Real-world Effectiveness and Safety of JAK Inhibitors in Rheumatoid Arthritis: A Single-centre Study / Efectividad y seguridad en el mundo real de los inhibidores de JAK en la artritis reumatoide: Estudio unicéntrico

Background/objective: To assess the effectiveness and safety of Baricitinib and Tofacitinib in rheumatoid arthritis (RA) patients in “real world” conditions. Methods: A single centre retrospective study was performed including RA patients who had initiated treatment with Baricitinib or Tofacitinib from September-2017 to January-2020. Demographic, clinical, laboratory, efficacy and safety variables were collected from baseline and at months 1, 3, 6, 12, 18 and 24. Effectiveness was evaluated by changes from the baseline in DAS28, SDAI, HAQ and acute phase reactants. Safety analysis included adverse events due to any cause, including infection or intolerance. Infection was considered severe if it implied hospitalization. Statistical analysis consisted in Bayesian mixed ordinal regression models including the monotonic effect of each visit and Kaplan–Meier survival curves. Results: Overall, 98 patients were included. A significant reduction of disease activity scores was noted in both groups. No difference between either treatment was detected in terms of effectiveness even in first line, after bDMARD failure, in monotherapy nor combined therapy. A total of 54 adverse events were recorded of which 18 were considered relevant. The incidence of infection, including Herpes Zoster, was similar in both groups. No patients in either group suffered any tuberculosis, thromboembolic event, malignancy, death or cardiovascular adverse events. Survival analysis did not show any difference between groups. Conclusion: Baricitinib and Tofacitinib are both comparable in terms of effectiveness and safety in real world conditions.(AU)

Antecedentes/objetivo: Evaluar la efectividad y seguridad de baricitinib y tofacitinib en los pacientes con artritis reumatoide (AR) en condiciones del «mundo real». Métodos: Se realizó un estudio retrospectivo unicéntrico que incluyó a los pacientes de AR que habían iniciado tratamiento con baricitinib o tofacitinib de septiembre de 2017 a enero de 2020. Se recopilaron las variables demográficas, clínicas, de laboratorio, de eficacia y seguridad a nivel basal, y transcurridos uno, 3, 6, 12, 18 y 24 meses. La efectividad se evaluó mediante los cambios desde el punto basal en cuanto a DAS28, SDAI, HAQ y los reactantes de fase aguda. El análisis de seguridad incluyó los episodios adversos debido a cualquier causa, incluyendo infección o intolerancia. Se consideró infección grave cuando se produjo hospitalización. El análisis estadístico consistió en modelos mixtos de regresión ordinaria de Bayes incluyendo el efecto monotónico de cada visita y las curvas de supervivencia de Kaplan-Meier. Resultados: En total se incluyeron 98 pacientes. Se observó una reducción significativa de la actividad de la enfermedad en ambos grupos. No se detectó diferencia alguna entre ninguno de los tratamientos en términos de efectividad incluso en primera línea, tras el fallo de bDMARD, en monoterapia ni en terapia combinada. Se registró un total de 54 episodios adversos, de los cuales se consideraron relevantes 18. La incidencia de la infección, incluyendo herpes zoster, fue similar en ambos grupos. Ningún paciente de cualquiera de los grupos padeció episodios adversos tales como tuberculosis, episodio tromboembólico, malignidad, muerte ni episodios adversos de tipo cardiovascular. El análisis de supervivencia no reflejó diferencia alguna entre los grupos. Conclusión: Baricitinib y tofacitinib son comparables en términos de efectividad y seguridad en condiciones del mundo real.(AU)

