Can we predict the risk factors for switching due to ineffectiveness in the first year of therapy with bDMARD in patients with rheumatoid arthritis?

INTRODUCTION: Biological disease-modifying antirheumatic drugs (bDMARD) have improved the clinical course and quality of life of patients with rheumatoid arthritis (RA). However, some patients failed to respond or have an insufficient response to bDMARD early in the course of the treatment. OBJECTIVES: To determine the percentage of RA patients who need to switch due to ineffectiveness in the first year of treatment and to identify specific baseline features as possible predictors of switch due to ineffectiveness in the first year of treatment. MATERIALS AND METHODS: An observational retrospective study was conducted with patients with RA that started their first bDMARD. Demographic data, disease characteristics, disease activity data scores, laboratory parameters and treatment at baseline were collected. The proportion of patients who failed to respond and who switched to another bDMARD in the first year of treatment was calculated. RESULTS: A total of 437 (364 females, 83.3%) patients with RA were included. The majority of these patients started an anti-TNF-α agent (n=315, 72.1%). Forty-eight (11.0%) patients failed to respond to the bDMARD in the first year of treatment. There were significantly more current or former smokers (p=0.030), with a history of depression (p=0.003) and positive for RF at baseline (p=0.014) in the switch group. In the multivariate analysis, anti-TNF-α agents use (OR 8.3, 95% CI 2.4-28.8, p=0.001), tobacco exposure (OR 2.3, 95% CI 1.1-4.8, p=0.02) and history of depression (OR 3.1, 95% CI 1.3-7.7) seem to predict the need to switch in the first year of treatment due to ineffectiveness. DISCUSSION AND CONCLUSION: In our study, tobacco exposure and depression appear to be modifiable risk factors associated with early switching due to ineffectiveness. Addressing these factors in daily clinical practice is crucial to enhance the overall response to therapy and improve the well-being of patients.

Efficacy of disease-modifying antirheumatic drugs in primary Sjögren's syndrome-related interstitial lung disease.

OBJECTIVES: To evaluate the treatment modalities and their effects in primary Sjögren's syndrome (pSS) patients with interstitial lung disease (ILD). METHODS: In this chart review study, patients diagnosed with pSS-related ILD (pSS-ILD) between January 2004 and August 2022 were screened. Glucocorticoid use and administered disease-modifying antirheumatic drugs (DMARDs) were determined. The difference between forced vital capacity (FVC) and diffusion capacity of the lungs for carbon monoxide (DLCO) before and after treatment was evaluated. RESULTS: ILD was present in 44 of 609 patients (7.2%) diagnosed with pSS. In 27 patients included in the study, steroid usage was 81.5%. There was a statistically insignificant increase in FVC% (from 80.20±22.1 to 81.6±23.0) and a decrease in DLCO% (53.7±15.3-52.2±19.3) with DMARD treatment (p=0.434 and p=0.652, respectively). There was no significant difference between the treatment groups (azathioprine [AZA], mycophenolate mofetil [MMF], and rituximab [RTX]) in terms of the change in FVC% and DLCO% compared with baseline levels. The effect of treatment on FVC and DLCO was similar in UIP and NSIP patterns. CONCLUSIONS: AZA, MMF, and RTX have similar effects on pulmonary functions in pSS-ILD and provide disease stabilization.

[Impact of systemic therapies on SARS-CoV-2 antibody seroprevalence in patients with immune-mediated diseases]. / Impacto de las terapias sistémicas en la seroprevalencia de anticuerpos contra el SARS-CoV-2 en pacientes con enfermedades inmunomediadas.

OBJECTIVE: To determine the seroprevalence of SARS-CoV-2 in patients with immune-mediated inflammatory diseases (IMID) treated with biologic (bDMARDs) or synthetic targeted disease-modifying antirheumatic drugs (tsDMARDs). METHODS: An observational, descriptive, prospective and cross-sectional study of analytical prevalence analysis was conducted in patients with IMID with bDMARDs or tsDMARDs. Seroprevalence was compared by measuring immunoglobulinG (IgG) against SARS-CoV-2 between October/2020 and May/2021. RESULTS: A total of 550 IMID's patients were studied, all of them on treatment with bDMARDs or tsDMARDs. The seroprevalence of the total patient group was 16% (88/550). Patients receiving therapy with tumor necrosis factor alpha inhibitors (TNFi) had a higher seroprevalence compared to other biologic and synthetic targeted therapies (OR: 1.792 [95%CI: 1.088-2.951]; P=.021). The influence on seroprevalence of concomitant use with b/tsDMARDs of conventional synthetic DMARDs (csDMARDs) was also analyzed. A lower seroprevalence was demonstrated in the group of patients treated with TNFi and methotrexate together, compared with those on TNFi monotherapy, 10.1 vs 24.1% (OR: 0.355 [95%CI: 0.165-0.764]; P=.006). No significant differences were found with the other DMARDs. Regarding IMIDs, no differences in seroprevalence were identified between the different disease groups. CONCLUSION: Patients on treatment with TNFα inhibitors have better humoral response compared to the other b/tsDMARDs. However, when associated with methotrexate the seroprevalence decreases significantly.

