Effects of COVID-19 vaccination on disease activity in patients with rheumatoid arthritis and psoriatic arthritis on targeted therapy in the COVIDSER study.

OBJECTIVE: To investigate the influence of COVID-19 vaccination on disease activity in rheumatoid arthritis (RA) and psoriatic arthritis (PsA) patients under targeted therapies. PATIENTS AND METHODS: 1765 vaccinated patients COVID-19, 1178 (66.7%) with RA and 587 (33.3%) with PsA from the COVID-19 registry in patients with rheumatic diseases (COVIDSER) project, were included. Demographics, disease characteristics, Disease Activity Score in 28 joints (DAS28) and targeted treatments were collected. DAS28-based flare rates and categorised disease activity distribution prevaccination and post vaccination were analysed by log-linear regression and contingency analyses, respectively. The influence of vaccination on DAS28 variation as a continuous measure was evaluated using a random coefficient model. RESULTS: The distribution of categorised disease activity and flare rates was not significantly modified by vaccination. Log-linear regression showed no significant changes in the rate of flares in the 6-month period after vaccination compared with the same period prior to vaccination in neither patients with RA nor patients with PsA. When DAS28 variations were analysed using random coefficient models, no significant variations in disease activity were detected after vaccination for both groups of patients. However, patients with RA treated with Janus kinase inhibitors (JAK-i) (1) and interleukin-6 inhibitor (IL-6-i) experienced a worsening of disease activity (1.436±0.531, p=0.007, and 1.201±0.550, p=0.029, respectively) in comparison with those treated with tumour necrosis factor inhibitor (TNF-i). Similarly, patients with PsA treated with interleukin-12/23 inhibitor (IL-12/23-i) showed a worsening of disease activity (4.476±1.906, p=0.019) compared with those treated with TNF-i. CONCLUSION: COVID-19 vaccination was not associated with increased rate of flares in patients with RA and PsA. However, a potential increase in disease activity in patients with RA treated with JAK-i and IL-6-i and in patients with PsA treated with IL-12/23-i warrants further investigation.

Infección tuberculosa de localización infrecuente / Tuberculosis infection in an unusual location

No disponible

Objetivos y metodología de la fase III de BIOBADASER / Objectives and methodology of BIOBADASER phase III

Objetivo: Describir los objetivos, la metodología y los resultados del primer año de la nueva versión del registro español de acontecimientos adversos de terapias biológicas y fármacos sintéticos con diana identificable en enfermedades reumáticas (BIOBADASER III). Metodología: Registro prospectivo multicéntrico de pacientes con enfermedades inflamatorias reumáticas en tratamiento con terapia biológica o fármacos sintéticos con diana identificable y atendidos en servicios de Reumatología en España. El objetivo principal de BIOBADASER Fase III es la recogida y análisis de acontecimientos adversos al que se ha añadido como objetivo secundario la evaluación de la efectividad mediante la recogida de índices de actividad. Los pacientes que entran en el registro son evaluados al menos una vez cada año y cada vez que presenten un acontecimiento adverso o se produzcan modificaciones en el tratamiento. La recogida de datos de la fase iii se inició el 17 de diciembre del 2015. Resultados: Durante el primer año han participado 35 centros. El número de pacientes incluidos en esta nueva fase en diciembre del 2016 era de 2.664. La edad media era de 53,7 años, con una mediana de duración de la enfermedad hasta el inicio de tratamiento de 8,1 años. Un 40,4% de los pacientes estaban diagnosticados de artritis reumatoide. Los acontecimientos adversos más frecuentes eran las infecciones e infestaciones. Conclusiones: La fase iii de BIOBADASER se ha puesto en marcha para responder a un entorno farmacológico cambiante con la aparición de los biosimilares y las pequeñas moléculas en el tratamiento de la patología reumática. Esta nueva etapa se adapta a los cambios normativos en la comunicación de acontecimientos adversos y amplía la información recogida incluyendo los índices de actividad

Objective: Describe the objectives, methods and results of the first year of the new version of the Spanish registry of adverse events involving biological therapies and synthetic drugs with an identifiable target in rheumatic diseases (BIOBADASER III). Methodology: Multicenter prospective registry of patients with rheumatic inflammatory diseases being treated with biological drugs or synthetic drugs with an identifiable target in rheumatology departments in Spain. The main objective of BIOBADASER Phase III is the registry and analysis of adverse events; moreover, a secondary objective was added consisting of assessing the effectiveness by means of the registry of activity indexes. Patients in the registry are evaluated at least once every year and whenever they experience an adverse event or a change in treatment. The collection of data for phase iii began on 17 December 2015. Results: During the first year, 35 centers participated. The number of patients included in this new phase in December 2016 was 2,664. The mean age was 53.7 years and the median duration of treatment was 8.1 years. In all, 40.4% of the patients were diagnosed with rheumatoid arthritis. The most frequent adverse events were infections and infestations. Conclusions: BIOBADASER Phase III has been launched to adapt to a changing pharmacological environment, with the introduction of biosimilars and small molecules in the treatment of rheumatic diseases. This new stage is adapted to the changes in the reporting of adverse events and now includes information related to activity scores

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

Objectives and methodology of BIOBADASER phase iii. / Objetivos y metodología de la fase iii de BIOBADASER.