Cardiovascular risk assessment with carotid ultrasound in rheumatoid arthritis

Background/Objective: To assess the Cardiovascular Risk (CV) in Rheumatoid Arthritis (RA) patients using carotid ultrasound additionally to the traditional CV risk factors.MethodsA cross-sectional case control study was performed including RA patients and matched controls. This study was performed from July-2019 to January-2020. Population over 75 years old, established CV disease and/or chronic kidney disease (from III Stage) were excluded. Statistical analysis included a multivariate variance analysis (Manova) and a negative binomial regression adjusted by confounding factors.ResultsOverall, a total of 200 cases and 111 controls were included in the study. Demographical and clinical variables were comparable between groups. A relationship between age, BMI and high blood pressure was detected in both groups. RA patients showed higher intima-media thickness and higher plaque account compared to controls and it was related to the disease duration and DAS28 score.ConclusionRA leads to a higher intima-media thickness, and this is related to the disease duration and DAS28 score. These findings support that RA acts as an independent cardiovascular risk factor. (AU)

Objetivo: Evaluar el riesgo cardiovascular (RCV) en pacientes con artritis reumatoide (AR) mediante el empleo de la ecografía de carótidas en adición a los factores de riesgo cardiovascular clásicos.MétodosSe realizó un estudio de casos y controles transversal incluyendo pacientes con AR y controles voluntarios sin historia de eventos cardiovasculares. El estudio se llevó a cabo entre julio de 2019 y enero de 2020. Se excluyeron individuos con edad por encima de los 75 años, enfermedad cardiovascular establecida y/o enfermedad renal crónica.ResultadosEn total, se incluyeron 200 pacientes con AR y 111 controles. Las variables demográficas y clínicas fueron comparables entre los grupos de estudio. Se halló correlación entre la edad, el IMC y la presencia de hipertensión arterial en ambos grupos. Los pacientes con AR evidenciaron un mayor grosor íntima-media y una mayor presencia de placas en el estudio de ecografía carotídea respecto a los controles y además demostró guardar relación con una mayor duración de la enfermedad.ConclusionesLa AR conlleva el desarrollo de un mayor grosor íntima-media y ello correlaciona con la duración y la actividad de la enfermedad, lo cual apoya que la AR actúa como un factor de riesgo cardiovascular independiente. (AU)

Real-world Effectiveness and Safety of JAK Inhibitors in Rheumatoid Arthritis: A Single-centre Study.

BACKGROUND/OBJECTIVE: To assess the effectiveness and safety of Baricitinib and Tofacitinib in rheumatoid arthritis (RA) patients in "real world" conditions. METHODS: A single centre retrospective study was performed including RA patients who had initiated treatment with Baricitinib or Tofacitinib from September-2017 to January-2020. Demographic, clinical, laboratory, efficacy and safety variables were collected from baseline and at months 1, 3, 6, 12, 18 and 24. Effectiveness was evaluated by changes from the baseline in DAS28, SDAI, HAQ and acute phase reactants. Safety analysis included adverse events due to any cause, including infection or intolerance. Infection was considered severe if it implied hospitalization. Statistical analysis consisted in Bayesian mixed ordinal regression models including the monotonic effect of each visit and Kaplan-Meier survival curves. RESULTS: Overall, 98 patients were included. A significant reduction of disease activity scores was noted in both groups. No difference between either treatment was detected in terms of effectiveness even in first line, after bDMARD failure, in monotherapy nor combined therapy. A total of 54 adverse events were recorded of which 18 were considered relevant. The incidence of infection, including Herpes Zoster, was similar in both groups. No patients in either group suffered any tuberculosis, thromboembolic event, malignancy, death or cardiovascular adverse events. Survival analysis did not show any difference between groups. CONCLUSION: Baricitinib and Tofacitinib are both comparable in terms of effectiveness and safety in real world conditions.

