Sublingual Bacterial Vaccination Reduces Recurrent Infections in Patients With Autoimmune Diseases Under Immunosuppressant Treatment.

Introduction: Conventional or biologic disease-modifying anti-rheumatic drugs (DMARDs) are the mainstay of treatment for systemic autoimmune disease (SAD). Infectious complications are a major concern in their use. Objective: To evaluate the clinical benefit of sublingual mucosal polybacterial vaccines (MV130 and MV140), used to prevent recurrent respiratory and urinary tract infections, in patients with SAD and secondary recurrent infections following conventional or biologic DMARDs. Methods: An observational study in SAD patients with recurrent respiratory tract infections (RRTI) and/or recurrent urinary tract infections (RUTI) was carried out. All patients underwent mucosal (sublingual) vaccination with MV130 for RRTI or with MV140 for RUTI daily for 3 months. Clinical evaluation was assessed during 12 months of follow-up after the first dose, i.e., 3 months under treatment and 9 months once discontinued, and compared with the previous year. Results: Forty-one out of 55 patients completed 1-year follow-up. All patients were on either conventional or biologic DMARDs. A significant decrease in the frequency of RUTI (p<0.001), lower respiratory tract infections (LRTI) (p=0.009) and upper respiratory tract infections (URTI) (p=0.006) at 12-mo with respect to the previous year was observed. Antibiotic prescriptions and unscheduled medical visits decreased significantly (p<0.020) in all groups. Hospitalization rate also declined in patients with RRTI (p=0.019). The clinical benefit demonstrated was concomitant to a significant increase in both anti-S. pneumoniae IgA and IgG antibodies following MV130 vaccination. Conclusions: Sublingual polybacterial vaccines prevent recurrent infections in patients with SAD under treatment with immunosuppressant therapies, supporting a broad non-specific anti-infectious effect in these patients.

Recomendaciones para el uso de la ecografía y la resonancia magnética en pacientes con artritis reumatoide / Recommendations for the use of ultrasound and magnetic resonance in patients with rheumatoid arthritis

Objetivo. Establecer recomendaciones, basadas en la evidencia, sobre el uso de la ecografía (US) y la resonancia magnética (RM) en pacientes con artritis reumatoide (AR). Métodos. Las recomendaciones se consensuaron mediante metodología basada en grupos nominales. Un grupo de expertos (15 reumatólogos y 3 radiólogos) definió el alcance, usuarios, apartados del documento, posibles recomendaciones, revisiones sistemáticas a realizar (se utilizaron y actualizaron las revisiones de documentos de consenso previos de EULAR), y de la asignación de tareas. Los expertos delimitaron los apartados y redactaron las recomendaciones. El nivel de evidencia y grado de recomendación se realizó utilizando el sistema del Center for Evidence Based Medicine de Oxford. El grado de acuerdo se estableció mediante un Delphi a 2 rondas. Las recomendaciones se votaron según una escala de 1 (total desacuerdo) a 10 (total acuerdo), definiéndose el acuerdo como una puntuación ≥ 7 por al menos el 70% de los participantes. El documento completo fue revisado por los expertos y el proyecto coordinado por un metodólogo experto. Resultados. Se emitieron 20 recomendaciones que cubren: la validez de la US y RM para la detección de actividad y daño estructural, capacidad diagnóstica, predictora (de progresión de daño estructural, de brote de la enfermedad, respuesta al tratamiento, etc.), utilidad en la evaluación y monitorización de estos pacientes que están en tratamiento, y uso de la US como guía (para infiltraciones o biopsias). Conclusiones. Se presentan recomendaciones útiles para el manejo de la US y RM por los clínicos en pacientes con AR (AU)

