Real-world apremilast use in biologic-naïve psoriatic arthritis patients. Data from Spanish clinical practice / Uso real de apremilast en pacientes con artritis psoriásica sin tratamiento biológico. Datos de la práctica clínica española

Introduction: Apremilast is approved for treatment of psoriasis and psoriatic arthritis (PsA). Real-world evidence on apremilast effectiveness in clinical practice is limited. Methods: Observational study enrolling adult patients, across 21 Spanish centres, who had initiated apremilast in the prior 6 (±1) months and were biologic naive. Data were collected at routine follow-up visits 6 and 12 months after apremilast initiation. Primary outcome was 6 and 12-month persistence to apremilast. Secondary outcomes included Disease Activity for PsA (DAPSA), joint erosions, enthesitis, dactylitis, and patient-reported quality of life (QoL, measured using the PsA impact of disease [PsAID] questionnaire). Results: We included 59 patients. Most had oligoarticular PsA, moderate disease activity, and high comorbidity burden. Three-quarters were continuing apremilast at 6 months and two-thirds at 12 months; mean (SD) apremilast treatment duration was 9.43 (1.75) months. DAPSA scores showed improved disease activity: one-third of patients in remission or low activity at apremilast initiation versus 62% and 78% at 6 and 12 months, respectively. Eleven of 46 patients with radiographic assessments had joint erosions at apremilast initiation and none at month 12. Median (Q1, Q3) number of swollen joints was 4.0 (2.0, 6.0) at apremilast initiation versus 0.0 (0.0, 2.0) at 12 months. Incidence of dactylitis and enthesitis decreased between apremilast initiation (35.6% and 28.8%, respectively) and month 12 (11.6% and 2.4%, respectively). Over two-thirds of patients had a PSAID-9 score <4 (cut-off for patient-acceptable symptom state) at month 12. Conclusions: In Spanish clinical practice, two-thirds of PsA patients continued apremilast at 12 months, with clinical benefits at the joint level, no radiographic progression of erosions, and a positive impact on patient-reported QoL.(AU)

Introducción: Apremilast está aprobado para el tratamiento de la psoriasis y la artritis psoriásica (APs). La evidencia sobre la efectividad de apremilast en la práctica clínica es limitada. Métodos: Estudio observacional en el que se incluyó a pacientes adultos, de 21 centros españoles, que habían iniciado apremilast en los 6 (± 1) meses previos y no habían recibido biológicos. Los datos se recogieron en visitas rutinarias de seguimiento a los 6 y 12 meses del inicio de apremilast. El objetivo primario fue la persistencia de apremilast a los 6 y 12 meses. Los objetivos secundarios incluyeron la actividad de la enfermedad para APs (DAPSA), erosiones articulares, entesitis, dactilitis y la calidad de vida informada por el paciente (CdV, medida mediante el cuestionario “PsA Impact of disease [PsAID]”). Resultados: Se incluyó a 59 pacientes. La mayoría presentaba APs oligoarticular, actividad moderada de la enfermedad y alta comorbilidad. Tres cuartas partes continuaban con apremilast a los 6 meses y 2 tercios a los 12 meses; la duración media (DE) del tratamiento con apremilast fue de 9,43 (1,75) meses. Las puntuaciones DAPSA mostraron una mejora de la actividad de la enfermedad: un tercio de los pacientes en remisión o baja actividad al inicio de apremilast frente al 62 y el 78% a los 6 y 12 meses, respectivamente. Once de 46 pacientes con evaluaciones radiográficas presentaban erosiones articulares al inicio de apremilast y ninguno en el mes 12. La mediana (Q1, Q3) del número de articulaciones inflamadas fue de 4,0 (2,0, 6,0) al inicio de apremilast frente a 0,0 (0,0, 2,0) a los 12 meses. La incidencia de dactilitis y la entesitis disminuyeron entre el inicio de apremilast (el 35,6 y el 28,8%, respectivamente) y el mes 12 (el 11,6 y el 2,4%, respectivamente). Más de 2 tercios de los pacientes tenían una puntuación PSAID-9 < 4 (punto de corte del estado sintomático aceptable para el paciente) en el mes 12.(AU)

Real-world apremilast use in biologic-naïve psoriatic arthritis patients. Data from Spanish clinical practice.