Utility of cytokines CXCL4, CXCL8 and GDF15 as biomarkers in systemic sclerosis

Background and objectives: Systemic sclerosis (SSc) is an autoinmune disease that can affect several organs and its mortality is fundamentally related to its pulmonary involvement. There are some cytokines with high serum levels of patients with SSc. Our goal is to determine the role of CXCL4, CXCL8 and GDF15 in the physiopathology of SSc and whether they can be considered organic damage biomarkers.Patients and methodsObservational case–control study of SSc patients (ACR/EULAR 2013 criteria). Demographic, clinical, analytical, activity, severity, health perception, and disability variables were collected. Moreover, Videocapillaroscopy, Echocardiography and Respiratory Function Test were made. Serum levels of CXCL4, CXCL8 and GDF15 were measured both in SSc patients and in healthy controls.ResultsA total of 42 patients were included (95.4% women), with an average age of 59.2 years and a median of 4 years from diagnosis. We also included 42 healthy controls. We found significantly higher levels of GDF15 in SSc patients than in controls (p<0.001), but no higher CXCL4 or CXCL8 levels. GDF15 was associated with Diffuse SSc, pulmonary arterial hypertension, interstitial lung disease, less forced vital capacity, high titles of antiScl70, disease activity, and dilated loops in capillaroscopy. CXCL4 levels were associated to a higher Rodnan punctuation, while CXCL8 was associated to C4 fraction consumption and tortuosities in capillaroscopy. (AU)

Antecedentes y objetivos: La esclerosis sistémica (ES) es una enfermedad autoinmunitaria que afecta a diferentes órganos y cuya mortalidad se relaciona fundamentalmente con su afectación pulmonar. Los pacientes con ES presentan niveles séricos elevados de algunas citocinas. Nuestro objetivo es determinar el papel de CXCL4, CXCL8 y GDF15 en la fisiopatología de la ES, y si pueden considerarse biomarcadores de daño orgánico.Pacientes y métodosEstudio observacional de casos-controles, con pacientes afectados de ES (criterios ACR/EULAR 2013) y controles sanos. Se determinaron los niveles séricos de CXCL4, CXCL8 y GDF15 en ambos grupos, y se registraron variables demográficas, clínicas, analíticas, de actividad, gravedad, percepción de salud y discapacidad de pacientes con ES, a quienes, además, se les realizó videocapilaroscopia, ecocardiograma y espirometría.ResultadosSe incluyeron 42 pacientes (95,4% mujeres), con una edad media de 59,2 años y una mediana de 4 años desde el diagnóstico, con 42 controles sanos. Se hallaron niveles significativamente mayores de GDF15 en pacientes con ES que en controles (p<0,001), pero no de CXCL4 ni CXCL8. GDF15 se asoció a ES difusa, hipertensión pulmonar, enfermedad pulmonar intersticial, menor capacidad vital forzada, títulos altos de anti-Scl70, actividad de ES y dilataciones capilares. Asimismo, los niveles de CXCL4 se asociaron a mayor afectación cutánea (Rodnan), mientras que CXCL8 se asoció a consumo de la fracción C4 del complemento y tortuosidades en la capilaroscopia. (AU)

Cardiovascular risk assessment with carotid ultrasound in rheumatoid arthritis.

BACKGROUND/OBJECTIVE: To assess the Cardiovascular Risk (CV) in Rheumatoid Arthritis (RA) patients using carotid ultrasound additionally to the traditional CV risk factors. METHODS: A cross-sectional case control study was performed including RA patients and matched controls. This study was performed from July-2019 to January-2020. Population over 75 years old, established CV disease and/or chronic kidney disease (from III Stage) were excluded. Statistical analysis included a multivariate variance analysis (Manova) and a negative binomial regression adjusted by confounding factors. RESULTS: Overall, a total of 200 cases and 111 controls were included in the study. Demographical and clinical variables were comparable between groups. A relationship between age, BMI and high blood pressure was detected in both groups. RA patients showed higher intima-media thickness and higher plaque account compared to controls and it was related to the disease duration and DAS28 score. CONCLUSION: RA leads to a higher intima-media thickness, and this is related to the disease duration and DAS28 score. These findings support that RA acts as an independent cardiovascular risk factor.

CT-Guided Needle Biopsy in Vertebral Osteomyelitis: Study of Factors That Could Influence in Culture Yield.