Objective. To develop evidence-based recommendations on the use of ultrasound (US) and magnetic resonance imaging (MRI) in patients with rheumatoid arthritis (RA). Methods. Recommendations were generated following a nominal group technique. A panel of experts, consisting of 15 rheumatologists and 3 radiologists, was established in the first panel meeting to define the scope and purpose of the consensus document, as well as chapters, potential recommendations and systematic literature reviews (we used and updated those from previous EULAR documents). A first draft of recommendations and text was generated. Then, an electronic Delphi process (2 rounds) was carried out. Recommendations were voted from 1 (total disagreement) to 10 (total agreement). We defined agreement if at least 70% of experts voted ≥7. The level of evidence and grade or recommendation was assessed using the Oxford Centre for Evidence-based Medicine Levels of Evidence. The full text was circulated and reviewed by the panel. The consensus was coordinated by an expert methodologist. Results. A total of 20 recommendations were proposed. They include the validity of US and MRI regarding inflammation and damage detection, diagnosis, prediction (structural damage progression, flare, treatment response, etc.), monitoring and the use of US guided injections/biopsies. Conclusions. These recommendations will help clinicians use US and MRI in RA patients (AU)

Recomendaciones para el uso de la ecografía y la resonancia magnética en pacientes con espondiloartritis, incluyendo la artritis psoriásica, y en pacientes con artritis idiopática juvenil / Recommendations for the use of ultrasound and magnetic resonance in patients with spondyloarthritis, including psoriatic arthritis, and patients with juvenile idiopathic arthritis

Objetivo. Establecer recomendaciones, basadas en la evidencia, sobre el uso de la ecografía (US) y la resonancia magnética en pacientes con espondiloartritis, incluyendo la artritis psoriásica, y en la artritis idiopática juvenil. Métodos. Las recomendaciones se consensuaron mediante metodología basada en grupos nominales. Un grupo de expertos (15 reumatólogos y 3 radiólogos) definió el alcance, los usuarios, los apartados, las posibles recomendaciones y las revisiones sistemáticas a realizar (se utilizaron y actualizaron las revisiones de documentos de consenso de EULAR), y se asignaron tareas. Los expertos delimitaron los apartados y redactaron las recomendaciones. El nivel de evidencia y el grado de recomendación se establecieron utilizando el sistema del Centre for Evidence Based Medicine de Oxford, y el grado de acuerdo mediante Delphi a 2 rondas. Las recomendaciones se votaron según una escala de 1 (total desacuerdo) a 10 (total acuerdo), definiéndose el acuerdo como una puntuación≥7 por al menos el 70% de los participantes. El documento fue revisado por los expertos y el proyecto estuvo coordinado por un metodólogo experto. Resultados. Se emitieron 12 recomendaciones sobre la validez de la US y la resonancia magnética para la detección de actividad y daño estructural, capacidad diagnóstica, predictora (de progresión de daño estructural, brote de la enfermedad, respuesta al tratamiento, etc.), utilidad en la evaluación y monitorización del tratamiento, y uso de la US como guía (para infiltraciones, biopsias, etc.) en pacientes con espondiloartritis y artritis idiopática juvenil. Conclusiones. Se presentan unas recomendaciones útiles para el manejo de la US y la resonancia magnética por los clínicos en pacientes con espondiloartritis y artritis idiopática juvenil (AU)

Objective. To develop evidence-based recommendations on the use of ultrasound (US) and magnetic resonance imaging in patients with spondyloarthritis, including psoriatic arthritis, and juvenile idiopathic arthritis. Methods. Recommendations were generated following a nominal group technique. A panel of experts (15 rheumatologists and 3 radiologists) was established in the first panel meeting to define the scope and purpose of the consensus document, as well as chapters, potential recommendations and systematic literature reviews (we used and updated those from previous EULAR documents). A first draft of recommendations and text was generated. Then, an electronic Delphi process (2 rounds) was carried out. Recommendations were voted from 1 (total disagreement) to 10 (total agreement). We defined agreement if at least 70% of participants voted≥7. The level of evidence and grade or recommendation was assessed using the Oxford Centre for Evidence Based Medicine levels of evidence. The full text was circulated and reviewed by the panel. The consensus was coordinated by an expert methodologist. Results. A total of 12 recommendations were proposed for each disease. They include, along with explanations of the validity of US and magnetic resonance imaging regarding inflammation and damage detection, diagnosis, prediction (structural damage progression, flare, treatment response, etc.), monitoring and the use of US guided injections/biopsies. Conclusions. These recommendations will help clinicians use US and magnetic resonance imaging in patients with spondyloarthritis and juvenile idiopathic arthritis (AU)

Treatment with methotrexate and risk of relapses in patients with giant cell arteritis in clinical practice.

