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Objective To assess the effectiveness, safety and cost of Etanercept biosimilar in patients with rheumatoid arthritis (RA), spondyloarthritis (SpA) and psoriatic arthritis (PsA) compared to the standard drug in real clinical practice. Patients and methods Retrospective observational study. Case series of 138 patients with RA, SpA or PsA treated with at least one dose of Benepali® (n = 79) or Enbrel® (n = 59). Drug retention time was the primary efficacy endpoint compared to the biosimilar and the original. The proportion of patients achieving low disease activity or remission after 52 weeks was used as the secondary outcome. Safety was assessed by means of the adverse effects incidence rate. A cost minimization analysis was performed. Results No differences were observed regarding treatment retention time between drugs (median [95% confidence interval, 95% CI] at 12.0 months [10.2-12.0] for the biosimilar and 12.0 months [12.0-12.0] for the original). Similar improvements, in terms of inflammatory activity and physical function, were obtained after 52 weeks except for patients with SpA and PsA who, in general, experienced improvements of BASDAI and ASDAS with the original compared with the biosimilar. No significant differences were observed in the total number of adverse effects (.43 events/patient-years versus the biosimilar and .53 versus the original). Using the biosimilar in place of the original drug resulted in a net savings of 118,383.55 € (1,747.20 €/patient-years) for the hospital. Conclusion The biosimilar Benepali is as effective and safe as the original and much more cost-effective.

Objective To assess the effectiveness, safety and cost of Etanercept biosimilar in patients with rheumatoid arthritis (RA), spondyloarthritis (SpA) and psoriatic arthritis (PsA) compared to the standard drug in real clinical practice. Patients and methods Retrospective observational study. Case series of 138 patients with RA, SpA or PsA treated with at least one dose of Benepali® (n = 79) or Enbrel® (n = 59). Drug retention time was the primary efficacy endpoint compared to the biosimilar and the original. The proportion of patients achieving low disease activity or remission after 52 weeks was used as the secondary outcome. Safety was assessed by means of the adverse effects incidence rate. A cost minimization analysis was performed. Results No differences were observed regarding treatment retention time between drugs (median [95% confidence interval, 95% CI] at 12.0 months [10.2–12.0] for the biosimilar and 12.0 months [12.0–12.0] for the original). Similar improvements, in terms of inflammatory activity and physical function, were obtained after 52 weeks except for patients with SpA and PsA who, in general, experienced improvements of BASDAI and ASDAS with the original compared with the biosimilar. No significant differences were observed in the total number of adverse effects (.43 events/patient-years versus the biosimilar and .53 versus the original). Using the biosimilar in place of the original drug resulted in a net savings of 118,383.55 € (1,747.20 €/patient-years) for the hospital. Conclusion The biosimilar Benepali is as effective and safe as the original and much more cost-effective.

Objectives To study the differences between rheumatoid arthritis (RA)-interstitial lung disease (ILD) patients and RA patients without ILD in severity markers and disease activity and to identify factors associated with the presence of ILD in RA patients. Patients and methods Patients: RA-ILD patients selected from a multicentre cohort in Andalusia, Spain. Controls: RA-patients without ILD paired by sex, age and disease duration. Protocol: RA patients are reviewed every 3–6 months in rheumatology consultation. All patients are reviewed according to a predetermined protocol with systematic data collection. Outcomes: description of ILD type, differences in severity markers and disease activity in both groups. Other variables: ILD type by imaging technique (HRCT): nonspecific interstitial pneumonia (NSIP)/usual interstitial pneumonia (UIP). Lung function by PTF. Activity and severity markers of arthritis by DAS28-ESR, HAQ, RF, ACPA and erosions. Treatment with DMARD. Statistical analysis: descriptive and paired T-test or Chi-square test followed by binary logistic regression (DV: ILD in patients with RA). Results Eighty-two patients were included, 41 RA-ILD and 41 RA controls. RF and ACPA positivity, serositis and osteoporosis were more frequent in RA-ILD patients. No significant differences in DAS28 were observed (P = .145) between RA-ILD and RA control patients. RA-ILD patients presented worse HAQ scores (P = .006). All patients were treated with disease modifying antirheumatic drugs (DMARDs). The risk of developing ILD in RA patients is tripled by a history of smoking or the presence of erosive arthritis (R2 = .36). Conclusions The results of our study support the higher frequency of UIP and NSIP in RA patients. DLCO is the most sensitive parameter to detect ILD in RA patients. Our study showed that ILD in RA patients was associated with RA severity (presence of erosions and ACPA) and with a history of smoking.

Resumen Objetivos Estudiar las diferencias en pacientes con artritis reumatoide (AR) y enfermedad pulmonar intersticial (EPID) y pacientes con AR sin EPID, e identificar factores asociados con la EPID en pacientes con AR. Pacientes y metodos Estudio observacional de casos y controles. Pacientes: se seleccionaron pacientes de una cohorte con AR y EPID de diferentes centros de Andalucia. Controles: pacientes con AR sin EPID pareados por edad, genero y tiempo de evolucion. Protocolo: los pacientes con AR se revisan cada 3-6 meses en consulta. Todos los pacientes son revisados de acuerdo con un protocolo predeterminado con recogida de datos sistematica. Desenlaces: descripcion del tipo radiologico de EPID, diferencias en los marcadores de gravedad en casos y controles y en la actividad de la enfermedad. Otras variables: descripcion del tipo de EPID por TACAR: neumonia intersticial usual (NIU), neumonia intersticial no especifica (NINE) y de la funcion pulmonar por PFR; marcadores de actividad y gravedad de artritis: DAS28, HAQ, FR, ACPA, erosiones. Tratamiento con FAME. Analisis: descriptivo, χ2 o t de Student, seguida de regresion logistica binaria (Vd:EPID en pacientes con AR). Resultados Se incluyeron 82 pacientes: 41 con AR y EPID y 41 controles AR sin EPID. Los pacientes con EPID presentaron un mayor porcentaje de pacientes con FR y ACPA positivos y una mayor frecuencia de serositis y osteoporosis. No hubo diferencias significativas en DAS28 en casos y controles(p = 0,145), pero los pacientes de AR con EPID presentaron peor HAQ (p = 0,006). Todos los pacientes estaban en tratamiento con FAME. El analisis multivariante mostro que los pacientes con AR exfumadores y con artritis erosiva triplicaron el riesgo de presentar EPID (R2 = 0,36). Conclusiones Los resultados de nuestro estudio apoyan la mayor frecuencia de NIU y NINE en pacientes con AR, asi como la alteracion de DLCO como el parametro mas importante. Los pacientes con AR y EPID se asociaron con una enfermedad mas grave (erosiones y ACPA) y con el tabaco.