OBJECTIVE: The aim of this study was to analyze which are the main factors that could influence the result of a CT guided biopsy in vertebral osteomyelitis (VO) patients. METHODS: A single center retrospective observational study was performed including adult patients who had been diagnosed with VO and undergone CT guided needle biopsy from January 2010 to January 2020. Demographical features, concurrent diseases, laboratory findings, microbiological diagnosis, radiological data, medical complications, antibiotic exposure were compiled. Multivariate analysis was performed with a logistic regression comparing the patients depending on the culture result. RESULTS: Seventy-seven patients were included in the study. Baseline characteristics were comparable between groups. Sample culture was positive in 43 cases (56%). Microorganism isolated were gram+(72%), gram-(14%), mycobacteria (7%) and fungi (7%). Delay in the procedure, antibiotic exposure and blood culture positivity were also similar among both groups. The biopsy results were not influenced by the CRP value, the presence of fever nor antibiotic exposure. The longer duration of back pain was associated to a lower probability of a positive culture. CONCLUSIONS: In conclusion, our study displays an acceptable reliability of CT guided needle biopsy in VO patients, even in cases under antibiotic treatment. The presence of fever or CRP values did not predict a positive culture. Delay in diagnosis could impact negatively on culture yield.

Utility of cytokines CXCL4, CXCL8 and GDF15 as biomarkers in systemic sclerosis.

BACKGROUND AND OBJECTIVES: Systemic sclerosis (SSc) is an autoinmune disease that can affect several organs and its mortality is fundamentally related to its pulmonary involvement. There are some cytokines with high serum levels of patients with SSc. Our goal is to determine the role of CXCL4, CXCL8 and GDF15 in the physiopathology of SSc and whether they can be considered organic damage biomarkers. PATIENTS AND METHODS: Observational case-control study of SSc patients (ACR/EULAR 2013 criteria). Demographic, clinical, analytical, activity, severity, health perception, and disability variables were collected. Moreover, Videocapillaroscopy, Echocardiography and Respiratory Function Test were made. Serum levels of CXCL4, CXCL8 and GDF15 were measured both in SSc patients and in healthy controls. RESULTS: A total of 42 patients were included (95.4% women), with an average age of 59.2 years and a median of 4 years from diagnosis. We also included 42 healthy controls. We found significantly higher levels of GDF15 in SSc patients than in controls (p<0.001), but no higher CXCL4 or CXCL8 levels. GDF15 was associated with Diffuse SSc, pulmonary arterial hypertension, interstitial lung disease, less forced vital capacity, high titles of antiScl70, disease activity, and dilated loops in capillaroscopy. CXCL4 levels were associated to a higher Rodnan punctuation, while CXCL8 was associated to C4 fraction consumption and tortuosities in capillaroscopy. CONCLUSIONS: GDF15 high levels were associated with diffuse SSc, lung impairment, disease activity and changes in capillaroscopy. Moreover, CXCL4 was only associated with skin impairment, while CXCL8 was not related to organic damage.

CT-Guided Needle Biopsy in Vertebral Osteomyelitis: Study of Factors That Could Influence in Culture Yield / Punción asistida por TC en pacientes con osteomielitis vertebral: análisis de los factores que condicionan su rentabilidad

Objective: The aim of this study was to analyze which are the main factors that could influence the result of a CT guided biopsy in vertebral osteomyelitis (VO) patients. Methods: A single center retrospective observational study was performed including adult patients who had been diagnosed with VO and undergone CT guided needle biopsy from January 2010 to January 2020. Demographical features, concurrent diseases, laboratory findings, microbiological diagnosis, radiological data, medical complications, antibiotic exposure were compiled. Multivariate analysis was performed with a logistic regression comparing the patients depending on the culture result. Results: Seventy-seven patients were included in the study. Baseline characteristics were comparable between groups. Sample culture was positive in 43 cases (56%). Microorganism isolated were gram+(72%), gram−(14%), mycobacteria (7%) and fungi (7%). Delay in the procedure, antibiotic exposure and blood culture positivity were also similar among both groups. The biopsy results were not influenced by the CRP value, the presence of fever nor antibiotic exposure. The longer duration of back pain was associated to a lower probability of a positive culture. Conclusions: In conclusion, our study displays an acceptable reliability of CT guided needle biopsy in VO patients, even in cases under antibiotic treatment. The presence of fever or CRP values did not predict a positive culture. Delay in diagnosis could impact negatively on culture yield.(AU)