Fatal Pulmonary Veno-Occlusive Disease and Systemic Juvenile Idiopathic Arthritis: Case Report and Literature Review / Enfermedad venooclusiva fatal y artritis idiopática juvenil sistémica: caso clínico y revisión de la literatura

Systemic juvenile idiopathic arthritis (sJIA) is a chronic childhood inflammatory disease. SJIA accounts for approximately 5–15 per cent of all cases of JIA and has a high morbidity and mortality rate. In this disease, pulmonary complications (PC) other than pleuritis are much less frequent and not easily recognised by clinicians. Pulmonary hypertension, the most severe PC, is associated with uncontrolled disease and use of biologic therapies. We present a case of a school-age female with sJIA who died of acute cardiopulmonary instability secondary to pulmonary venous-occlusive disease demonstrated by necropsy. We describe her clinical evolution. We also undertook a narrative review of the literature about PC in sJIA to discuss the current state of the art regarding this complication. High disease activity and the use of multiple therapies include disease-modifying anti-rheumatic drugs should be a red flag for clinicians when discounting PC and pulmonary hypertension. The combination of chest X-ray, electrocardiogram and echocardiogram appear to be the best tests to achieve an early diagnosis.(AU)

La artritis idiopática juvenil sistémica (AIJs) es una enfermedad juvenil crónica que representa aproximadamente del 5 al 15% de todos los casos de AIJ y tiene una elevada tasa de morbimortalidad. En esta enfermedad, las complicaciones pulmonares (CP) distintas a pleuritis son mucho menos frecuentes, y no fácilmente reconocibles por los clínicos. La hipertensión pulmonar, la CP más grave, está asociada a la enfermedad incontrolada y el uso de terapias biológicas. Presentamos el caso de una mujer en edad escolar con AIJs que falleció debido a inestabilidad cardiopulmonar aguda secundaria a enfermedad venosooclusiva confirmada en la necropsia. Describimos su evolución clínica, y también realizamos una revisión narrativa de la literatura relativa a CP en AIJs, para debatir los avances más recientes sobre esta complicación. La elevada actividad de la enfermedad y el uso de terapias múltiples que incluyen fármacos antirreumáticos modificadores de la enfermedad deberían servir de signo de alarma a los clínicos para descartar CP e hipertensión pulmonar. La combinación de placas de tórax, electrocardiograma y ecocardiograma parece ser el mejor conjunto de pruebas para lograr un diagnóstico precoz.(AU)

Fatal Pulmonary Veno-Occlusive Disease and Systemic Juvenile Idiopathic Arthritis: Case Report and Literature Review.

Systemic juvenile idiopathic arthritis (sJIA) is a chronic childhood inflammatory disease. SJIA accounts for approximately 5-15 per cent of all cases of JIA and has a high morbidity and mortality rate. In this disease, pulmonary complications (PC) other than pleuritis are much less frequent and not easily recognised by clinicians. Pulmonary hypertension, the most severe PC, is associated with uncontrolled disease and use of biologic therapies. We present a case of a school-age female with sJIA who died of acute cardiopulmonary instability secondary to pulmonary venous-occlusive disease demonstrated by necropsy. We describe her clinical evolution. We also undertook a narrative review of the literature about PC in sJIA to discuss the current state of the art regarding this complication. High disease activity and the use of multiple therapies include disease-modifying anti-rheumatic drugs should be a red flag for clinicians when discounting PC and pulmonary hypertension. The combination of chest X-ray, electrocardiogram and echocardiogram appear to be the best tests to achieve an early diagnosis.