Objectives To describe the therapeutic management of rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS) in patients initiating treatment with biological agents. Materials and methods Observational, retrospective, longitudinal study in 33 Spanish hospitals. Patients with RA, PsA and AS starting treatment with biological agents between September 2009 and August 2010 and a follow-up longer than 3 years were included. Clinical-demographic characteristics, drugs, biological therapy survival, and reasons for discontinuation or switching were analysed. Results Four hundred and sixty-three patients were included (183 RA, 119 PsA and 161 AS), with a mean follow-up of 3.8 years. At the end of follow-up, a high proportion continued with the first biological prescribed (41.0% of RA, 59.7% of PsA and 51.6% of AS), 31.1%, 47.9% and 42.9% of RA, PsA and AS patients requiring dosage adjustments, respectively. There was temporary discontinuation in 8.2%, 8.4% and 15.5% of patients, and a switch of biologic agent was required in 37.7%, 26.1% and 24.2%. Definitive discontinuation occurred in 13.1%, 5.9% and 8.7% of RA, PsA and AS patients, respectively. Mean time to discontinuation or switching was 30.1 months for RA and 35.7 months for PsA and AS. Conclusions Our results suggest that, in practice, half of patients with RA and two thirds with PsA or AS maintained the first biological, but with frequent dose adjustments.

Resumen Objetivo Generar recomendaciones sobre el bloqueo de la interleucina 6 (IL-6) en pacientes con artritis reumatoide (AR), basadas en la mejor evidencia y experiencia. Metodos Se selecciono a 10 expertos reumatologos en el manejo de los inhibidores de la IL-6. Los 2 coordinadores generaron 23 preguntas sobre el bloqueo de la IL-6 en la AR (perfiles de indicacion, eficacia, seguridad, etc.) para ser contestadas mediante una revision sistematica de la literatura. Con base en las preguntas se definieron los criterios de inclusion y exclusion, y las estrategias de busqueda (para interrogar Medline, Embase y la Cochrane Library). Dos revisores seleccionaron los articulos resultantes de la busqueda. Se generaron tablas de evidencia. Paralelamente, se evaluaron abstracts de congresos de EULAR y ACR. Con toda esta evidencia los coordinadores propusieron 8 recomendaciones preliminares que se evaluaron, discutieron y votaron en una reunion de grupo nominal con el resto de los expertos. Para cada recomendacion se establecio el nivel de evidencia y grado de recomendacion, y el grado de acuerdo mediante un Delphi. Se definio acuerdo si al menos el 80% de los participantes contestaban si a la recomendacion (si o no). Resultados Las 8 recomendaciones preliminares se aceptaron tras el Delphi. Abarcan aspectos como su uso en monoterapia, en combinacion, en pacientes refractarios o intolerantes, la evaluacion de su respuesta, la optimizacion o la gestion del riesgo. Conclusiones Este documento pretende resolver algunos interrogantes clinicos habituales y facilitar la toma de decisiones con el bloqueo de la IL-6 en el manejo de la AR.

To describe comorbid conditions in patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD) and to analyze factors associated with multimorbidity.Nested case-cohort study of 2 prospective cohorts: one with RA-ILD (cases) and another with RA but not ILD (controls). The cohorts were matched for age, sex, and time since diagnosis. Multimorbidity was defined as the co-occurrence of 2 or more chronic diseases, in addition to RA and ILD. We evaluated the comorbid conditions included in the Charlson Comorbidity Index, cardiovascular risk factors, neuropsychiatric conditions, and other frequent conditions in RA. We also recorded clinical-laboratory variables, inflammatory activity according to the 28-joint Disease Activity Score, C-reactive protein (CRP), physical function, and pulmonary function. We performed 2 multivariate analyses to identify factors associated with multimorbidity in RA and RA-ILD.The final study population comprised 110 cases and 104 controls. Multimorbidity was more frequent among cases than controls (80 [72.7] vs 60 [57.7]; p = 0.021). In both groups, multimorbidity was associated with ILD (OR [95% CI] 1.92 [1.03-3.59]; p = 0.039), age (OR [95% CI] 1.05 [1.01-1.08]; p = 0.004), CRP (OR [95% CI] 1.16 [1.05-1.29]; p = 0.003), and erosions (OR [95% CI] 1.05 [1.01-1.08]; p = 0.004); in the cases, it was associated with CRP (OR [95% CI] 1.17 [1.01-1.35]; p = 0.027), anti-citrullinated peptide antibody (OR [95% CI] 1.23 [1.14-13.02]; p = 0.049), and forced vital capacity (OR [95% CI] 0.79 [0.96-0.99]; p = 0.036).In patients with RA, multimorbidity was associated with ILD, systemic inflammation, and advanced age.