Objetivo: El propósito del presente estudio es analizar qué factores pueden influir en el resultado del cultivo de las muestras obtenidas por punción guiada por TC en pacientes con osteomielitis vertebral. Métodos: Se realizó un estudio en un único centro, retrospectivo y observacional en pacientes diagnosticados de osteomielitis vertebral, que fueron subsidiarios de punción-biopsia entre enero de 2010 y enero de 2020. Se recogieron para su análisis, variables demográficas, comorbilidades, resultados de laboratorio, radiología, el tratamiento previo con antibióticos y la demora previa a la realización de la técnica. Se realizó un análisis multivariante mediante regresión logística. Resultados: Se incluyó a un total de 77 pacientes que fueron sometidos a la técnica. Sus características basales fueron similares. El cultivo fue positivo en 43 casos (56%). Los microorganismos aislados fueron gram + (72%), gram – (14%), micobacterias (7%) y hongos (7%). El retraso en la ejecución de la técnica y el tratamiento previo con antibióticos fue similar en ambos grupos. Ni el valor de PCR, la presencia de fiebre ni la antibioterapia tuvieron influencia en el resultado del cultivo. Se observó que una mayor duración del dolor lumbar se relacionó con una menor probabilidad de obtener un resultado positivo en el cultivo. Conclusiones: Incluso bajo exposición antibiótica, la punción asistida por TC mostró una rentabilidad aceptable. La presencia de fiebre o valores elevados de PCR no fueron predictivos de positividad del cultivo. El retraso diagnóstico sí podría impactar negativamente en la rentabilidad diagnóstica del cultivo procedente de la biopsia.(AU)

Vertebral osteomyelitis: Clinical, microbiological and radiological characteristics of 116 patients / Osteomielitis vertebral: características clínicas, microbiológicas y radiológicas de 116 pacientes

INTRODUCTION/OBJECTIVES: To describe the clinical, radiological and microbiological characteristics of vertebral osteomyelitis patients, analysing the factors that played a role on their outcome. PATIENTS AND METHODS: Single-centre retrospective observational study including patients diagnosed with vertebral osteomyelitis, based on the combination of clinical presentation with either a definitive bacteriological diagnosis and/or imaging studies. RESULTS: 116 adult patients were included with a mean age of 62.75 (14.98) years. Males predominated (68.10%). Eighteen patients (15.51%) were immunosuppressed. The most frequent symptom was back pain (99.14%) followed by fever, which was detected in 45 patients (38.79%). Puncture-aspiration or biopsy was performed in 84 patients (72.10%) and its culture was positive in 48 samples (57.14%). Gram positive species predominated (73.86%) on cultures, followed by Gram negative (12.5%), mycobacteria (10.23%) and fungi (3.41%). No microorganism was identified in 28 patients (24.14%). On imaging, most of the patients (92.24%) had paravertebral or epidural abscess. 63 cases (54.31%) showed vertebral destruction and 39 (33.62%) cord compression. Twenty-two patients (18.97%) required further surgical procedures and 13 (11.21%) died. CONCLUSIONS: The average patient is middle aged (often male) with a history of subacute back pain, sometimes presenting fever and/or neurological damage on diagnosis. Acute phase reactants are frequently raised. Diabetes mellitus, endocarditis and immunosuppressed patients may have the worst chance of a good outcome, therefore these patients should be more carefully managed (always try to obtain an imaging-guided biopsy, correct antibiotic treatment, and a functional and clinical follow-up)