INTRODUCTION: Apremilast is approved for treatment of psoriasis and psoriatic arthritis (PsA). Real-world evidence on apremilast effectiveness in clinical practice is limited. METHODS: Observational study enrolling adult patients, across 21 Spanish centres, who had initiated apremilast in the prior 6 (±1) months and were biologic naive. Data were collected at routine follow-up visits 6 and 12 months after apremilast initiation. Primary outcome was 6 and 12-month persistence to apremilast. Secondary outcomes included Disease Activity for PsA (DAPSA), joint erosions, enthesitis, dactylitis, and patient-reported quality of life (QoL, measured using the PsA impact of disease [PsAID] questionnaire). RESULTS: We included 59 patients. Most had oligoarticular PsA, moderate disease activity, and high comorbidity burden. Three-quarters were continuing apremilast at 6 months and two-thirds at 12 months; mean (SD) apremilast treatment duration was 9.43 (1.75) months. DAPSA scores showed improved disease activity: one-third of patients in remission or low activity at apremilast initiation versus 62% and 78% at 6 and 12 months, respectively. Eleven of 46 patients with radiographic assessments had joint erosions at apremilast initiation and none at month 12. Median (Q1, Q3) number of swollen joints was 4.0 (2.0, 6.0) at apremilast initiation versus 0.0 (0.0, 2.0) at 12 months. Incidence of dactylitis and enthesitis decreased between apremilast initiation (35.6% and 28.8%, respectively) and month 12 (11.6% and 2.4%, respectively). Over two-thirds of patients had a PSAID-9 score <4 (cut-off for patient-acceptable symptom state) at month 12. CONCLUSIONS: In Spanish clinical practice, two-thirds of PsA patients continued apremilast at 12 months, with clinical benefits at the joint level, no radiographic progression of erosions, and a positive impact on patient-reported QoL. Trial registration number Clinicaltrials.gov: NCT03828045.

Pharmacogenetic Sex-Specific Effects of Methotrexate Response in Patients with Rheumatoid Arthritis.

Methotrexate (MTX) is a commonly used drug for the treatment of rheumatoid arthritis (RA), but its effectiveness can vary greatly among patients. Pharmacogenetics, the study of how genetic variations can affect drug response, has the potential to improve the personalized treatment of RA by identifying genetic markers that can predict a patient's response to MTX. However, the field of MTX pharmacogenetics is still in its early stages and there is a lack of consistency among studies. This study aimed to identify genetic markers associated with MTX efficacy and toxicity in a large sample of RA patients, and to investigate the role of clinical covariates and sex-specific effects. Our results have identified an association of ITPA rs1127354 and ABCB1 rs1045642 with response to MTX, polymorphisms of FPGS rs1544105, GGH rs1800909, and MTHFR genes with disease remission, GGH rs1800909 and MTHFR rs1801131 polymorphisms with all adverse events, and ADA rs244076 and MTHFR rs1801131 and rs1801133, However, clinical covariates were more important factors to consider when building predictive models. These findings highlight the potential of pharmacogenetics to improve personalized treatment of RA, but also emphasize the need for further research to fully understand the complex mechanisms involved.

Recommendations for prevention of infection in systemic autoimmune rheumatic diseases.

OBJECTIVES: To develop recommendations for the prevention of infection in adult patients with systemic autoimmune rheumatic diseases (SARD). METHODS: Clinical research questions relevant to the objective of the document were identified by a panel of experts selected based on their experience in the field. Systematic reviews of the available evidence were conducted, and evidence was graded according to the Scottish Intercollegiate Guidelines Network criteria. Specific recommendations were made. RESULTS: Five questions were selected, referring to prevention of infection by Pneumocystis jirovecii with trimethoprim/sulfamethoxazole, primary and secondary prophylactic measures against hepatitis B virus, vaccination against human papillomavirus, vaccination against Streptococcus pneumoniae and vaccination against influenza virus, making a total of 18 recommendations, structured by question, based on the evidence found for the different SARD and/or expert consensus. CONCLUSIONS: There is enough evidence on the safety and efficacy of vaccinations and other prophylactic measures against the microorganisms reviewed in this document to specifically recommend them for patients with SARD.