OBJECTIVES: To assess the incidence and the risk of relapses in giant cell arteritis (GCA) patients treated with and without methotrexate (MTX) in clinical practice. Other associated factors were also investigated. METHODS: An inception cohort of GCA was assembled in the out-patient clinic at Hospital Clínico San Carlos, including patients from the date of diagnosis (Jan-1991 until Sept-2013), and followed-up until lost of follow up or Sept-2014. MAIN OUTCOME: relapse defined as recurrence of symptoms or signs of GCA with high ESR and the need to increase glucocorticoids at least 10mg over the previous dose. The independent variable was exposure to MTX over time. Covariables: Sociodemographic, clinical, and treatment. Incidence rates of relapses (IR) per 100 patient-year with their 95% confidence intervals [CI] were estimated using survival techniques. MTX influence on relapses was analysed by Cox models. RESULTS: 168 patients were included (675 patient-year). 31% of patients had relapses (IR of 12 [9.6-14.9]), and the median number of relapses was 1[1-2]. 65% of the patients were on MTX, (mean dose: 10mg). In the bivariate analysis, the risk of relapses in patients with and without MTX did not achieve statistical signification (p=0.1). After adjusting in the multivariate analysis, exposure to MTX had 72% less risk of relapse compared to those without MTX (p<0.05). Other variables included in the final model were: visual alterations and malaise at clinical presentation of GCA. CONCLUSIONS: The use of MTX seems to decrease the risk of recurrences. We also found other factors influencing on relapses.

Recommendations for the use of ultrasound and magnetic resonance in patients with rheumatoid arthritis. / Recomendaciones para el uso de la ecografía y la resonancia magnética en pacientes con artritis reumatoide.

OBJECTIVE: To develop evidence-based recommendations on the use of ultrasound (US) and magnetic resonance imaging (MRI) in patients with rheumatoid arthritis (RA). METHODS: Recommendations were generated following a nominal group technique. A panel of experts, consisting of 15 rheumatologists and 3 radiologists, was established in the first panel meeting to define the scope and purpose of the consensus document, as well as chapters, potential recommendations and systematic literature reviews (we used and updated those from previous EULAR documents). A first draft of recommendations and text was generated. Then, an electronic Delphi process (2 rounds) was carried out. Recommendations were voted from 1 (total disagreement) to 10 (total agreement). We defined agreement if at least 70% of experts voted ≥7. The level of evidence and grade or recommendation was assessed using the Oxford Centre for Evidence-based Medicine Levels of Evidence. The full text was circulated and reviewed by the panel. The consensus was coordinated by an expert methodologist. RESULTS: A total of 20 recommendations were proposed. They include the validity of US and MRI regarding inflammation and damage detection, diagnosis, prediction (structural damage progression, flare, treatment response, etc.), monitoring and the use of US guided injections/biopsies. CONCLUSIONS: These recommendations will help clinicians use US and MRI in RA patients.

Recommendations for the Use of Ultrasound and Magnetic Resonance in Patients With Spondyloarthritis, Including Psoriatic Arthritis, and Patients With Juvenile Idiopathic Arthritis. / Recomendaciones para el uso de la ecografía y la resonancia magnética en pacientes con espondiloartritis, incluyendo la artritis psoriásica, y en pacientes con artritis idiopática juvenil.

OBJECTIVE: To develop evidence-based recommendations on the use of ultrasound (US) and magnetic resonance imaging in patients with spondyloarthritis, including psoriatic arthritis, and juvenile idiopathic arthritis. METHODS: Recommendations were generated following a nominal group technique. A panel of experts (15 rheumatologists and 3 radiologists) was established in the first panel meeting to define the scope and purpose of the consensus document, as well as chapters, potential recommendations and systematic literature reviews (we used and updated those from previous EULAR documents). A first draft of recommendations and text was generated. Then, an electronic Delphi process (2 rounds) was carried out. Recommendations were voted from 1 (total disagreement) to 10 (total agreement). We defined agreement if at least 70% of participants voted≥7. The level of evidence and grade or recommendation was assessed using the Oxford Centre for Evidence Based Medicine levels of evidence. The full text was circulated and reviewed by the panel. The consensus was coordinated by an expert methodologist. RESULTS: A total of 12 recommendations were proposed for each disease. They include, along with explanations of the validity of US and magnetic resonance imaging regarding inflammation and damage detection, diagnosis, prediction (structural damage progression, flare, treatment response, etc.), monitoring and the use of US guided injections/biopsies. CONCLUSIONS: These recommendations will help clinicians use US and magnetic resonance imaging in patients with spondyloarthritis and juvenile idiopathic arthritis.