espanolObjetivo Revisar la eficacia y seguridad del rituximab en neuropatia vasculitica (NV). Metodos Se realizo una busqueda en la literatura de Medline y Embase hasta 2017. Los terminos incluidos guardaron relacion con «vasculitis», «neuropatia vasculitica» y «rituximab». Dicha busqueda fue realizada por 2 revisores. El resultado principal fue la eficacia del rituximab. Resultados Tras seleccionar inicialmente 702 articulos, 5 de ellos permanecieron con un nivel de evidencia de entre 1+ y 3, y un grado de recomendacion variable. En el unico ensayo clinico incluido, el rituximab fue superior a la terapia convencional para vasculitis crioglobulinemica, mostrando NV un incremento en la tasa de retencion farmacologica (64,3 vs. 3,5%; p Conclusiones Rituximab parece ser un tratamiento eficaz y seguro para NV, en el contexto de vasculitis crioglobulinemica. Se carece de evidencia sobre la eficacia especifica de NV en el contexto de otras vasculitis. EnglishObjective To review the efficacy and safety of rituximab in vasculitic neuropathy (VN). Methods A literature search was performed on Medline and Embase up until 2017. It included terms related to “vasculitis”,“vasculitic neuropathy” and “Rituximab”. Research was carried out by two reviewers. The main outcome was rituximab efficacy. Results Of an initial selection of 702 articles, 5 remained with a level of evidence between 1+ and 3 and variable recommendation degree. In the only clinical trial included, rituximab was superior to conventional therapy for cryoglobulinemic vasculitis with VN showing an increase in drug retention rate (64.3% vs. 3.5%; P Conclusions Rituximab seems an effective and safe treatment for VN in the context of cryoglobulinemic vasculitis. Evidence for specific efficacy in VN in the context of other types of vasculitis is lacking.

Rheumatoid arthritis (RA) is an immune-mediated inflammatory disease characterized by a defective adaptive immune receptor repertoire (AIRR) that fails to distinguish self from non-self antigens. The AIRR is vast, encompassing four T cell receptor (TCR) and three B cell receptor (BCR) chains, each of which displays an extraordinary amino acid sequence variability in the antigen-binding site. How the concerted action of T and B cell clones is associated with the development and clinical evolution of immune-mediated diseases is still not known. Using a new immunosequencing technology that allows the unbiased amplification of the seven receptor chains, we conducted an in-depth quantitative analysis of the seven-receptor chain variability in RA. Compared to healthy controls, the AIRR in RA was found to be characterized by a lower BCR diversity, the depletion of highly similar BCR clones, an isotype-specific signature as well as a skewed IGL chain and gene segment usage. A predictor based on quantitative multi-chain AIRR information was able to accurately predict disease, including the elusive seronegative subset of RA patients. AIRR features of the seven immune receptor chains were also different between patients with distinct clinically relevant phenotypes. Incorporating HLA variation data, we were able to identify the TCR clones that are specifically associated with the main disease risk variants. The longitudinal analysis of the AIRR revealed that treatment with Tumor Necrosis Factor (TNF) inhibitors selectively restores the diversity of B cell clones in RA patients by reducing the frequency of clones with a similar biochemical profile. The biochemical properties of the TNFi-modulated clones were also found to differ between responders and non-responders, supporting a different antigenic reactivity in the B cell compartment of these two groups of RA patients. Our comprehensive analysis of the TCR and BCR repertoire reveals a complex T and B cell architecture in RA, and provides the basis for precision medicine strategies based on the highly informative features of the adaptive immune response.

Resumen Objetivo Evaluar la efectividad y la seguridad de tocilizumab (TCZ) en pacientes con artritis reumatoide (AR) en practica clinica; la optimizacion de dosis y el cambio de formulacion intravenosa (iv) a subcutanea (sc). Material y metodos Estudio observacional retrospectivo. Se incluyo a 53 pacientes con AR tratados con TCZ. El desenlace principal fue efectividad de TCZ en la semana 24. Variables de desenlace secundarias incluyeron: efectividad en la semana 52, tiempo de retencion del tratamiento, funcion fisica y seguridad. Tambien se midio efectividad de la optimizacion de dosis y del cambio de formulacion iv a sc a los 3 y 6 meses. La efectividad se midio con el indice de actividad segun el Disease activity score-28. Se uso la prueba T pareada o prueba de rangos con signos de Wilcoxon para evaluar efectividad y el tiempo de supervivencia mediante curvas de Kaplan-Meier. Resultados La proporcion de pacientes que alcanzaron la remision o baja actividad de la enfermedad en las semanas 24 y 52 fue del 75,5 y el 87,3%, respectivamente. La media de tiempo de retencion (intervalo de confianza del 95% [IC del 95%]) fue de 81,7 meses (76,6-86,7). Veintiuno de 53 pacientes (39,6%) optimizaron la dosis de TCZ y 35 pacientes cambiaron a TCZ sc desde iv, sin cambios en resultados de efectividad. La tasa de efectos adversos fue 13,6 eventos/100 pacientes-ano. Conclusiones Tocilizumab parece efectivo y seguro en AR en practica clinica. La reduccion de dosis parece efectiva en la mayoria de los pacientes en remision, incluso cuando cambian de iv a sc. Objective To evaluate the effectiveness and safety of tocilizumab (TCZ) in patients with rheumatoid arthritis (RA) in clinical practice, establishing the optimized regimen and switching from intravenous (IV) to subcutaneous (SC) therapy. Material and methods Retrospective observational study. We included 53 RA patients treated with TCZ. The main outcome was TCZ effectiveness at week 24. Secondary outcome variables included effectiveness at week 52, therapeutic maintenance, physical function and safety. The effectiveness of optimization and the switch from IV to SC was evaluated at 3 and 6 months. The efficacy was measured with the Disease Activity Score. Paired t-tests or Wilcoxon were used to evaluate effectiveness and survival time using Kaplan-Meier. Results The proportion of patients who achieved remission or low disease activity at weeks 24 and 52 was 75.5% and 87.3%, respectively. The mean retention time (95% confidence interval [95% CI] was 81.7 months [76.6-86.7]). Twenty-one of 53 patients (39.6%) optimized the TCZ dose and 35 patients switched from IV TCZ to SC, with no changes in effectiveness. The adverse event rate was 13.6 events/100 patient-years. Conclusions Tocilizumab appears to be effective and safe in RA in clinical practice. The optimized regimen appears to be effective in most patients in remission, even when they change from IV to SC.