Características de los pacientes con artritis reumatoidea que impactan en la satisfacción y la adherencia al tratamiento: subanálisis de los datos de Argentina, Chile y Uruguay del estudio SENSE / Characteristics of patients with rheumatoid arthritis that impact treatment satisfaction and adherence: subanalysis of data from Argentina, Chile and Uruguay from the SENSE study

Introducción: las necesidades y perspectivas de los pacientes son determinantes para tratar la artritis reumatoidea (AR). Objetivos: evaluar el impacto de la respuesta inadecuada a los fármacos antirreumáticos modificadores de la enfermedad (DMARD) sobre la satisfacción con el tratamiento, los resultados y las perspectivas de pacientes adultos con control inadecuado de la AR de actividad moderada/alta. Materiales y métodos: se evaluó la satisfacción mediante el cuestionario Treatment Satisfaction Questionnaire for Medication (TSQM) v1.4. Se recolectaron datos sobre la calidad de vida, la adherencia y las estrategias de manejo. Se presentan los resultados para Argentina, Chile y Uruguay (n=202). Resultados: el promedio de la escala de satisfacción global TSQM fue de 62,3±21,8. El 83% informó buena adherencia. Las principales expectativas del tratamiento fueron "alivio duradero de los síntomas" y "menos dolor articular". El 53,47% prefirió tratamiento oral y el 75,74% eligió un rápido inicio de acción. El efecto secundario menos aceptado fue "mayor riesgo de neoplasias". Se planificó rotar el DMARD en el 55% de los casos. De estos, el 84,7% se consideraron terapias avanzadas. La mayoría estaba abierto a un esquema combinado, pero el 25,2% prefirió no utilizarlo. Conclusiones: los resultados reafirman el compromiso con las estrategias treat-to-target, considerando la individualización de las decisiones terapéuticas en el contexto regional.

Introduction: patients' needs and perspectives are determinants for the treatment of rheumatoid arthritis (RA). Objectives: to evaluate the impact of inadequate response to disease-modifying antirheumatic drugs (DMARDs) on treatment satisfaction, outcomes and perspectives of adult patients with inadequate control of moderate/high activity RA. Materials and methods: satisfaction was assessed using the TSQM v1.4 questionnaire. Data on quality of life, adherence and management strategies were collected. Results are presented for Argentina, Chile and Uruguay (n=202). Results: the mean of the TSQM global satisfaction score was 62.3±21.8. Eighty-three percent reported good adherence. The main expectations of treatment were "lasting relief of symptoms" and "less joint pain". The 53.47% of patients preferred an oral treatment; 75.74% chose a rapid onset of action. The least accepted side effect was "increased risk of malignant neoplasms". Fifty-five percent planned to rotate DMARD. Of these, advanced therapies were considered in only 84.7%. Most were open to a combination treatment, but 25.2% preferred not to use it. Conclusions: the results reaffirm the commitment to treat-to-target strategies, considering the individualization of therapeutic decisions in the regional context.

Manejo clínico y discontinuación de tratamiento en pacientes con artritis reumatoide de inicio en una consulta de Reumatología / Clinical Management and Discontinuation of Treatment in Patients with Recent Onset Rheumatoid Arthritis in a Rheumatology Consultation

Introducción: El tratamiento de la artritis reumatoide ha cambiado drásticamente en los últimos años, sobre todo con el uso de los fármacos modificadores de la enfermedad (FAME). Los datos sobre el manejo de esta enfermedad en ensayo clínico son abundantes, pero no en la vida real. El objetivo de nuestro estudio es describir el manejo de una cohorte de artritis reumatoide de inicio en práctica clínica diaria, especialmente las suspensiones de los FAME y sus causas. Métodos: Estudio observacional retrospectivo de pacientes con artritis reumatoide diagnosticados entre 01/07 y 12/14 seguidos hasta 01/17, que usaron>1 FAME≥3 meses. Variables: sociodemográficas, clínicas, tratamiento, suspensión del FAME y causa. Análisis descriptivo de las características sociodemográficas, clínicas y de tratamiento. Incidencia de suspensión (IS) por técnicas de supervivencia, expresándose en 100 pacientes/año con intervalo de confianza del 95%. Resultados: Se incluyen 814 pacientes con 2.388 cursos de tratamiento, el 77% mujeres, edad media 57,5 años. Primer curso: monoterapia (92,75%), especialmente metotrexate (56,06%). En posteriores cursos aumentan terapia combinada y uso de biológico (principalmente etanercept). Se registraron 1.094 suspensiones (29,5 [27,8-31,3]). La IS fue mayor para evento adverso (15,9 [14,7-17,3]), biológicos (49,6 [43,1-57,2]) y terapia combinada. El FAME con menor IS fue metotrexate (25,8 [23,8-28,1]). Conclusión: El metotrexate fue el fármaco más utilizado, el biológico aumentó a lo largo del seguimiento, siendo el más frecuente etanercept. La IS de los FAME fue 29/100 pacientes año, principalmente por evento adverso. Parece mayor en las terapias que incluyen biológicos y en las combinadas. El metotrexate es el fármaco con menor IS.(AU)