OBJECTIVE: Describe the objectives, methods and results of the first year of the new version of the Spanish registry of adverse events involving biological therapies and synthetic drugs with an identifiable target in rheumatic diseases (BIOBADASER III). METHODOLOGY: Multicenter prospective registry of patients with rheumatic inflammatory diseases being treated with biological drugs or synthetic drugs with an identifiable target in rheumatology departments in Spain. The main objective of BIOBADASER Phase III is the registry and analysis of adverse events; moreover, a secondary objective was added consisting of assessing the effectiveness by means of the registry of activity indexes. Patients in the registry are evaluated at least once every year and whenever they experience an adverse event or a change in treatment. The collection of data for phase iii began on 17 December 2015. RESULTS: During the first year, 35 centers participated. The number of patients included in this new phase in December 2016 was 2,664. The mean age was 53.7 years and the median duration of treatment was 8.1 years. In all, 40.4% of the patients were diagnosed with rheumatoid arthritis. The most frequent adverse events were infections and infestations. CONCLUSIONS: BIOBADASER Phase III has been launched to adapt to a changing pharmacological environment, with the introduction of biosimilars and small molecules in the treatment of rheumatic diseases. This new stage is adapted to the changes in the reporting of adverse events and now includes information related to activity scores.

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.

Persistence and adverse events of biological treatment in adult patients with juvenile idiopathic arthritis: results from BIOBADASER.

BACKGROUND: Biologic therapy has changed the prognosis of patients with juvenile idiopathic arthritis (JIA). The aim of this study was to examine the pattern of use, drug survival, and adverse events of biologics in patients with JIA during the period from diagnosis to adulthood. METHODS: All patients included in BIOBADASER (Spanish Registry for Adverse Events of Biological Therapy in Rheumatic Diseases), a multicenter prospective registry, diagnosed with JIA between 2000 and 2015 were analyzed. Proportions, means, and SDs were used to describe the population. Incidence rates and 95% CIs were calculated to assess adverse events. Kaplan-Meier analysis was used to compare the drug survival rates. RESULTS: A total of 469 patients (46.1% women) were included. Their mean age at diagnosis was 9.4 ± 5.3 years. Their mean age at biologic treatment initiation was 23.9 ± 13.9 years. The pattern of use of biologics during their pediatric years showed a linear increase from 24% in 2000 to 65% in 2014. Biologic withdrawal for disease remission was higher in patients who initiated use biologics prior to 16 years of age than in those who were older (25.7% vs 7.9%, p < 0.0001). Serious adverse events had a total incidence rate of 41.4 (35.2-48.7) of 1000 patient-years. Patients younger than 16 years old showed significantly increased infections (p < 0.001). CONCLUSIONS: Survival and suspension by remission of biologics were higher when these compounds were initiated in patients with JIA who had not yet reached 16 years of age. The incidence rate of serious adverse events in pediatric vs adult patients with JIA treated with biologics was similar; however, a significant increase of infection was observed in patients under 16 years old.

Estudio VARIAR: valoración de la eficacia y seguridad a corto plazo en artritis reumatoide del uso de RItuximab comparado con Antagonistas del factor de necrosis tumoral alfa en segunda línea terapéutica en pacientes con artritis reumatoide Refractarios a un primer antagonista del factor de necrosis tumoral alfa / VARIAR Study: assessment of short-term efficacy and safety of rituximab compared to an tumor necrosis factor alpha antagonists as second-line drug therapy in patients with rheumatoid arthritis refractory to a first tumor necrosis factor alpha antagonist

