aleatorizados con pacientes con artritis reumatoide ha revitalizado el interés por el papel del linfocito B en la patogenia de esta enfermedad autoinmunitaria. Diversas evidencias indican que las células B pueden regular el curso de la respuesta inmunitaria mediante mecanismos alternativos no dependientes de la producción de anticuerpos. Estos mecanismos incluyen la presentación de antígenos y la liberación de factores solubles como citocinas proinflamatorias, metaloproteasas y quimiocinas. En esta revisión se resumen los datos experimentales que indican que la célula B participa en la patogenia de la artritis reumatoide mediante un mecanismo multifactorial (AU)

Classically, B-cells have been considered to play a secondary role in the pathogenesis of rheumatoid arthritis, restricted to the production of auto-antibodies. Nevertheless, the unexpected good clinical response that the systemic depletion of B-cells has demonstrated in a well-controlled clinical trial in patients with rheumatoid arthritis has revitalized the interest in this cell type in the pathogenesis of this autoimmune disease. Several evidences suggest that B-cells can regulate the course of the immune response through antibody production independent mechanisms. These mechanisms include antigen presentation and the release of soluble factors such as proinflammatory cytokines, metalloproteinases, and chemokines. This article reviews experimental data supporting that the participation of B-cells in the pathogenesis of rheumatoid arthritis occurs through multiple mechanisms (AU)

[The B cell in the pathogenesis of rheumatoid arthritis]. / La célula B en la patogenia de la artritis reumatoide.

Classically, B-cells have been considered to play a secondary role in the pathogenesis of rheumatoid artritis, restricted to the production of auto-antibodies. Nevertheless, the unexpected good clinical response that the systemic depletion of B-cells has demonstrated in a well-controlled clinical trial in patients with rheumatoid artritis has revitalized the interest in this cell type in the pathogenesis of this autoimmune disease. Several evidences suggest that B-cells can regulate the course of the immune response through antibody productionindependent mechanisms. These mechanisms include antigen presentation and the release of soluble factors such as proinflammatory cytokines, metalloproteinases, and chemokines. This article reviews experimental data supporting that the participation of B-cells in the pathogenesis of rheumatoid arthritis occurs through multiple mechanisms.

Evidencias científicas para la gastroprotección por AINE y esteroides / Scientific evidence for gastroprotection by NSAIDS and steroids

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