Systematic review of the impact of drugs on diffuse interstitial lung disease associated with rheumatoid arthritis.

OBJECTIVE: To review the available evidence on the impact of rheumatoid arthritis (RA) treatments in associated diffuse interstitial lung disease (ILD). METHODS: Systematic review of studies evaluating the impact of pharmacological treatment in patients with RA and ILD. A bibliographic search in MEDLINE, EMBASE and Cochrane, a selection of articles and the methodological quality assessment (FLC 3.0 OSTEBA) and grading of the level of evidence (SING) of the selected articles were performed. RESULTS: 1,720 references were identified in primary search and 7 in manual or indirect. Forty-three articles were included: 7 systematic reviews, 2 randomized clinical trials, 5 cohort studies, 8 case-control studies and 21 case series. Methotrexate (MTX) and leflunomide (LEF) do not increase incidence, complications or mortality due to ILD. Although the results are not uniform, anti-TNF have often had worse outcomes in incidence, progression and mortality due to ILD than MTX, LEF, abatacept (ABA) and rituximab (RTX). The evidence found is scarce for JAK kinase and antifibrotic inhibitors, and controversial for IL-6 inhibitors. CONCLUSIONS: There is no evidence that MTX or LEF worsens the prognosis of patients with AR-EPID. RTX and ABA seem to have better results than other biologicals, such us TNFi, often achieving stabilization and, in some cases, the improvement of ILD in patients with RA.

Revisión sistemática sobre el impacto de los fármacos en la enfermedad pulmonar intersticial difusa asociada a Artritis Reumatoide / Systematic Review of the Impact of Drugs on Diffuse Interstitial Lung Disease Associated with Rheumatoid Arthritis

Objetivo: Revisar la evidencia disponible sobre la repercusión de los tratamientos de la artritis reumatoide (AR) en la enfermedad pulmonar intersticial difusa (EPID) asociada. Métodos: Revisión sistemática de estudios que evalúan el impacto del tratamiento farmacológico en pacientes con AR y EPID. Se realizó una búsqueda bibliográfica en MEDLINE, EMBASE y Cochrane, selección de artículos y evaluación de la calidad metodológica (FLC 3.0 OSTEBA) y graduación del nivel de evidencia (SING). Resultados: Se identificaron 1.720 referencias en búsqueda primaria y 7 en manual o indirecta. Se incluyeron 43 artículos: 7 revisiones sistemáticas, 2 ensayos clínicos aleatorizados, 5 estudios de cohortes, 8 estudios de casos-controles y 21 series de casos. Metotrexato (MTX) y leflunomida (LEF) no aumentan la incidencia, complicaciones ni mortalidad por EPID. Aunque los resultados no son uniformes, los anti-TNF han tenido con frecuencia peores resultados en incidencia, progresión y mortalidad por EPID que MTX, LEF, abatacept (ABA) y rituximab (RTX). La evidencia encontrada es escasa para los inhibidores de JAK quinasas y antifibróticos, y controvertida para los inhibidores de la IL-6. Conclusiones: No existe evidencia de que MTX o LEF empeoren el pronóstico de los pacientes con AR-EPID. RTX y ABA parecen tener mejores resultados que otros biológicos, como anti-TNF, consiguiendo con frecuencia la estabilización y, en algunos casos, la mejoría de la EPID en pacientes con AR.(AU)