Introduction: The treatment of rheumatoid arthritis has changed dramatically in recent years, especially with the use of disease modifying drugs (DMARDs). Data on the management of this disease in clinical trials are abundant, but not so in real life. The aim of our study is to describe the management of an early rheumatoid arthritis cohort in daily clinical practice, especially DMARD discontinuations and reasons. Methods: A retrospective observational study of patients with rheumatoid arthritis diagnosed between 01/07 and 12/14 followed up to 01/17, using>1 DMARD≥3 months. Variables: sociodemographic, clinical, treatment, DMARD discontinuation and reason. Descriptive analysis of sociodemographic, clinical and treatment characteristics. Discontinuation incidence rate (DIR) due to survival techniques, expressed in 100 patients/year with 95% confidence interval. Results: 814 patients were included with 2,388 courses of treatment, 77% women, mean age 57.5 years. First course: monotherapy (92.75%), especially methotrexate (56.06%). In later courses there was increased combined therapy and use of biologicals (mainly etanercept). There were 1,094 discontinuations (29.5 [27.8-31.3]). The DIR was higher for adverse events (15.9 [14.7-17.3]), biologicals (49.6 [43.1-57.2]) and combined therapy. The DMAR with the lowest DIR was methotrexate (25.8 [23.8-28.1]). Conclusion: Methotrexate was the most used drug, biologicals increased throughout the follow-up, the most frequent being Etanercept. The DMARD DIR was 29/100 patients per year, mainly due to adverse events. It seems to be higher in the therapies that include biologicals and combined therapies. Methotrexate is the drug with the lowest DIR.(AU)

Clinical management and discontinuation of treatment in patients with recent onset rheumatoid arthritis in a rheumatology consultation.

INTRODUCTION: The treatment of Rheumatoid Arthritis (RA) has changed dramatically in recent years, especially with the use of disease modifying drugs (DMARDs). Data on the management of this disease in clinical trials are abundant, but not so in real life. The aim of our study is to describe the management of an early RA cohort in daily clinical practice, especially DMARD discontinuations and reasons. METHODS: A retrospective observational study of patients with RA diagnosed between 01/07 and 12/14 followed up to 01/17, using >1 DMARD ≥ 3 months. VARIABLES: sociodemographic, clinical, treatment, DMARD discontinuation and reason. Descriptive analysis of sociodemographic, clinical and treatment characteristics. Discontinuation incidence rate (DIR) due to survival techniques, expressed in 100 patients*year with 95% confidence interval. RESULTS: 814 patients were included with 2388 courses of treatment, 77% women, mean age 57.5 years. First course: monotherapy (92.75%), especially Methotrexate (56.06%). In later courses there was increased combined therapy and use of biologicals (mainly Etanercept). There were 1094 discontinuations (29.5 [27.8-31.3]). The DIR was higher for adverse events (15.9 [14.7-17.3]), biologicals (49.6 [43.1-57.2]) and combined therapy. The DMAR with the lowest DIR was MTX (25.8 [23.8-28.1]). CONCLUSION: Methotrexate was the most used drug, biologicals increased throughout the follow-up, the most frequent being Etanercept. The DMARD DIR was 29*100 patients per year, mainly due to adverse events. It seems to be higher in the therapies that include biologicals and combined therapies. MTX is the drug with the lowest DIR.