Objective To evaluate the effectiveness and safety of tocilizumab (TCZ) in patients with rheumatoid arthritis (RA) in clinical practice, establishing the optimised regimen and switching from intravenous (IV) to subcutaneous (SC) therapy. Material and methods Retrospective observational study. We included 53 RA patients treated with TCZ. The main outcome was TCZ effectiveness at week 24. Secondary outcome variables included effectiveness at week 52, therapeutic maintenance, physical function and safety. The effectiveness of optimization and the switch from IV to SC was evaluated at 3 and 6 months. The efficacy was measured with the Disease Activity Score. Paired t-tests or Wilcoxon were used to evaluate effectiveness and survival time using Kaplan–Meier. Results The proportion of patients who achieved remission or low disease activity at weeks 24 and 52 was 75.5% and 87.3%, respectively. The mean retention time (95% confidence interval [95% CI] was 81.7 months [76.6–86.7]). Twenty-one of 53 patients (39.6%) optimised the TCZ dose and 35 patients switched from IV TCZ to SC, with no changes in effectiveness. The adverse event rate was 13.6 events/100 patient-years. Conclusions Tocilizumab appears to be effective and safe in RA in clinical practice. The optimised regimen appears to be effective in most patients in remission, even when they change from IV to SC.

To establish a set of recommendations for the management of patients diagnosed with rheumatoid arthritis (RA) who cannot be treated with methotrexate (MTX) due to contraindications, drug toxicity or lack of adherence, and to establish therapeutic strategies more effective and safer in these RA patients. A qualitative analysis of the scientific evidence available to June 2015. The 2-round Delphi technique of consensus was used to collect and establish expert opinion based on the participants’ clinical experience when only low quality evidence was available. A total of 18 recommendations were developed for the management of this patient profile. Fourteen of these recommendations were related to drug safety aspects. Recommendations on contraindication and toxicity of MTX have been updated. The experts recommend the use of biological monotherapy, a preferred treatment option, in patients whose profiles reveal a contraindication, intolerance or circumstances that prevent us against the use of MTX. There is some high-quality scientific evidence that supports contraindication and establishes certain conditions of MTX use in RA patients with specific clinical profiles.

To establish a set of recommendations for the management of patients diagnosed with rheumatoid arthritis (RA) who cannot be treated with methotrexate (MTX) due to contraindications, drug toxicity or lack of adherence, and to establish therapeutic strategies more effective and safer in these RA patients. A qualitative analysis of the scientific evidence available to June 2015. The 2-round Delphi technique of consensus was used to collect and establish expert opinion based on the participants' clinical experience when only low quality evidence was available. A total of eighteen recommendations were developed for the management of this patient profile. Fourteen of these recommendations were related to drug safety aspects. Recommendations on contraindication and toxicity of MTX have been updated. The experts recommend the use of biological monotherapy, a preferred treatment option, in patients whose profiles reveal a contraindication, intolerance or circumstances that prevent us against the use of MTX. There is some high-quality scientific evidence that supports contraindication and establishes certain conditions of MTX use in RA patients with specific clinical profiles.

Background: The impact of chronic inflammatory rheumatic diseases on COVID-19 severity is poorly known. Here we compare the outcomes of a cohort of rheumatic patients with a matched control cohort to identify potential risk factors for severe illness. Methods: In this comparative cohort study, we systematically identified hospital PCR+ COVID-19 rheumatic patients with chronic inflammatory arthritis (IA) or autoimmune/immunomediated diseases (AI/IMID). Non-rheumatic controls were randomly sampled 1:1, and matched by age, sex, and PCR date. The main outcome was severe COVID-19, defined as death, invasive ventilation, ICU admission, or serious complications. We assessed the association between the outcome and potential prognostic variables, adjusted by COVID treatment, using logistic regression. Findings: The cohorts were composed of 456 rheumatic and non-rheumatic patients, in equal numbers. Mean age was 63 [IQR 53-78] and male sex 41% in both cohorts. Rheumatic diseases were IA (60%) and AI/IMID (40%). Patients were on treatment with glucocorticoids (40%), conventional synthetic disease modifying antirheumatic drugs (csDMARD) (57%), targeted synthetic or biological (ts/bDMARD) (23%), or other immunosuppressants (12%). Most patients (74%) had been hospitalised, and the risk of severe COVID was 31·6% in the rheumatic and 28·1% in the non-rheumatic cohort. Ageing, male sex and previous comorbidity (obesity, diabetes, hypertension, cardiovascular, or lung disease) increased the risk in the rheumatic cohort by bivariate analysis. In logistic regression analysis, independent factors associated with severe were increased age (OR 5·31; CI 3·14-8·95), male sex (2·13; CI 1·35-3·36) and having an AI/IMID (OR 1·98; CI 1·15-3·41). Interpretation: In patients with chronic inflammatory rheumatic diseases aging, sex and having an AI/IMID but not IA nor previous immunosuppressive therapies were associated with severe COVID-19. Funding Statement: The RIER network was supported by Fondo de Investigacion Sanitaria, Instituto de Salud Carlos III (RD16/0012 RETICS program) and cofinanced by the European Regional Development Fund. Declaration of Interests: None of the authors have competing interests to declare. Ethics Approval Statement: The study was approved by Comite de Etica de la Investigacion del Hospital Universitario 12 de Octubre, CEIm number: 20/160.