Safety of disease-modifying antirheumatic drugs and biologic agents for rheumatoid arthritis patients in real-life conditions.

OBJECTIVE: The aim of this study was to describe the incidence rate (IR) of adverse drug reactions (ADRs) in daily clinical practice, related to disease-modifying antirheumatic drugs (DMARDs) and biologic agents (BA) in rheumatoid arthritis (RA) patients, and to analyze factors causing discontinuation due to ADRs. METHODS: This was a prospective observational study (October 2010 to October 2011). RA patients who were attended in our hospital taking DMARDs or BA during the study period were included. ADRs were injuries related to these drugs and registered with a software system in routine visits. ADRs could be mild (lowering dosage), moderate (drug discontinuation), or severe (hospital admission). The IR of ADR per 100 patient-years was estimated using survival techniques. Cox regression models (HR; 95% confidence interval) were used to explore factors associated with discontinuation due to ADRs. RESULTS: In total, 1202 patients were analyzed, with 158 ADRs (IR = 15.2). Of all ADRs, 80.4% required drug discontinuation (IR = 12.2). Age, less disease and therapy duration, taking corticoids, and combined therapy versus monotherapy (HR = 3; 95% CI: 2.0-4.4) were the factors independently associated to discontinuation due to ADRs. We did not find statistical differences between the different monotherapy regimens. Regarding combinations, Methotrexate + BA had the lowest risk of discontinuation compared to the rest (HR = 0.24; 95% CI: 0.09-0.6). CONCLUSIONS: We have estimated the incidence of ADRs related to DMARDs/BA in real-life conditions. We confirm the role of combined therapy in the development of discontinuations due to ADRs, except for BA + MTX, which did not show an increase of toxicity compared to monotherapy. This combination seems to be safer than others.

Automated radiofrequency-based US measurement of common carotid intima-media thickness in RA patients treated with synthetic vs synthetic and biologic DMARDs.

OBJECTIVE: To compare the carotid intima-media thickness (IMT) assessed with automated radiofrequency-based US in RA patients treated with synthetic vs synthetic and biologic DMARDs and controls. METHODS: Ninety-four RA patients and 94 sex- and age-matched controls were prospectively recruited at seven centres. Cardiovascular (CV) risk factors and co-morbidities, RA characteristics and therapy were recorded. Common carotid artery (CCA)-IMT was assessed in RA patients and controls with automated radiofrequency-based US by the same investigator at each centre. RESULTS: Forty-five (47.9%) RA patients had been treated with synthetic DMARDs and 49 (52.1%) with synthetic and biologic DMARDs. There were no significant differences between the RA patients and controls in demographics, CV co-morbidities and CV disease. There were significantly more smokers among RA patients treated with synthetic and biologic DMARDs (P = 0.036). Disease duration and duration of CS and synthetic DMARD therapy was significantly longer in RA patients treated with synthetic and biologic DMARDs (P < 0.0005). The mean CCA-IMT was significantly greater in RA patients treated only with synthetic DMARDs than in controls [591.4 (98.6) vs 562.1 (85.8); P = 0.035] and in RA patients treated with synthetic and biologic DMARDs [591.4 (98.6) vs 558.8 (95.3); P = 0.040). There was no significant difference between the mean CCA-IMT in RA patients treated with synthetic and biologic DMARDs and controls (P = 0.997). CONCLUSION: Our results suggest that radiofrequency-based measurement of CCA-IMT can discriminate between RA patients treated with synthetic DMARDs vs RA patients treated with synthetic and biologic DMARDs.

Prognostic factors for long-term work disability due to musculoskeletal disorders.