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)

Is Palindromic Rheumatism a Pre-rheumatoid Arthritis Condition? Low Incidence of Rheumatoid Arthritis in Palindromic Rheumatism Patients Treated with Tight Control Strategy / ¿Es el reumatismo palindrómico una condición de artritis pre-reumatoide? Baja incidencia de artritis reumatoide en pacientes con reumatismo palindrómico tratados con estrategia de control estricta

Objectives: Palindromic rheumatism (PR) is characterized by repetitive, afebrile episodes of acute arthritis and peri-arthritis. The aim of this study was considering the long-term outcomes of patients with PR who were treated with tight control strategy using Disease-modifying anti-rheumatic drugs (DMARDs). Methods: We reviewed the charts of 106 patients diagnosed with PR who were referred to the Connective Tissue Diseases Research Center (CTDRC). We recruited all the patients diagnosed with PR according to the criteria of Hannonen. They visited the CTDRC clinic regularly and were treated with hydroxychloroquine and low dose prednisolone because of active episodes of PR. In cases that the attacks did not come under control in 3–6 months, methotrexate was added or replaced and the dose was increased up to 25mg/week. In resistant cases, sulfasalazine was added, followed by the addition of leflunomide and then azathioprine. Disease outcome was evaluated by getting complete or partial remission and prevention of disease evolution to rheumatoid arthritis (RA) or other inflammatory connective tissue diseases. Results: This study included 92 patients with PR who were treated with DMARDs. Attacks were controlled completely or partially in 76 (82.6%) patients. Medications free remission was obtained in 16.3% of the patients. RA developed in 8.7% of the patients. By multivariate logistic regression analysis, age ≤40 at disease presentation, non-adherence to therapy and PIP joints involvement were the only factors which independently predicted the risk of treatment failure. Conclusions: Tight control strategy by using DMARDs may control PR and prevent disease progression to RA.(AU)

Objetivos: El reumatismo palindrómico (PR) se caracteriza por episodios repetitivos y afebriles de artritis aguda y periartritis. El objetivo de este estudio fue considerar los resultados a largo plazo de los pacientes con PR que fueron tratados con una estrategia de control estricta utilizando fármacos antirreumáticos modificadores de la enfermedad (DMARD). Métodos: Revisamos los cuadros de 106 pacientes diagnosticados con PR que fueron remitidos al Centro de Investigación de Enfermedades de Tejido Conectivo (CTDRC). Reclutamos a todos los pacientes diagnosticados con PR según los criterios de Hannonen. Visitaron la clínica de CTDRC regularmente y fueron tratados con hidroxicloroquina y prednisolona a dosis bajas debido a episodios activos de PR. En los casos en que los ataques no se controlaron en 3 a 6 meses, se agregó o reemplazó metotrexato y la dosis se aumentó hasta 25mg/semana. En casos resistentes, se añadió sulfasalazina, seguido de la adición de leflunomida y luego azatioprina. El resultado de la enfermedad se evaluó obteniendo la remisión completa o parcial y la prevención de la evolución de la enfermedad a la artritis reumatoide (AR) u otras enfermedades inflamatorias del tejido conectivo. Resultados: Este estudio incluyó 92 pacientes con PR que fueron tratados con DMARD. Los ataques fueron controlados total o parcialmente en 76 (82,6%) pacientes. La remisión libre de medicamentos se obtuvo en el 16,3% de los pacientes. La AR se desarrolló en el 8,7% de los pacientes. Mediante el análisis de regresión logística multivariante, la edad ≤40 en la presentación de la enfermedad, la no adhesión al tratamiento y la afectación de las articulaciones PIP fueron los únicos factores que predijeron de forma independiente el riesgo de fracaso del tratamiento. Conclusiones: Una estrategia de control estricta mediante el uso de DMARD puede controlar la RP y prevenir la progresión de la enfermedad a AR.(AU)

Is Palindromic Rheumatism a Pre-rheumatoid Arthritis Condition? Low Incidence of Rheumatoid Arthritis in Palindromic Rheumatism Patients Treated with Tight Control Strategy.