Objective: To review the available evidence on the impact of rheumatoid arthritis (RA) treatments in associated diffuse interstitial lung disease (ILD). Methods: Systematic review of studies evaluating the impact of pharmacological treatment in patients with RA and ILD. A bibliographic search in MEDLINE, EMBASE and Cochrane, a selection of articles and the methodological quality assessment (FLC 3.0 OSTEBA) and grading of the level of evidence (SING) of the selected articles were performed. Results: 1,720 references were identified in primary search and 7 in manual or indirect. Forty-three articles were included: 7 systematic reviews, 2 randomized clinical trials, 5 cohort studies, 8 case-control studies and 21 case series. Methotrexate (MTX) and leflunomide (LEF) do not increase incidence, complications or mortality due to ILD. Although the results are not uniform, anti-TNF have often had worse outcomes in incidence, progression and mortality due to ILD than MTX, LEF, abatacept (ABA) and rituximab (RTX). The evidence found is scarce for JAK kinase and antifibrotic inhibitors, and controversial for IL-6 inhibitors. Conclusions: There is no evidence that MTX or LEF worsens the prognosis of patients with AR-EPID. RTX and ABA seem to have better results than other biologicals, such as anti-TNF, often achieving stabilization and, in some cases, the improvement of ILD in patients with RA.(AU)

Recommendations for prevention of infection in systemic autoimmune rheumatic diseases. / Recomendaciones SER sobre prevención de infección en enfermedades reumáticas autoinmunes sistémicas.

OBJECTIVES: To develop recommendations for the prevention of infection in adult patients with systemic autoimmune rheumatic diseases (SARD). METHODS: Clinical research questions relevant to the objective of the document were identified by a panel of experts selected based on their experience in the field. Systematic reviews of the available evidence were conducted, and evidence was graded according to the Scottish Intercollegiate Guidelines Network criteria. Specific recommendations were made. RESULTS: Five questions were selected, referring to prevention of infection by Pneumocystis jirovecii with trimethoprim/sulfamethoxazole, primary and secondary prophylactic measures against hepatitis B virus, vaccination against human papillomavirus, vaccination against Streptococcus pneumoniae and vaccination against influenza virus, making a total of 18 recommendations, structured by question, based on the evidence found for the different SARD and/or expert consensus. CONCLUSIONS: There is enough evidence on the safety and efficacy of vaccinations and other prophylactic measures against the microorganisms reviewed in this document to specifically recommend them for patients with SARD.

Sarcopenia, immune-mediated rheumatic diseases, and nutritional interventions.

INTRODUCTION: Sarcopenia is defined by a loss of muscle mass and function associated with mortality, decreased physical performance, falls, and disability. Since chronic inflammation and decreased physical activity are risk factors for developing sarcopenia, it is critical to assess the role of sarcopenia in immune-mediated rheumatic diseases (IMRDs). Moreover, nutritional interventions are emerging as key modifiable and affordable options to improve physical performance in sarcopenia. OBJECTIVE: The aim of this review is to critically summarize current information on the evidence linking nutritional interventions and sarcopenia in IMRDs. METHODS: The search and selection of articles was performed in Medline, Dimensions.ai, Google Scholar, Cochrane Library, Epistemonikos, and Trip Database. The results were clustered into three areas: sarcopenia and IMRDs, sarcopenia and biological disease-modifying antirheumatic drugs (bDMARDs), and nutritional interventions for sarcopenia. FINDINGS: Several cross-sectional studies have shown a higher prevalence of sarcopenia in IMRDs, such as rheumatoid arthritis. Although not fully established, evidence linking sarcopenia and other IMRDs (ankylosing spondylitis and systemic sclerosis) has been also described. For secondary sarcopenia prevention and treatment, bDMARDs' administration proved efficacy in patients with rheumatoid arthritis. Furthermore, there is growing evidence linking nutrition to the prevention and treatment of sarcopenia. Evidence linking unfavourable results in nutritional risk assessment, insufficient intake of protein, vitamin D, antioxidant nutrients, and long-chain polyunsaturated fatty acids and sarcopenia have been reported. CONCLUSION: Given that sarcopenia and IMRDs have strong links, further research is needed to improve patient care.

Cardiovascular mortality and cardiovascular event rates in patients with inflammatory rheumatic diseases in the CARdiovascular in rheuMAtology (CARMA) prospective study-results at 5 years of follow-up.