The objective of this study is to identify risk factors for permanent work disability (PWD) related to musculoskeletal disorders (MSDs). This is a secondary data analysis of a randomized controlled intervention study in Temporary Work Disability (TWD) due to MSDs. The association of PWD (claim submission and status recognition) with baseline clinical, sociodemographic, work-related administrative and occupational factors was analyzed by Cox proportional hazards models. Of 3,311 patients with TWD, 47 submitted a PWD claim, of whom 32 achieved PWD status. The main alleged causes of the PWD were back pain, sciatica, and inflammatory diseases. The following factors were independently associated with an increased probability of PWD claim submission: age (odds ratio (OR) 5.1), being woman (OR 2.1), self-employment (OR 3.4), unemployment (OR 13.8), previous musculoskeletal surgery (OR 16), repeated TWD (OR 3.4), sitting (OR 2.8), and raising arms frequently (OR 3.1). Patients with inflammatory disease were more likely to file PWD claims (OR 10.4) while tendonitis was associated with lower probability (OR 0.3). The sociodemographic factors that better predicted PWD status recognition were age (OR 5.7), low educational level (OR 4.2), previous musculoskeletal surgery (OR 14.9), unemployment (OR 17.6), sitting (OR 2.6), and raising arms frequently (OR 2.7). Inflammatory diseases were the diagnoses associated with a higher rate of PWD status recognition (OR 6.1). Inflammatory diseases have a high chronic disability potential in active workers. Sociodemographic, work-related, occupational factors, and other clinical factors, some of which are modifiable, may explain the development of long-term work disability related to MSDs.

Multi-examiner reliability of automated radio frequency-based ultrasound measurements of common carotid intima-media thickness in rheumatoid arthritis.

OBJECTIVES: To assess the reliability of the automated radio frequency (RF)-based US measurement of carotid intima-media thickness (IMT) performed by rheumatologists and to evaluate the variability between this method and the conventional B-mode US measurement of carotid IMT in RA patients. METHODS: Twelve rheumatologists measured in two blinded rounds the IMT of both common carotid arteries (CCAs) of seven RA patients with an automated RF-based method. At each round, a cardiologist measured both CCA-IMTs of the patients using an automated B-mode method. Inter-observer reliability for RF-based IMT measurements was evaluated by the intra-class correlation coefficient (ICC). Intra-observer reliability for RF-based IMT measurements was assessed using the root mean square coefficient of variation (RMS-CV), Bland-Altman method and ICC. Agreement between the two US methods was evaluated by the Bland-Altman method, ICC and RMS-CV. RESULTS: Inter-observer ICCs for the RF-based CCA-IMT measurements were 0.85 (95% CI 0.69, 0.94) for the first round, and 0.77 (95% CI 0.55, 0.91) for the second round. RMS-CVs for the RF-based CCA-IMT measurements varied from 5.6 to 11.7%. The mean intra-observer ICC for the RF-based CCA-IMT measurements was 0.61 (95% CI 0.46, 0.71). In the Bland-Altman analysis for agreement between RF-based and B-mode CCA-IMT measurements, the mean difference varied from -0.6 to -19.7 µm. Inter-method ICCs varied from 0.57 to 0.83 for 11 rheumatologists. Inter-method RMS-CVs varied from 11.3 to 13.7%. CONCLUSIONS: Our results suggest that automated RF-based CCA-IMT measurement performed by rheumatologists can be a reliable method for assessing cardiovascular risk in RA patients.

Variability in the use of orthopedic surgery in patients with rheumatoid arthritis in Spain.

OBJECTIVE: To analyze sociodemographic and clinic-associated factors of patients with rheumatoid arthritis (RA) undergoing any orthopedic surgery (AOS) and total joint replacement (TJR) in Spain. METHODS: A retrospective medical record review was performed in a probabilistic sample of 1379 RA patients from 46 centers distributed in 16 of 19 regions in Spain. Sociodemographic and clinical features, use of drugs, and arthritis-related joint surgeries were recorded following a standardized protocol. Gross domestic product (GDP) data were obtained from the National Statistical Index. RESULTS: Of 1379 patients, a total of 358 (26%) underwent one or more joint surgeries, and 194 (14%) had a TJR. The median time to first orthopedic procedure was 12.5 years from presentation of RA and the estimated rate was 5.6 surgeries per 100 person-years. The rate of AOS was increased in women, patients with RA with extraarticular complications, with longterm RA (> 10 yrs), with functional grade III-IV, and with persistent inflammatory disease. The risk factors for undergoing a TJR were longterm RA, functional grade III-IV, and extraarticular complications. Patients from regions with higher GDP per capita were more likely to undergo a procedure. CONCLUSION: Clinical variables reflecting disease activity and severity are predictors of orthopedic surgery, but geographic and socioeconomic variables were also independently associated with the rate of orthopedic surgery.