OBJECTIVES: Palindromic rheumatism (PR) is characterized by repetitive, afebrile episodes of acute arthritis and peri-arthritis. The aim of this study was considering the long-term outcomes of patients with PR who were treated with tight control strategy using Disease-modifying anti-rheumatic drugs (DMARDs). METHODS: We reviewed the charts of 106 patients diagnosed with PR who were referred to the Connective Tissue Diseases Research Center (CTDRC). We recruited all the patients diagnosed with PR according to the criteria of Hannonen. They visited the CTDRC clinic regularly and were treated with hydroxychloroquine and low dose prednisolone because of active episodes of PR. In cases that the attacks did not come under control in 3-6 months, methotrexate was added or replaced and the dose was increased up to 25mg/week. In resistant cases, sulfasalazine was added, followed by the addition of leflunomide and then azathioprine. Disease outcome was evaluated by getting complete or partial remission and prevention of disease evolution to rheumatoid arthritis (RA) or other inflammatory connective tissue diseases. RESULTS: This study included 92 patients with PR who were treated with DMARDs. Attacks were controlled completely or partially in 76 (82.6%) patients. Medications free remission was obtained in 16.3% of the patients. RA developed in 8.7% of the patients. By multivariate logistic regression analysis, age ≤40 at disease presentation, non-adherence to therapy and PIP joints involvement were the only factors which independently predicted the risk of treatment failure. CONCLUSIONS: Tight control strategy by using DMARDs may control PR and prevent disease progression to RA.

Intravenous tocilizumab in the management of rheumatoid arthritis: Clinical practice findings from a 6-month international, multicentre, observational study in Central America and the Caribbean / El tocilizumab intravenoso en el tratamiento de la artritis reumatoide: resultados de la práctica clínica de un estudio internacional, multicéntrico y observacional de 6 meses de duración en América Central y el Caribe

ABSTRACT Tocilizumab (TCZ), an 1interieukin-6 receptor-α Inhibitor, is Indicated in patients with moderate to severe rheumatoid arthritis with inadequate response to disease modifying drugs. ACT UP is a multinational project co11ecting information from severa1 post-marketing TCZ studies. Aim: To determine the proportion of patients in the routine clinical care setting receiving intravenous TCZ after 6 months treatment. Identification of TCZ treatment patterns, efficacy, and safety were also recorded. Method: This prospective non-interventional 6-month study, collected real-world information from 169 Central American and Caribbean patients. No interventional procedures or additional visits outside routine clinical care practice were performed. Statistical analysis was essentially descriptive. Results: Adherence rate was 74.0%, with 97% of patients receiving TCZ as first biological therapy line and there were no deviations from the local label. Almost 85% of patients started with combination therapy, and the majority remained under this scheme throughout the study. A significant decrease in disease activity assessments and acute phase reactants values were detected during TCZ treatment. The percentage of patients that achieved improvement according to the different levels of the American College of Rheumatology (ACR) increased during the study, and relevant enhancements in quality of life were also accomplished. Adverse events (AEs) occurred in 35 patients, with metabolic and nutritional disorders being the most common. Serious AEs were reported in 3% of patients, and special interest AEs occurred in 6 patients. Conclusion: Treatment adherence was mainly determined by follow-up and compliance with the administration schedule. Efficacy analysis showed better results than those reported in international literature. The incidence of AEs was also lower than in previously published data.

RESUMEN El tocilizumab (TCZ) está indicado en la artritis reumatoide moderada a severa, principalmente en respuestas inadecuadas a fármacos convencionales. ACT UP es un proyecto multinacional que recopila información relacionada con varios estudios de poscomercialización. Objetivo: Determinar la proporción de pacientes en la atención clínica de rutina que continúan en tratamiento con TCZ intravenoso después de 6 meses. Se llevó a cabo la identificación de patrones de administración, eficacia y seguridad. Método: Este estudio observacional prospectivo recopiló información de la vida real de 169 pacientes de América Central y el Caribe. No se hicieron intervenciones ni visitas adicionales fuera de la práctica clínica habitual. El análisis estadístico fue esencialmente descriptivo. Resultados: La tasa de adherencia al tratamiento fue del 74,0%, el 97% de los pacientes reci bieron TCZ como primera línea biológica y no existieron desviaciones en las indicaciones de administración según el inserto local. Aproximadamente el 85% de los pacientes inició TCZ como terapia combinada, y la mayoría permaneció bajo este esquema. Se evidenció una dis minución en la actividad de la enfermedad y un aumento en el porcentaje de pacientes que lograron respuesta según los diferentes grados del Colegio Americano de Reumatología. En 35 pacientes se presentaron eventos adversos (EA), siendo los relacionados con metabolismo y nutrición los más comunes. Se informaron EA graves en el 3% de los pacientes y de interés especial en 6 casos. Conclusión: El seguimiento de los pacientes y el cumplimiento del programa fueron los prin cipales determinantes en la adherencia. El análisis de eficacia mostró mejores resultados que los reportados previamente y la incidencia de EA fue menor que en otros estudios.