OBJECTIVES: To determine cardiovascular (CV) mortality and incidence of the first CV event (CVE) in patients with chronic inflammatory rheumatic diseases (CIRD) after 5 years of follow-up. METHODS: This is an analysis of the CARdiovascular in rheMAatology (CARMA) study after 5 years of follow-up. It includes patients with RA (n = 775), AS (n = 738) and PsA (n = 721), and individuals without CIRD (n = 677) attending outpatient rheumatology clinics from 67 public hospitals in Spain. Descriptive analyses were performed for the CV mortality at 5 years. The Systematic COronary Risk Evaluation (SCORE) function at 5 years was calculated to determine the expected risk of CV mortality. Poisson models were used to estimate the incidence rates of the first CVE. Hazard ratios of the risk factors involved in the development of the first CVE were evaluated using the Weibull proportional hazard model. RESULTS: Overall, 2382 subjects completed the follow-up visit at 5 years. Fifteen patients died due to CVE. CV deaths observed in the CIRD cohort were lower than that predicted by SCORE risk charts. The highest incidence rate of CVE [7.39 cases per 1000 person-years (95% CI 4.63, 11.18)] was found in PsA patients. However, after adjusting for age, sex and CV risk factors, AS was the inflammatory disease more commonly associated with CVE at 5 years [hazard ratio 4.60 (P =0.02)], compared with those without CIRD. CONCLUSIONS: Cardiovascular mortality in patients with CIRD at 5 years of follow-up is lower than estimated. Patients with AS have a higher risk of developing a first CVE after 5 years of follow-up.

Systematic Review of the Impact of Drugs on Diffuse Interstitial Lung Disease Associated with Rheumatoid Arthritis. / Revisión sistemática sobre el impacto de los fármacos en la enfermedad pulmonar intersticial difusa asociada a Artritis Reumatoide.

OBJECTIVE: To review the available evidence on the impact of rheumatoid arthritis (RA) treatments in associated diffuse interstitial lung disease (ILD). METHODS: Systematic review of studies evaluating the impact of pharmacological treatment in patients with RA and ILD. A bibliographic search in MEDLINE, EMBASE and Cochrane, a selection of articles and the methodological quality assessment (FLC 3.0 OSTEBA) and grading of the level of evidence (SING) of the selected articles were performed. RESULTS: 1,720 references were identified in primary search and 7 in manual or indirect. Forty-three articles were included: 7 systematic reviews, 2 randomized clinical trials, 5 cohort studies, 8 case-control studies and 21 case series. Methotrexate (MTX) and leflunomide (LEF) do not increase incidence, complications or mortality due to ILD. Although the results are not uniform, anti-TNF have often had worse outcomes in incidence, progression and mortality due to ILD than MTX, LEF, abatacept (ABA) and rituximab (RTX). The evidence found is scarce for JAK kinase and antifibrotic inhibitors, and controversial for IL-6 inhibitors. CONCLUSIONS: There is no evidence that MTX or LEF worsens the prognosis of patients with AR-EPID. RTX and ABA seem to have better results than other biologicals, such as anti-TNF, often achieving stabilization and, in some cases, the improvement of ILD in patients with RA.

Indicador compuesto para evaluar la calidad asistencial en el manejo de los pacientes con artritis reumatoide en las consultas externas de Reumatología / A composite indicator to assess the quality of care in the management of patients with rheumatoid arthritis in outpatient rheumatology clinics

Objetivo: El paradigma actual en el tratamiento de la artritis reumatoide (AR) contempla el diagnóstico temprano y el uso precoz de fármacos modificadores de enfermedad (FAME) para alcanzar la remisión o baja actividad inflamatoria, lo cual, se conoce como «treat to target» (T2T). El objetivo del trabajo es desarrollar un indicador compuesto (IC) para evaluar la calidad asistencial en el manejo de los pacientes con AR atendiendo a la estrategia T2T y a otras recomendaciones generales para la atención de estos pacientes. Material y método: La construcción del IC siguió las fases: 1) selección de los criterios de calidad mediante un juicio de expertos; 2) priorización de los criterios, a partir de un Delphi con 20 expertos; 3) diseño de los indicadores de calidad, y 4) cálculo del IC ponderado. La fuente de información para el cálculo del IC son las historias clínicas de los pacientes con AR. Resultados: De los 37 criterios seleccionados, 12 necesitaron una segunda ronda Delphi. Se priorizaron 31 criterios, los cuales presentaron una mediana en relevancia y factibilidad, en las rondas Delphi, mayor o igual a 7,5, con un rango intercuartílico inferior a 3,5, y un grado de acuerdo (puntuación mayor o igual a 8) igual o superior al 80%. Conclusiones: El IC construido, consensuado y ponderado, permite evaluar la calidad asistencial de los pacientes con AR, en las Unidades de Reumatología de hospitales españoles, ofreciendo una medida resumen válida y fácilmente interpretable