Resumen Introduccion En los ultimos anos, el peso especifico de las consultas externas ha aumentado considerablemente. En la actualidad, la mayor parte de la atencion reumatologica se lleva a cabo en esta area del hospital. Sin embargo, apenas existe documentacion respecto a estandares de calidad asistencial. Objetivo Desarrollar, mediante consenso, estandares de calidad asistencial especificos para las consultas externas de reumatologia. Metodo El proyecto se llevo a cabo mediante metodologia Delphi a 2 rondas. Se conto con la participacion de un comite cientifico (13 reumatologos), 5 grupos nominales (45 reumatologos y 12 enfermeras especializadas) y un grupo de discusion formado por 9 pacientes. Se generaron de forma sucesiva diversos borradores hasta obtener un documento final que incluyo los estandares que recibieron una puntuacion igual o superior a 7 en al menos el 70% de los participantes. Resultados El documento consta de 148 estandares distribuidos en 9 areas tematicas: a) estructura (22); b) actividad clinica y relacion con los pacientes (34); c) planificacion (7); d) niveles de prioridad (5); e) relacion con atencion primaria, con el servicio de urgencias y con otros servicios del hospital (20); f) proceso (26); g) enfermeria (13); h) docencia e investigacion (13), e i) computo de actividad (8). Conclusion Se han consensuado unos estandares de calidad asistencial que pueden ser utiles para organizar la actividad en las consultas externas de los servicios de reumatologia y servir como marco de referencia a la hora de elevar propuestas de mejora a la gerencia del hospital o a otros estamentos de la administracion.

Resumen Objetivo Evaluar la efectividad, seguridad y coste de rituximab en pacientes con artritis reumatoide (AR) dependiendo de la dosis utilizada. Material y metodos Estudio observacional retrospectivo. Se incluyo a 52 pacientes con AR tratados al menos con una dosis de rituximab durante 135,3 pacientes-ano. Se obtuvieron 3 grupos de tratamiento: G1, primer curso y siguientes de 2 infusiones de 1 g separadas 15 dias; G2, primer curso de 2 infusiones de 1 g seguido por cursos de 2 infusiones de 500 mg, y G3, primer curso y siguientes de 2 infusiones de 500 mg separadas por 15 dias. Los retratamientos fueron a demanda segun la clinica. Se analizaron por grupos: el tiempo retencion (Log-Rank), las tasas de retratamientos y de eventos adversos (razon de tasas de incidencia) y los costes del tratamiento por paciente-mes de rituximab. Resultados El grupo 2 mostro una mejor relacion coste-efectividad que el grupo 1 ya que se asocio a una mayor retencion de rituximab (media [IC del 95%] 65,7 [60,8-70,7] meses vs. 33,5 [22,7-44,3]; p Conclusiones El uso de rituximab a dosis completa al inicio seguido de dosis reducida en los sucesivos cursos administrados a demanda parece la opcion mas coste-efectiva.

Objective Evaluate the effectiveness, cost and safety of rituximab in patients with rheumatoid arthritis (RA) depending on the dose used. Material and methods Retrospective observational study conducted on 52 patients with RA treated with at least one dose of rituximab for 135.3 patient-years were included. Three treatment groups were obtained: (G1) First course and following two 1 g infusions separated by 15 days; (G2) First course 2 infusions of 1 g followed by 2 infusions of 500 mg; (G3) First course and followed by 2 infusions of 500 mg separated by 15 days. Re-treatments were administered on-demand according to the clinical activity. The retention time (Log-Rank), retreats and adverse events rates (incidence rate ratio) and treatment costs per patient-month of rituximab were analyzed by groups. Results Group 2 showed a better cost-effectiveness ratio than group 1, as it was associated with a longer retention of rituximab (mean [95% CI] 65.7 [60.8–70.7] months vs 33.5 [22.7–44.3]; P Conclusions The use of full-dose rituximab at onset, followed by reduced doses in successive courses administered on-demand retreatment may be the most cost-effective option.

Objetivo Establecer recomendaciones para el manejo de pacientes con artritis reumatoide (AR) centrado en el papel de los farmacos antirreumaticos modificadores de enfermedad (FAME) sinteticos y biologicos disponibles, que sirvan de referencia para todos los profesionales implicados en la atencion de estos pacientes. Metodos Las recomendaciones se consensuaron a traves de un panel de 14 expertos previamente seleccionados por la Sociedad Espanola de Reumatologia (SER). Se recogio la evidencia disponible mediante la actualizacion de las 3 revisiones sistematicas (RS) que se utilizaron para las recomendaciones EULAR 2013, a las que se anadio una nueva RS para dar respuesta a una pregunta adicional. Todas fueron realizadas por miembros del grupo de revisores de la SER. La clasificacion del nivel de la evidencia y del grado de la recomendacion se realizo utilizando el sistema del Centre for Evidence-Based Medicine de Oxford. Se utilizo la metodologia Delphi para evaluar el grado de acuerdo entre los panelistas para cada recomendacion. Resultados Se emiten un total de 13 recomendaciones sobre el manejo terapeutico de pacientes con AR del adulto. El objetivo terapeutico debe ser tratar al paciente en fases precoces de la enfermedad, con el objetivo de la remision clinica, teniendo un papel central el metotrexato como FAME sintetico de referencia. Se actualizan las indicaciones de los FAME biologicos disponibles, se enfatiza la importancia de los factores pronosticos y se incide en el concepto de optimizacion de biologicos. Conclusiones Se presenta la quinta actualizacion de las recomendaciones SER para el manejo de la AR con FAME sinteticos y biologicos.

Objectives To assess the efficacy and safety of golimumab in the 140 patients included in Spain as the first part of the GO-MORE trial, a multinational study involving patients with active rheumatoid arthritis (RA) despite treatment with different disease-modifying antirheumatic drugs (DMARDs). Patients and methods The patients received subcutaneous golimumab 50 mg once a month during 6 months. The primary endpoint was the percentage of individuals with a good or moderate EULAR DAS28-ESR response after 6 months of treatment. Results A total of 140 patients were included. Of these, 76.4% had very active disease (DAS28-ESR >5.1). 76.4% were taking methotrexate, 40.0% other DMARDs in monotherapy or combined, and 65.0% received corticosteroids. After 6 months, 82.9% of the patients showed a good or moderate EULAR response, 41.4% had low disease activity, and 30.7% were in remission. The percentage of responders one month after the first dose was 69.3%. The efficacy was similar in patients treated with methotrexate or other DMARDs, with different methotrexate doses, with or without corticosteroids, or in subjects who had failed one or more DMARDs. The response to golimumab was observed from the first dose. Golimumab was well tolerated and its safety profile was consistent with the findings of previous studies. Serious adverse events were reported in 11 patients (7.9%). Conclusion The addition of subcutaneous golimumab 50 mg once a month to different DMARDs in patients with active RA yielded a moderate or good response after 6 months in 82.9% of the cases. The response was observed early, from the start of the second month, after a single dose of golimumab.