Clinical Management and Discontinuation of Treatment in Patients with Recent Onset Rheumatoid Arthritis in a Rheumatology Consultation. / Manejo clínico y discontinuación de tratamiento en pacientes con artritis reumatoide de inicio en una consulta de Reumatología.

INTRODUCTION: The treatment of rheumatoid arthritis has changed dramatically in recent years, especially with the use of disease modifying drugs (DMARDs). Data on the management of this disease in clinical trials are abundant, but not so in real life. The aim of our study is to describe the management of an early rheumatoid arthritis cohort in daily clinical practice, especially DMARD discontinuations and reasons. METHODS: A retrospective observational study of patients with rheumatoid arthritis diagnosed between 01/07 and 12/14 followed up to 01/17, using>1 DMARD≥3 months. VARIABLES: sociodemographic, clinical, treatment, DMARD discontinuation and reason. Descriptive analysis of sociodemographic, clinical and treatment characteristics. Discontinuation incidence rate (DIR) due to survival techniques, expressed in 100 patients/year with 95% confidence interval. RESULTS: 814 patients were included with 2,388 courses of treatment, 77% women, mean age 57.5 years. First course: monotherapy (92.75%), especially methotrexate (56.06%). In later courses there was increased combined therapy and use of biologicals (mainly etanercept). There were 1,094 discontinuations (29.5 [27.8-31.3]). The DIR was higher for adverse events (15.9 [14.7-17.3]), biologicals (49.6 [43.1-57.2]) and combined therapy. The DMAR with the lowest DIR was methotrexate (25.8 [23.8-28.1]). CONCLUSION: Methotrexate was the most used drug, biologicals increased throughout the follow-up, the most frequent being Etanercept. The DMARD DIR was 29/100 patients per year, mainly due to adverse events. It seems to be higher in the therapies that include biologicals and combined therapies. Methotrexate is the drug with the lowest DIR.

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.

Subclinical synovitis and tenosynovitis by ultrasonography (US) 7 score in patients with rheumatoid arthritis treated with synthetic drugs, in clinical remission by DAS28.

OBJECTIVE: To identify synovitis and tenosynovitis active by using the Ultrasound 7 (US 7) scoring system in patients with rheumatoid arthritis (RA) in clinical remission induced by synthetic disease-modifying antirheumatic drugs (DMARDs). METHODS: This is a multicentric, cross-sectional, observational study including 94 RA patients >18 years old who were in remission as defined by the 28-joints disease activity score (DAS28) <2.6 induced by synthetic DMARD during at least 6 months. Patients with a previous or current history of biologic DMARD treatment were not included in the study. Demographic and clinical data were collected by the local rheumatologist; the US evaluation was performed by a calibrated rheumatologist, who intended to detect grayscale synovitis and power Doppler (PD) using the 7-joint scale. Intra and inter-reader exercises of images between 2 ultrasonographers were realized. RESULTS: Patients' mean age was 49.1±13.7 years; 83% were women. The mean disease duration was 8±7 years and remission lasted for 27.5±31.8 months. The mean DAS28 score was 1.9±0.66. Grayscale synovitis was present in 94% of cases; it was mild in 87.5% and moderate in 12.5%. Only 12.8% of the patients had PD. The metatarsophalangeal, metacarpophalangeal, and carpal joints of the dominant hand were the joints more frequently affected by synovitis. Tenosynovitis by grayscale was observed in 9 patients (9.6%). The intra and inter-reading kappa value were 0.77, p<0.003 (CI 95%, 0.34-0.81) and 0.81, p<0.0001 (CI 95%, 0.27-0.83) respectively. CONCLUSIONS: Low percentage of synovitis and tenosynovitis active were founded according to PD US by 7 score in RA patients under synthetic DMARDs during long remission. This score has benefit because evaluate tenosynovitis, another element of subclinical disease activity.

Effectiveness of conventional disease-modifying antirheumatic drugs in psoriatic arthritis: A systematic review. / Eficacia de los fármacos antirreumáticos modificadores de la enfermedad sintéticos en artritis psoriásica: una revisión sistemática.