Objective: The current guidelines in the treatment of rheumatoid arthritis (RA) include the early diagnosis and early use of disease modifying drugs to achieve remission or low disease activity level, known as "Treat to Target" (T2T). The objective of this study is to develop a composite indicator (CI) to evaluate the quality of care in the management of patients with RA, according to the T2T strategy and other general recommendations concerning the management of these patients. Material and method: The phases of the construction of the CI were: 1) selection of quality criteria through expert judgment; 2) prioritization of the criteria, according to relevance and feasibility, applying the Delphi methodology (two rounds) involving 20 experts; 3) design of quality indicators; and 4) calculation of the weighted CI, using the mean value in relevance and feasibility granted by the experts. The source of information for the calculation of the CI are the medical records of patients with RA. Results: Twelve criteria out of 37 required a second Delphi round. Thirty-one criteria were prioritized. These criteria presented a median in relevance and feasibility greater than or equal to 7.5, with an interquartile range of less than 3.5, and a level of agreement (score greater than or equal to 8) greater than or equal to 80%. Conclusions: The constructed CI allows us to evaluate the quality of care of patients with RA following the T2T strategy in the rheumatology units of Spanish hospitals, offering a valid and easily interpretable summary measure

A composite indicator to assess the quality of care in the management of patients with rheumatoid arthritis in outpatient rheumatology clinics. / Indicador compuesto para evaluar la calidad asistencial en el manejo de los pacientes con artritis reumatoide en las consultas externas de Reumatología.

OBJECTIVE: The current guidelines in the treatment of rheumatoid arthritis (RA) include the early diagnosis and early use of disease modifying drugs to achieve remission or low disease activity level, known as "Treat to Target" (T2T). The objective of this study is to develop a composite indicator (CI) to evaluate the quality of care in the management of patients with RA, according to the T2T strategy and other general recommendations concerning the management of these patients. MATERIAL AND METHOD: The phases of the construction of the CI were: 1) selection of quality criteria through expert judgment; 2) prioritization of the criteria, according to relevance and feasibility, applying the Delphi methodology (two rounds) involving 20 experts; 3) design of quality indicators; and 4) calculation of the weighted CI, using the mean value in relevance and feasibility granted by the experts. The source of information for the calculation of the CI are the medical records of patients with RA. RESULTS: Twelve criteria out of 37 required a second Delphi round. Thirty-one criteria were prioritized. These criteria presented a median in relevance and feasibility greater than or equal to 7.5, with an interquartile range of less than 3.5, and a level of agreement (score greater than or equal to 8) greater than or equal to 80%. CONCLUSIONS: The constructed CI allows us to evaluate the quality of care of patients with RA following the T2T strategy in the rheumatology units of Spanish hospitals, offering a valid and easily interpretable summary measure.

Atributos del fármaco antirreumático modificador de la enfermedad biológico en las primeras líneas de tratamiento de la artritis reumatoide. Proyecto ACORDAR 2015 / Biologic Disease-modifying antirheumatic drug attributes in the first lines of treatment of rheumatoid arthritis. 2015 ACORDAR Project