Objective To analyse the efficacy and safety of rituximab in the treatment of non-renal systemic lupus erythematosus (SLE). Methods We systematically searched MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials up to June 2013. The following were the selection criteria: (1) adult patients with SLE, (2) rituximab treatment, (3) placebo or active comparator, (4) outcome measures assessing efficacy and/or (5) safety. Meta-analysis, systematic literature reviews, randomised control trials (RCT), open clinical trials and cohort studies were included. Independent extraction of articles by 2 authors using predefined data fields was performed. The quality of each study was graded using the Oxford Levels of Evidence and Jadad׳s scale. Results A total of 26 articles met our inclusion criteria: one RCT and its exploratory analysis, 2 open studies and 22 cohort studies, which analysed 1,231 patients. Overall, patients had active disease refractory to steroids and/or immunosuppressant drugs. Acceptable evidence suggested improvements in disease activity, arthritis, thrombocytopaenia, complement and anti-dsDNA, with a steroid-sparing effect. But relapses of disease were demonstrated too. Weak evidence suggested a response in anaemia, cutaneous and neuropsychiatric manifestations. Available evidence revealed few major adverse events. Studies had medium methodological quality and in general were applicable to current practice. Conclusion Rituximab has been shown to be safe and effective in the treatment of non-renal SLE, especially in terms of disease activity, immunologic parameters and steroid-sparing effect. However, it can only be recommended for organ-specific manifestations such as arthritis and thrombocytopaenia. High-quality studies are needed in order to consider the long-term effects of re-treatment on different organ-specific manifestations.

Objectives To analyze the Spanish experience in an international study which evaluated tocilizumab in patients with rheumatoid arthritis (RA) and an inadequate response to conventional disease-modifying antirheumatic drugs (DMARDs) or tumor necrosis factor inhibitors (TNFis) in a clinical practice setting. Material and methods Subanalysis of 170 patients with RA from Spain who participated in a phase IIIb, open-label, international clinical trial. Patients presented inadequate response to DMARDs or TNFis. They received 8 mg/kg of tocilizumab every 4 weeks in combination with a DMARD or as monotherapy during 20 weeks. Safety and efficacy of tocilizumab were analyzed. Special emphasis was placed on differences between failure to a DMARD or to a TNFi and the need to switch to tocilizumab with or without a washout period in patients who had previously received TNFi. Results The most common adverse events were infections (25%), increased total cholesterol (38%) and transaminases (15%). Five patients discontinued the study due to an adverse event. After six months of tocilizumab treatment, 71/50/30% of patients had ACR 20/50/70 responses, respectively. A higher proportion of TNFi-naive patients presented an ACR20 response: 76% compared to 64% in the TNFi group with previous washout and 66% in the TNFi group without previous washout. Conclusions Safety results were consistent with previous results in patients with RA and an inadequate response to DMARDs or TNFis. Tocilizumab is more effective in patients who did not respond to conventional DMARDs than in patients who did not respond to TNFis.

Resumen Objetivos Analizar la experiencia espanola en un estudio internacional para evaluar tocilizumab en pacientes con artritis reumatoide (AR) con respuesta insuficiente al tratamiento con farmacos antirreumaticos modificadores de la enfermedad convencionales (FAME) o anti-TNF en condiciones cercanas a la practica clinica habitual. Material y metodos Subanalisis de 170 pacientes con AR que participaron en Espana en un ensayo clinico, internacional abierto de fase iii b, que presentaban una respuesta inadecuada al tratamiento con FAME o anti-TNF. Los pacientes recibieron 8 mg/kg de tocilizumab cada 4 semanas en combinacion con FAME o en monoterapia durante un periodo de 20 semanas. Se evaluaron la seguridad y la eficacia de tocilizumab distinguiendo entre pacientes con fallo a FAME o anti-TNF y, dentro de estos, entre los que habian hecho o no periodo de lavado del anti-TNF. Resultados Los acontecimientos adversos mas frecuentes fueron infecciones (25%) y elevacion de colesterol total (38%) y transaminasas (15%). Cinco pacientes abandonaron el estudio por un acontecimiento adverso. El 71/50/30% de los pacientes cumplia criterios de respuesta ACR 20/50/70 a los 6 meses del inicio del tratamiento con tocilizumab. Los pacientes naive para anti-TNF presentaron una mayor respuesta ACR20: el 76% frente a un 64% en el grupo anti-TNF con lavado previo y el 66% en el grupo anti-TNF sin lavado previo. Conclusiones Se confirma el perfil de seguridad de tocilizumab en pacientes con AR y fallo a FAME o anti-TNF. Tocilizumab es mas eficaz en pacientes que no responden de forma satisfactoria al tratamiento con FAME convencionales que con anti-TNF.

a b s t r a c t Objective: To determine the incidence and prevalence of cancer in a cohort of patients with systemic lupus erythematosus (SLE) and identify associated risk factors. Patients and methods: The study comprised a dynamic cohort of SLE patients (November 1989 to Decem- ber 2006) at a tertiary referral centre. An adjusted external control from the hospital tumour registry was used. Results: The study included 175 SLE patients (90% women), with a mean time at risk of 1370.5 patient- years. Fourteen women (8%) died, mainly from cardiovascular events. No patient died due to malignancy. We found 35 tumours in 28 patients, 25 of them after the diagnosis of SLE, of which 5 were malignant. The rate of benign tumours was 14.6/1000 patient-years (95% CI, 8.9-22.5) and of malignant tumours 3.6/1000 patient-years (95% CI, 1.5-8.8), with a crude incidence odds ratio for malignant tumours of 3.5 (95% CI, 1.5-7.9). However, this significance was lost after standardizing the rates. Concerning associated risk factors, differences were found in the mean erythrocyte sedimentation rate (HR 1.4 (1.1-1.7)), and the presence of thrombosis (HR 6.9 (1.49-41.2)), especially arterial thrombosis. Conclusions: We found a crude incidence rate of cancer that was almost four times greater in our SLE patients as compared with the expected rate in the hospital area of western Malaga.