Objetivo. Evaluar la eficacia y la seguridad a corto plazo del tratamiento de pacientes con artritis reumatoide (AR) con rituximab (RTX) comparado con un anti-TNF (2TNF) tras retirada de un primer anti-TNF. Métodos. Estudio multicéntrico prospectivo, observacional, de práctica clínica de pacientes con AR grave refractaria a anti-TNF que recibieron RTX comparados con los que recibieron un 2TNF. Comparación de las variables de eficacia y respuesta EULAR buena/moderada a los 6 meses. Resultados. Ciento tres pacientes incluidos; 82 alcanzan seguimiento a 6 meses, 73,7% mujeres. Datos basales grupo RTX y 2TNF, respectivamente: 8,6 y 6,6 NAD, 8,8 y 7,5 NAI, 5,45 ± 1,28 y 5,18 ± 1,21 en DAS28 (p=0,048), 41 y 38,7mmHg de VSG, y 1,2 y 1,0 en HAQ. Mejoría en todos los parámetros en ambos grupos sin diferencias significativas (excepto mayor reducción de VSG con RTX). Ausencia de efectos adversos graves. Conclusiones. El uso de RTX en segunda línea de terapia biológica tras fallo a un primer anti-TNF en práctica clínica muestra mejoría en las variables de eficacia y funcionalidad a los 6 meses, sin presentar efectos adversos graves. Estos resultados no difieren de los observados tras el uso de un segundo anti-TNF en el mismo escenario clínico (AU)

Objective. to compare the short-term efficacy and safety of rituximab (RTX) therapy versus anti-TNF in rheumatoid arthritis (RA) patients after discontinuation of a first anti-TNF agent. Methods. prospective observational multicenter study in the clinical practice setting, involving patients with severe RA refractory to a first anti-TNF agent, who received either RTX or a second anti-TNF (2TNF), comparing the efficacy endpoints, EULAR response (Good/Moderate) and safety at 6 months. Results. 103 patients enrolled, 82 completed 6-month follow-up, 73.7% women. Baseline data for RTX and 2TNF groups, respectively: TJC, 8.6 and 6.6; SJC, 8.8 and 7.5; DAS28 score, 5.45 (±1.28) and 5.18 (±1.21) (p=0.048), ESR, 41 and 38.7mmHg; and HAQ, 1.2 and 1.0. Improvement was observed in all parameters, with no significant differences (except for a more marked reduction in ESR with RTX). There were no serious adverse events. Conclusions. RTX use as second-line therapy after anti-TNF failure led to improvements in the efficacy and functional variables at 6 months, with no serious adverse events. These results were comparable to those observed in patients who used a second anti-TNF agent in the same clinical scenario (AU)

VARIAR Study: Assessment of short-term efficacy and safety of rituximab compared to an tumor necrosis factor alpha antagonists as second-line drug therapy in patients with rheumatoid arthritis refractory to a first tumor necrosis factor alpha antagonist. / Estudio VARIAR: VAloración de la eficacia y seguridad a corto plazo en artritis reumatoide del uso de RItuximab comparado con Antagonistas del factor de necrosis tumoral alfa en segunda línea terapéutica en pacientes con artritis reumatoide Refractarios a un primer antagonista del factor de necrosis tumoral alfa.

OBJECTIVE: to compare the short-term efficacy and safety of rituximab (RTX) therapy versus anti-TNF in rheumatoid arthritis (RA) patients after discontinuation of a first anti-TNF agent. METHODS: prospective observational multicenter study in the clinical practice setting, involving patients with severe RA refractory to a first anti-TNF agent, who received either RTX or a second anti-TNF (2TNF), comparing the efficacy endpoints, EULAR response (Good/Moderate) and safety at 6 months. RESULTS: 103 patients enrolled, 82 completed 6-month follow-up, 73.7% women. Baseline data for RTX and 2TNF groups, respectively: TJC, 8.6 and 6.6; SJC, 8.8 and 7.5; DAS28 score, 5.45 (±1.28) and 5.18 (±1.21) (p=0.048), ESR, 41 and 38.7mmHg; and HAQ, 1.2 and 1.0. Improvement was observed in all parameters, with no significant differences (except for a more marked reduction in ESR with RTX). There were no serious adverse events. CONCLUSIONS: RTX use as second-line therapy after anti-TNF failure led to improvements in the efficacy and functional variables at 6 months, with no serious adverse events. These results were comparable to those observed in patients who used a second anti-TNF agent in the same clinical scenario.

Efficacy of tocilizumab in conventional treatment-refractory adult-onset Still's disease: multicenter retrospective open-label study of thirty-four patients.