Objetivo. Existen pacientes con artritis reumatoide (AR) que no responden de la forma deseada a la terapia biológica. Nuestro objetivo fue reconocer los atributos del FAME biológico (FAMEb) que podrían identificar al más adecuado en las primeras líneas de tratamiento de la AR. Métodos. Para reconocer los atributos que podrían definir el FAMEb, se realizó una búsqueda sistemática de la literatura acerca de aspectos generales, farmacología, eficacia, seguridad, administración y coste. A continuación, se realizó un proceso Delphi a 2 rondas entre un grupo de reumatólogos expertos en el manejo de la AR para determinar el grado de acuerdo con los atributos identificados, indicando el grado de importancia que se le daba a cada atributo. Se aplicaron 2 criterios para determinar la consistencia de los resultados: 1) sobre la base de la mediana y el rango intercuartílico, y 2) el cumplimiento simultáneo de media, mediana, desviación estándar, rango intercuartílico y coeficiente de variación. Se determinaron también la concordancia y la ratificación final del panel de expertos. Resultados. Ochenta y tres reumatólogos españoles completaron las 2 circulaciones del proceso Delphi. Ninguno de los 77 atributos identificados se consideró de baja importancia, 75 de los 77 (97,4%) se consideraron de alta importancia y 76 de los 77 (98,7%) fueron ratificados. Quince tuvieron el apoyo del 100% del grupo de trabajo. Conclusiones. Quince atributos tuvieron el apoyo del 100% del grupo de trabajo y podrían considerarse los que definirían el FAMEb ideal en las primeras líneas de tratamiento de la AR (AU)

Objective. To date, between 17% and 35% of patients with rheumatoid arthritis (RA) do not respond as expected to the initial biological therapy. The objective of this project is to recognize and weigh the attributes of biologic DMARD (bDMARD) to identify the most appropriate for each case, in the first lines of treatment of RA (after inadequate response to at least one synthetic DMARD or previous bDMARD). Methods. To recognize the possible attributes that could define the bDMARD, we performed a systematic search of the literature that recognized the possible attributes involving general aspects, pharmacology, efficacy, safety, management, and cost. Then a Delphi process was conducted with two rounds among a group of selected expert rheumatologists in the management of RA indicating the degree of agreement with the attributes identified in the literature. The project was completed between February and September 2015, indicating the degree of importance that was ascribed to each attribute. Two criteria were applied to determine the consistency of results: 1) based on the median and interquartile range; and 2) on the simultaneous compliance with mean, median, standard deviation, interquartile range and coefficient of variation. The agreement and final ratification of the expert panel were also determined. Results. Eighty-three Spanish rheumatologists participated and completed both rounds of the Delphi process. In no case was the importance of the 77 attributes identified considered to be low; 75 of 77 (97.4%) were considered highly important and 76 of 77 (98.7%) were ratified. Fifteen attributes had the support of 100% of the working group. Conclusions. There was a high degree of agreement concerning the selected attributes. Fifteen of them had the support of 100% of the working group and could be considered the definition of the ideal bDMARD in the first lines of RA treatment (AU)

Biologic Disease-modifying antirheumatic drug attributes in the first lines of treatment of rheumatoid arthritis. 2015 ACORDAR project. / Atributos del fármaco antirreumático modificador de la enfermedad biológico en las primeras líneas de tratamiento de la artritis reumatoide. Proyecto ACORDAR 2015.

OBJECTIVE: To date, between 17% and 35% of patients with rheumatoid arthritis (RA) do not respond as expected to the initial biological therapy. The objective of this project is to recognize and weigh the attributes of biologic DMARD (bDMARD) to identify the most appropriate for each case, in the first lines of treatment of RA (after inadequate response to at least one synthetic DMARD or previous bDMARD). METHODS: To recognize the possible attributes that could define the bDMARD, we performed a systematic search of the literature that recognized the possible attributes involving general aspects, pharmacology, efficacy, safety, management, and cost. Then a Delphi process was conducted with two rounds among a group of selected expert rheumatologists in the management of RA indicating the degree of agreement with the attributes identified in the literature. The project was completed between February and September 2015, indicating the degree of importance that was ascribed to each attribute. Two criteria were applied to determine the consistency of results: 1) based on the median and interquartile range; and 2) on the simultaneous compliance with mean, median, standard deviation, interquartile range and coefficient of variation. The agreement and final ratification of the expert panel were also determined. RESULTS: Eighty-three Spanish rheumatologists participated and completed both rounds of the Delphi process. In no case was the importance of the 77 attributes identified considered to be low; 75 of 77 (97.4%) were considered highly important and 76 of 77 (98.7%) were ratified. Fifteen attributes had the support of 100% of the working group. CONCLUSIONS: There was a high degree of agreement concerning the selected attributes. Fifteen of them had the support of 100% of the working group and could be considered the definition of the ideal bDMARD in the first lines of RA treatment.