Objective To provide a reference to rheumatologists and other physicians involved in the treatment of systemic lupus erythematosus (SLE) who are using, or about to use biologic therapies. Methods Recommendations were developed following a nominal group methodology and based on systematic reviews. The level of evidence and degree of recommendation were classified according to a model proposed by the Center for Evidence Based Medicine at Oxford. The level of agreement was established through a Delphi technique. Results We have produced recommendations on the use of belimumab, the only biological agent with approved indications for SLE, and other biological agents without an indication for SLE. The objective of treatment is to achieve a complete clinical response, taken as the absence of perceived or evident disease activity. Nuances regarding the use of biologic therapies in SLE were reviewed as well, such as the evaluation that should be performed prior to administration and the follow up of patients undergoing these therapies. Conclusions We present the SER recommendations for the use of biological therapies in patients with SLE.

Objetivo Elaborar unas recomendaciones que sirvan de referencia a los reumatologos y otros profesionales implicados en el tratamiento del lupus eritematoso sistemico (LES) que vayan a utilizar o consideren la utilizacion de terapias biologicas en su manejo. Metodos Las recomendaciones se emitieron siguiendo la metodologia de grupos nominales y basadas en revisiones sistematicas. El nivel de evidencia y el grado de recomendacion se clasificaron segun el modelo del Center for Evidence Based Medicine de Oxford y el grado de acuerdo se extrajo por tecnica Delphi. Resultados Se realizan recomendaciones sobre el uso de belimumab, actualmente unica terapia biologica con aprobacion para el tratamiento del LES, y otras terapias biologicas sin indicacion aprobada en LES. El objetivo del tratamiento es la respuesta clinica completa, entendida como la ausencia de actividad clinica percibida o constatable. Se matiza el uso de terapias biologicas en LES y cual debe ser la evaluacion previa y la vigilancia del paciente que recibe estos farmacos. Conclusiones Se presentan las recomendaciones SER sobre el uso de terapias biologicas en el LES.

Aim To determine whether rheumatoid arthritis (RA) patients who have been prescribed biological agents exhibit a different comorbidity burden than RA patients who take disease-modifying antirheumatic drugs (DMARDs) alone, and to understand the association between comorbidity and other variables, as well as the association between comorbidity and multimorbidity. Methods This observational case–control study included 114 RA patients treated with biological agents and a control group comprising 163 sex- and age-matched RA patients treated with DMARDs only. Current and previous data regarding the patients’ disease activity, comorbidities, and treatments were collected. The data were analysed using bivariate and multivariate regression models. Results The patients who were prescribed biological agents exhibited poorer disease control, received more DMARDs and steroids, and underwent more total joint arthroplasties compared with the patients in the control group. However, the risk factors for cardiovascular disease and the comorbidity frequency were similar between cases and controls. The most prevalent comorbidities were hypertension, obesity, and respiratory, thyroid, and upper gastrointestinal disorders. The incidence of cardiovascular disease was low, and only 29% of the patients exhibited multimorbidities. A bivariate association of age, late diagnosis, joint replacements and a high score on the health assessment questionnaire score (HAQ) with comorbidity was observed. There were also correlations between the Charlson index and age, joint reconstructive surgery, disease activity (DAS28), and HAQ score. However, when binary logarithmic regression models were applied, only patient age remained significantly associated with comorbidity and multimorbidity [hazard ratio, 1.08; 95% confidence interval, 1.05–1.12; p Conclusion RA patients taking biological drugs have a comorbidity burden equivalent to those treated with DMARDs alone. Age is the main predictive factor of comorbidity in these patients.

Objetivo Conocer el numero anual y la tendencia de las protesis implantadas en nuestro hospital a los pacientes con artritis reumatoide (AR) durante la ultima decada. Material y metodos Estudio observacional retrospectivo. Los pacientes fueron localizados mediante busqueda exhaustiva en la base de datos del servicio de documentacion clinica entre 1998 y 2007. Los datos se extrajeron de las historias clinicas siguiendo un cuestionario predisenado. El analisis estadistico longitudinal de las protesis colocadas se efectuo mediante la Q de Cochrane y las curvas de Kaplan-Meier. Resultado Sesenta y un pacientes con AR fueron intervenidos con 78 protesis como consecuencia directa de su enfermedad en nuestro hospital entre 1998 y 2007. La mayoria eran mujeres (80%) con factor reumatoide positivo (84%). La media de edad fue de 58 anos y el tiempo de evolucion medio de la AR fue de 13 anos. Todos excepto uno habian recibido previamente farmacos antirreumaticos (88% metotrexato), pero solo el 11% habia accedido a una terapia biologica. No se observaron cambios en el numero de artroplastias a lo largo de toda la decada, aunque si hubo una tendencia a la reduccion en el numero de pacientes que precisaron por primera vez una protesis de rodilla (Q Cochrane; p=0,05). Conclusion No hemos observado cambios significativos en la colocacion de protesis articulares en su conjunto en la ultima decada en nuestro hospital, aunque podria estar produciendose un descenso del numero de pacientes que acceden por primera vez a una protesis de rodilla.

Objective To determine the annual number and trend of prostheses implanted in patients with rheumatoid arthritis (RA) at our hospital during the past decade. Materials and methods Retrospective observational study. Patients were collected through an extensive search of the database of the Clinical Documentation Service between 1998 and 2007. The data were extracted from medical records using a predesigned questionnaire. Statistical analysis of longitudinal prostheses was made using Cochrane's Q test and the Kaplan–Meier method. Results Sixty-one RA patients were operated on with 78 prostheses as a direct result of their disease at our hospital between 1998 and 2007. Most were women (80%) with positive rheumatoid factor (84%). The mean age was 58 years, and the average time since onset of RA was 13 years. All but one had previously received antirheumatic drugs (88% methotrexate), but only 11% had biological therapy. No changes were observed in the number of arthroplasties as a whole over a decade, although there was a trend toward reduction in the number of patients that required a knee replacement for the first time (Cochrane Q , P =.05). Conclusion We observed no significant changes in trends in the number of new joint replacement procedures as a whole in the past decade at our hospital, although the number of patients who required knee replacement for the first time as a direct result of their underlying disease seems to have declined in the last decade.