Estudio sobre el manejo de la artritis reumatoide en españa (emAR) (I). Características de los centros participantes / Study of the management of rheumatoid arthritis in Spain (emAR) (I). Characteristics of participating centers

Fundamento: El Estudio sobre el manejo de la artritis reumatoide (AR) en España ha permitido analizar las características de los médicos, los servicios clínicos y los hospitales en los que se atiende a pacientes con AR. Material y método: Revisión de 1.379 historias clínicas de pacientes con AR seleccionadas de forma aleatoria y atendidos en 48 servicios de atención especializada de 16 comunidades autónomas. Se analizaron las características generales de los médicos, servicios clínicos y hospitales participantes. Resultados: La tasa de participación fue de 46/78 hospitales contactados (59 por ciento). Existía un médico responsable en el 87 por ciento de los pacientes (en 5 hospitales este porcentaje no superó el 40 por ciento). La mitad de los pacientes eran atendidos por médicos entre 41 y 50 años y en un 75 por ciento eran varones. El 91 por ciento de los médicos eran reumatólogos. En el 86,5 por ciento de los casos todas las visitas fueron realizadas en el hospital. El número de médicos por servicio varió entre menos de tres (37 por ciento), entre tres y seis (41 por ciento) y más de seis (22 por ciento). La mediana de habitantes por reumatólogo fue de 86.250. El 20 por ciento de los servicios disponía de consulta monográfica de AR, y sólo el 26 por ciento de consulta de enfermería. En el 54 por ciento de los servicios, la monitorización de los fármacos se realizaba conjuntamente con atención primaria. Ninguna de estas características se relacionó con la dotación Estudio sobre el Manejo de la Artritis Reumatoide en España (emAR) (I). Características de los centros participantes de recursos humanos ni en cifras absolutas ni ajustando en función del área atendida. Conclusiones: Los recursos personales y organizativos disponibles para la atención de pacientes con AR son muy variables entre centros sanitarios de la red pública (AU)

Estudio descriptivo de la cirugía ortopédica realizada a los pacientes atendidos en un servicio de reumatología de un hospital terciario en un período de 5 años / A descriptive study of orthopedic surgery performed over a five-year period in patients seen in a Rheumatology Department of a tertiary hospital

Objetivo: Describir la cirugía ortopédica realizada a los pacientes atendidos en una consulta de reumatología durante el período 1993-1997. Métodos: Se contabilizaron todas las intervenciones quirúrgicas realizadas en ese período. De cada paciente se recogieron las siguientes variables: datos demográficos, diagnóstico reumatológico según el CIE-9MC, tipo de cirugía y región anatómica de la cirugía. Se agruparon las cirugías según el diagnóstico reumatológico en enfermedad inflamatoria y no inflamatoria. Resultados: Se realizaron 557 intervenciones a 429 pacientes. Más del 70 por ciento eran mujeres y con una edad media en el momento de la cirugía correspondiente a la séptima década. El 64,2 por ciento de la cirugía se realizó al grupo de enfermedad no inflamatoria, y la artroplastia fue la intervención más frecuente en los dos grupos. La artrosis y la artritis reumatoide fueron las enfermedades más comunes de cada grupo; en ambos la rodilla fue la articulación más intervenida. En el grupo AR, las intervenciones sobre la mano (p = 0,0001) y el pie (p = 0,003) fueron significativamente más frecuentes que en la artrosis; asimismo, en cuanto al procedimiento quirúrgico la sinovectomía fue significativamente más frecuente en la artritis reumatoide (p = 0,003). Conclusiones: La cirugía ortopédica que más se realizó en esta serie fue la artroplastia. La cirugía funcional (sinovectomías, artrodesis, etc.), aunque más frecuente en la artritis reumatoide constituye un porcentaje bajo del total. La rodilla es la articulación más operada en la artritis reumatoide y la artrosis; la mano y el pie son regiones significativamente más intervenidas en esta enfermedad. (AU)