Lipoprotein(a) concentrations in rheumatoid arthritis on biologic therapy: Results from the CARdiovascular in rheuMAtology study project.

BACKGROUND: Plasma concentrations of lipoprotein (a) (Lp(a)), a lipoprotein with atherogenic and thrombogenic properties, have a strong genetic basis, although high concentrations of Lp(a) have also been reported in the context of inflammation, as in rheumatoid arthritis (RA). Few studies evaluate the impact of biologic therapies (BT) on Lp(a) in RA, taking into account that with these new therapies a better control of inflammation is achieved. OBJECTIVE: The aim of the study was to evaluate the plasma concentrations of Lp(a) in Spanish RA patients on BT attending rheumatology outpatient clinics. METHODS: Baseline analysis of the CARdiovascular in rheuMAtology project, a 10-year prospective study, evaluating the risk of cardiovascular events in RA and other forms of inflammatory arthritis. RA patients were classified according to treatment: no biologic, anti-tumor necrosis factor, anti-interleukin-6 receptor tocilizumab (TCZ), and other biologic (rituximab or abatacept). A model of linear multivariate regression was built in which the dependent variable was Lp(a) concentration and the explanatory variable was BT. The model was adjusted for confounding factors. RESULTS: Seven hundred and seventy-five RA patients were analyzed. Plasma concentrations of total cholesterol and triglyceride were significantly higher in TCZ-treated patients. Nevertheless, no significant difference in the atherogenic index between TCZ-treated patients and patients without BT was found. After adjusting for confounding factors, patients with BT had lower concentrations of Lp(a) than those without BT; however, only TCZ-treated patients achieved statistically significant differences (ß: -0.303, 95% confidence interval: -0.558 to -0.047; P = .02). CONCLUSIONS: RA patients treated with TCZ show lower plasma concentrations of Lp(a) compared with patients without BT.

Fracturas vertebrales múltiples en varón joven como primera manifestación de una mastocitosis sistémica / Multiple vertebral fractures in young man as first manifestation of systemic mastocytosis

La mastocitosis sistémica (MS) es una enfermedad clonal de los progenitores mastocíticos de la médula ósea. El cuadro clínico varía desde una forma asintomática (indolente) hasta una forma altamente agresiva con una supervivencia muy corta (leucemia de mastocitos). Un 28-34% de los pacientes con MS tiene síntomas relacionados con la afección ósea en el momento del diagnóstico y el 16% fracturas. La presentación de MS como fracturas vertebrales clínicas en varones jóvenes no es frecuente. A continuación describimos un caso de osteoporosis establecida como única manifestación de MS (AU)

Systemic mastocytosis (SM) is a clonal disease of mast cell progenitors from the bone marrow. The clinical picture varies from asymptomatic forms (indolent) to a highly aggressive form with a very short (mast cell leukemia) survival. Between 28-34% of patients with SM are related to bone condition at the time of diagnosis and 16% have symptomatic fractures. The presentation of SM as clinical vertebral fractures in young men is rare. Here, we describe a case of established osteoporosis as the only manifestation of SM (AU)

Multiple vertebral fractures in young man as first manifestation of systemic mastocytosis. / Fracturas vertebrales múltiples en varón joven como primera manifestación de una mastocitosis sistémica.

Systemic mastocytosis (SM) is a clonal disease of mast cell progenitors from the bone marrow. The clinical picture varies from asymptomatic forms (indolent) to a highly aggressive form with a very short (mast cell leukemia) survival. Between 28-34% of patients with SM are related to bone condition at the time of diagnosis and 16% have symptomatic fractures. The presentation of SM as clinical vertebral fractures in young men is rare. Here, we describe a case of established osteoporosis as the only manifestation of SM.