Systemic lupus erythematosus is an autoimmune disease that may involve the function of organs and reduce the survival of patients. Advances in the diagnosis and treatment have improved the short-term prognosis.However, most therapeutic improvements come from progress in other areas of medicine and only in recent years is this trend changing. Unfortunately, the development of new drugs for lupus is facing specific difficulties and the development of rituximab in lupus has been stopped despite good results in the observational studies. This review examines some of the aspects that influence these difficulties from the perspective of the LESIMAB database.

Objective To evaluate the effectiveness and safety of anti-tumor necrosis factor therapy in patients with amyloid A amyloidosis. Methods Multicenter, controlled, dynamic prospective cohort study of 36 patients with amyloid A amyloidosis (94% kidney involvement) treated with anti-tumor necrosis factor agents (drug exposure of 102.97 patient-years). As an external control group, 35 propensity score-matched non-amyloid patients were chosen from the Base de Datos de Productos Biologicos de la Sociedad Espanola de Reumatologia registry. The end points were kidney response and progression, anti-tumor necrosis factor continuation rate, patient survival, and adverse events. Results At the end of follow-up, a kidney response was observed in 12 of 22 patients (54.5%) and a kidney progression was observed in 6 of 36 patients (17%). The kidney amyloidosis remained stable in 16 of 36 patients (44%). The level of acute phase reactants diminished but did not reach the normal level. The continuation rates of anti-tumor necrosis factor drugs among patients with amyloid A amyloidosis after 1, 2, 3, and 4 or more years were 80%, 80%, 61%, and 52%, respectively, comparable to controls. The 5-year cumulative survival of amyloid A amyloidosis cases was 90.6%, and the 10-year survival was 78.5%. In a multivariate Cox regression analysis, the duration of amyloidosis and the level of proteinuria at the onset of anti-tumor necrosis factor treatment were independent predictors of treatment failure, whereas the level of proteinuria was the only factor that predicts mortality. Most adverse events were similar in both groups, although the number of infections was 3 times higher in amyloid A amyloidosis cases. Conclusion Anti-tumor necrosis factor drugs are effective in treating amyloid A amyloidosis, although they might increase the risk of infection.

Fundamento y objetivo: Describir y comparar las caracteristicas demograficas, clinicas y analiticas de una serie de casos de sindrome antifosfolipidico (SAF; criterios de Harris) primarios y secundarios atendidos en 2 centros espanoles de referencia. Pacientes y metodo: Se describen 112 pacientes con SAF ?en 50 casos primario (SAFP) y en 62 secundario (SAFS)?, de los que 56 (90%) presentaban lupus eritematoso sistemico, controlados en los 2 centros de referencia de la provincia de Malaga entre 1989 y 2000. Los datos se recogieron de las historias por los clinicos responsables mediante un protocolo preestablecido. Resultados: La edad en el momento del estudio fue similar en ambos grupos (42,3 [14,7] anos para el grupo total). Los pacientes con SAFS comenzaron su enfermedad mas jovenes (29,6 [12,6] frente a 37,0 [13,9] anos en el SAFP) y tuvieron mayor tiempo de evolucion de la enfermedad (143,3 [115,5] frente a 83,5 [73,5] meses en el SAFP). Hubo un predominio de sexo femenino (un 84% en el SAFS y un 60% en el SAFP). La prevalencia de fenomenos tromboticos arteriales (43%) y venosos (39%), perdidas fetales (40%), parto prematuro (9%), anticuerpos anticardiolipina (88%) y anticoagulante lupico (54%) fueron similares en ambos grupos. El SAFS presento mayor prevalencia de anticuerpos antinucleares, trombocitopenia y anemia hemolitica. Conclusiones: Los pacientes con SAFP y SAFS no presentan diferencias en las manifestaciones clinicas ni en las alteraciones inmunologicas caracteristicas del sindrome. Los pacientes con SAFS son mas jovenes al comienzo de su enfermedad y tienen mayor predominio del sexo femenino. Nuestros pacientes difieren de los de otras series espanolas publicadas, lo que se explica por la existencia de sesgos de seleccion y clasificacion.

Studies have shown that the survival of patients with lupus nephritis (LN) who receive a transplant has results similar to those of nondiabetic control subjects.The aim of this study was to evaluate the survival of lupus patients who received a transplant at our center, and to determine risk factors for mortality and graft loss.This case-control (1:2) study comprised patients with chronic kidney disease secondary to LN who received a kidney transplant (n = 32) in the Malaga area from 1985 to 2010. The controls subjects (n = 64) were matched by age, sex, and transplant period. We analyzed graft and patient survivals and risk factors compared with long-term transplant patients without LN.No differences were found in the variables analyzed between groups, except for the most frequent cause of donor death, which was almost significant: stroke in LN and traumatic brain injury in control subjects (P = .05). of the whole study sample, 45% lost the graft, primarily owing to chronic kidney disease (53.5%), followed by vascular thrombosis (16.3%); P = .57. Censored graft losses occurred in 63% of the patients transplanted before 2000, whereas it occurred in 20% of those transplanted after 2000 (P.001). Censored graft survival was similar between the groups throughout the followup, as was patient survival. Cox regression showed that only acute rejection was associated with a 2-fold increased risk of graft loss.Our lupus transplant population showed no differences in graft or patient survival compared with control subjects. Those patients who received a transplant from 2000 had better results, which may be related to several factors, such as immunosuppression, correction of cardiovascular conditions, or other factors. Risk factors for death and graft loss were similar to the control population.