BACKGROUND: Due to the clinical heterogeneity of psoriatic arthritis (PsA), recommendations have been developed by international groups to guide therapeutic decisions of the rheumatologist. The objective of the current systematic review (RS) was to evaluate the evidence of efficacy of disease-modifying antirheumatic drugs (DMARDs) in PsA. METHODS: Literature search in Medline, EMBASE, Cochrane Library, from 2008 to 2014. We included RS, randomized clinical trials and observational studies, in patients with PsA and an evaluation of efficiency of conventional DMARDs (methotrexate, sulfasalazine, leflunomide), according to the following outcomes: peripheral and axial symptoms; peripheral radiological damage; enthesitis according to power Doppler ultrasound or magnetic resonance imaging (enthesitis count before and after therapy); dactylitis; uveitis. RESULTS: Title and abstract were used to retrieve 1,662 documents for this review (Medline, n=433; EMBASE n=1,132; Cochrane, n=97), and 48 studies were selected for detailed reading; finally, 8 studies were included. CONCLUSIONS: Since the studies included are not robust, and there are arguments to support the effectiveness of methotrexate, the evidence observed with the treatment of DMARDs in PsA is not conclusive.

Recommendations of the Spanish Society of Rheumatology on treatment and use of systemic biological and non-biological therapies in psoriatic arthritis. / Recomendaciones de la Sociedad Española de Reumatología sobre el tratamiento y uso de terapias sistémicas biológicas y no biológicas en artritis psoriásica.

OBJECTIVE: The main purpose of this recommendation statement is to provide clinicians with the best available evidence and the best opinion agreed upon by the panelists for a rational use of synthetic disease modifying antirheumatic drugs (DMARDs) and biologicals in psoriatic arthritis (PsA) patients. The present document also focuses on important aspects in the management of PsA, such as early diagnosis, therapeutic objectives, comorbidities and optimization of treatment. METHODS: The recommendations were agreed by consensus by a panel of 8 expert rheumatologists, previously selected by the Spanish Society of Rheumatology (SER) through an open call. The phases of the work were: identification of key areas for updating the previous consensus, analysis and synthesis of scientific evidence (modified Oxford system, Centre for Evidence-based Medicine, 2009) and formulation of recommendations based on this evidence and by consensus techniques. RESULTS: Seventeen recommendations were issued for the treatment of PsA patients. Six of them were of general nature, ranging from the early diagnosis and treatment to the importance of assessing comorbidities. The other 11 were focused on the indications for DMARDs and biological therapy in the distinct clinical forms of the disease. Likewise, the situation of failure of the first biological is addressed and treatment algorithms and a table with the different biological therapies are also included. CONCLUSIONS: We present the update of SER recommendations for the treatment of PsA with DMARDs and biologics.

Two-year efficacy of tocilizumab in patients with active rheumatoid arthritis in clinical practice. / Eficacia a 2 años de tocilizumab en pacientes con artritis reumatoide activa en la práctica clínica habitual.

OBJECTIVES: To evaluate the efficacy of tocilizumab (TCZ) in patients with rheumatoid arthritis (RA) in clinical practice, retention rates of the drug and predictors of response. METHODS: We performed a descriptive, prospective, longitudinal, open-label study in patients receiving TCZ (8mg/kg/4 weeks) in a clinical practice setting. The clinical responses were evaluated using the European League Against Rheumatism (EULAR) response criteria, and the low activity and remission rates according to the Disease Activity Score 28-erythrocyte sedimentation rate (DAS28-ESR) and the Clinical Disease Activity Index (CDAI). RESULTS: The EULAR response rate was 86.63% and the DAS28 remission rate was 53.7% after 6 months of treatment; rates of low disease activity were 52.9% on CDAI and 47.1% on DAS28 at month 24. There were no statistically significant differences in EULAR response, rates of low activity and remission on DAS28 between patients receiving TCZ alone and those receiving TCZ in combination therapy, or between patients positive or negative for rheumatoid factor (RF) and/or anti-cyclic citrullinated peptide (anti-CCP) antibodies. The naïve biological therapy patients showed better remission and low activity rates after 6 months of treatment. The retention rate was 61% at month 24. Adverse events were among the most frequent causes of discontinuation. CONCLUSIONS: Tocilizumab is effective in RA, has a similar efficacy when used alone or in combination with synthetic disease-modifying antirheumatic drugs (DMARDs) and shows high retention rates.

Recommendations by the Spanish Society of Rheumatology for the management of patients diagnosed with rheumatoid arthritis who cannot be treated with methotrexate. / Documento de Recomendaciones de la Sociedad Española de Reumatología para el manejo clínico del paciente con artritis reumatoide que no puede utilizar metotrexato.

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