INTRODUCCIÓN/OBJETIVOS: Describir las características clínicas, radiológicas y microbiológicas de pacientes con osteomielitis vertebral en nuestro centro, analizando qué variables tuvieron influencia pronóstica. MATERIAL Y MÉTODOS: Se llevó a cabo un estudio observacional, unicéntrico y retrospectivo incluyendo pacientes adultos diagnosticados de osteomielitis vertebral sobre la base de la combinación de las manifestaciones clínicas con un diagnóstico microbiológico y/o radiológico compatible. RESULTADOS: Se incluyeron un total de 116 pacientes con una media de edad de 62,75 (14,98) años, predominando el género masculino (68,10%). Dieciocho de ellos (15,51%) estaban inmunosuprimidos. El síntoma más frecuente fue el dolor lumbar (99,14%) seguido de la fiebre, detectada en 45 pacientes (38,79%). Se realizó punción-biopsia en 84 pacientes (72,10%) con positividad en el cultivo en 48 muestras (57,14%) donde predominó el crecimiento de Gram positivos (73,86%) seguido de Gram negativos (12,5%), micobacterias (10,23%) y hongos (3,41%). En 28 pacientes (24,14%) no se pudo identificar el agente causal. En el estudio de resonancia magnética, la mayoría de los pacientes tenían abscesificación paravertebral o epidural (92,24%); 63 pacientes (54,31%) tenían hallazgos compatibles con destrucción vertebral y 39 (33,62%), compresión medular. En 22 casos (18,97%) se requirió un abordaje quirúrgico posterior. Trece pacientes (11,21%) fallecieron a causa de la infección o de sus complicaciones. CONCLUSIONES: El paciente promedio es un varón de edad media, con historia de dolor lumbar de curso subagudo e insidioso, con presencia inconstante de fiebre, presente en menos de la mitad de los casos. Con relativa frecuencia se ha detectado una exploración neurológica patológica en la presentación clínica. Los reactantes de fase aguda estaban elevados en la mayoría de los pacientes. Los casos en los que exista comorbilidad (sobre todo diabetes mellitus o inmunosupresión), así como la concomitancia con endocarditis, debe de implicar un manejo más cauto

Vertebral osteomyelitis: Clinical, microbiological and radiological characteristics of 116 patients.

INTRODUCTION/OBJECTIVES: To describe the clinical, radiological and microbiological characteristics of vertebral osteomyelitis patients, analysing the factors that played a role on their outcome. PATIENTS AND METHODS: Single-centre retrospective observational study including patients diagnosed with vertebral osteomyelitis, based on the combination of clinical presentation with either a definitive bacteriological diagnosis and/or imaging studies. RESULTS: 116 adult patients were included with a mean age of 62.75 (14.98) years. Males predominated (68.10%). Eighteen patients (15.51%) were immunosuppressed. The most frequent symptom was back pain (99.14%) followed by fever, which was detected in 45 patients (38.79%). Puncture-aspiration or biopsy was performed in 84 patients (72.10%) and its culture was positive in 48 samples (57.14%). Gram positive species predominated (73.86%) on cultures, followed by Gram negative (12.5%), mycobacteria (10.23%) and fungi (3.41%). No microorganism was identified in 28 patients (24.14%). On imaging, most of the patients (92.24%) had paravertebral or epidural abscess. 63 cases (54.31%) showed vertebral destruction and 39 (33.62%) cord compression. Twenty-two patients (18.97%) required further surgical procedures and 13 (11.21%) died. CONCLUSIONS: The average patient is middle aged (often male) with a history of subacute back pain, sometimes presenting fever and/or neurological damage on diagnosis. Acute phase reactants are frequently raised. Diabetes mellitus, endocarditis and immunosuppressed patients may have the worst chance of a good outcome, therefore these patients should be more carefully managed (always try to obtain an imaging-guided biopsy, correct antibiotic treatment, and a functional and clinical follow-up).

The role of 18F-FDG PET/CT in early infectious discitis: a case report after a negative MRI.

We present the case of a 70 years old woman with infectious discitis which was detected using Fluorine fluodeoxiglucose positron emission tomography/computed tomography (18F-FDG PET/CT), after a negative magnetic resonance imaging. A Streptococuss gallolyticus (bovis gender bacteria) grow on culture. In addition 18F-FDG PET also demonstrated infectious endocarditis which was confirmed by transesophageal echocardiography and a colonic neoplasm. Here we have highlighted the potential role of 18F-FDG PET/CT study in patients with a clinical history suggestive of infectious discitis with a negative or indifferent magnetic resonance imaging.