OBJECTIVE: Adult-onset Still's disease (AOSD) is frequently refractory to standard therapy. Tocilizumab (TCZ) has demonstrated efficacy in single cases and in small series of patients with AOSD. The aim of this multicenter study was to assess the efficacy of TCZ in patients with AOSD refractory to conventional treatment. METHODS: This was a retrospective open-label study of TCZ treatment in 34 patients with AOSD who had experienced an inadequate response to corticosteroids and at least 1 standard synthetic immunosuppressive drug and also, in many cases, biologic agents. RESULTS: The mean ± SD age of the patients (8 men and 26 women) was 38.7 ± 16.1 years. The median duration of AOSD before TCZ was initiated was 4.2 years (interquartile range [IQR] 1-9 years). The initial dosages of intravenous TCZ were 8 mg/kg every 4 weeks in 22 patients, 4 mg/kg every 4 weeks in 2 patients, and 8 mg/kg every 2 weeks in 10 patients. TCZ treatment resulted in rapid and maintained improvement in both clinical and laboratory parameters. After 1 year of TCZ therapy, the incidence of joint manifestations had decreased from 97.1% at baseline to 32.4%, the incidence of both cutaneous manifestations and fever had decreased from 58.8% to 5.9%, and the incidence of lymphadenopathy had decreased from 29.4% to 0%. A dramatic reduction in laboratory markers of inflammation, including the C-reactive protein level, the erythrocyte sedimentation rate, and the ferritin level, was achieved. The median dosage of prednisone was also reduced, from 13.8 mg/day (IQR 5-45) at the initiation of TCZ to 2.5 mg/day (IQR 0-30) at 12 months. After a median followup of 19 months (IQR 12-31 months), only 2 patients required permanent discontinuation of TCZ therapy because of severe infections. CONCLUSION: TCZ treatment was associated with rapid and maintained clinical and laboratory improvement in patients with AOSD refractory to standard treatment. However, joint manifestations seem to be more refractory to treatment compared with systemic manifestations.

Comparative effectiveness of switching to alternative tumour necrosis factor (TNF) antagonists versus switching to rituximab in patients with rheumatoid arthritis who failed previous TNF antagonists: the MIRAR Study.

OBJECTIVE: To compare the effectiveness of switching to rituximab (RTX) with switching to alternative tumour necrosis factor (TNF) antagonists in patients with rheumatoid arthritis (RA) failing on TNF antagonists. METHODS: A multicentre prospective 3-year observational study was performed in patients with RA treated with RTX or an alternative TNF antagonist. The baseline 28-joint disease activity score (DAS28) and Health Assessment Questionnaire (HAQ) score were compared with 6, 9 and 12 month values, adjusting for propensity score quintiles. Propensity scores were estimated for each patient using logistic regression with treatment as the dependent variable and baseline prior number of TNFs >1, years from diagnosis >5, extra-articular manifestations, previous toxicity, use of ≥2 disease-modifying antirheumatic drugs, age and sex as independent variables. RESULTS: 1124 patients were treated with either RTX (n=591, 52.6%) or alternative TNF antagonists (n=533, 47.4%). RTX-treated patients had longer disease duration (p=0.0001), larger numbers of previous TNF antagonists (p<0.0001) and tender and swollen joints (p<0.0001). There was no significant difference in the reduction in DAS28 at 6, 9 and 12 months between RTX-treated patients and those treated with TNF antagonists. However, the reduction in DAS28 was significantly different between RTX-treated patients and adalimumab/infliximab-treated patients (p=0.001 and p=0.05, respectively). There was a marginally significant difference at any time period in the proportion of patients achieving an improvement in the HAQ score of >0.22 (p=0.06). CONCLUSIONS: Optimal treatment for patients with RA failing on treatment with TNF antagonists may include RTX. This study suggests that the improvement in DAS28 is larger in patients treated with RTX than in those treated with monoclonal anti-TNF agents.

Incidence and risk of hospitalisation due to shingles and chickenpox in patients with rheumatic diseases treated with TNF antagonists.

OBJECTIVE: To estimate the incidence of hospitalisation due to varicella zoster virus (VZV) infection in patients treated with tumour necrosis factor (TNF) antagonists for inflammatory rheumatic conditions and to compare it with the expected rate in the general population. METHODS: Secondary data analysis was performed of two large databases: (1) the national registry of rheumatic diseases patients treated with biological agents (BIOBADASER); and (2) the national hospital discharge database Conjunto Mínimo Básico de Datos al Alta Hospitalaria. Hospitalisations due to shingles or chickenpox were analysed. For each condition the incidence rate (IR) and the age and gender standardised IR per 100,000 person-years plus the standardised incidence ratio (SIR) and the standardised incidence difference (SID) were estimated. RESULTS: In patients exposed to TNF antagonists, the estimated IR of hospitalisation due to shingles was 32 cases per 100,000 patient-years (95% CI 14 to 78), the expected rate in the general population was 3.4 (95% CI 3.2 to 3.5), the SIR was 9 (95% CI 3 to 20) and the SID was 26 (95% CI 14 to 37). The estimated IR of hospitalisation due to chickenpox was 26 cases per 100,000 (95% CI 10 to 69), the expected rate was 1.9 (95% CI 1.8 to 2.0), the SIR was 19 (95% CI 5 to 47) and the SID 33 (95% CI 21 to 45). CONCLUSIONS: Patients suffering rheumatic diseases exposed to TNF antagonists are hospitalised due to VZV infections significantly more frequently than expected in the general population. Since the absolute IR of hospitalisations due to chickenpox and shingles is low in these patients, the implementation of risky preventive measures may not be justified at present.