No es el mismo pero ¿es igual? Cycling de agentes biológicos en artritis reumatoide. Experiencia en el Instituto Mexicano del Seguro Social / Not the same, but is it the same? Cycling of biologic agents in rheumatoid arthritis. Experience in the Instituto Mexicano del Seguro Social

Introducción: Los datos disponibles para los biocomparables comercializados actualmente no son concluyentes con respecto al potencial impacto del cambio por razones no médicas sobre la eficacia, la seguridad y la inmunogenicidad en los pacientes. En el futuro se expandirán las opciones de tratamiento biológico, biocomparable, no bio-comparables y otros de síntesis química, por lo que es importante conocer cómo se comporta la persistencia al tratamiento tras un cambio por razón no médica, que ya ocurre como un hecho habitual en los servicios médicos de seguridad social en México, ya que esto nos ayudará a entender los mejores estándares de tratamiento para pacientes con enfermedades inmunomediadas crónicas. Objetivos: El objetivo primario fue evaluar el impacto del cambio por razón no médica en pacientes con artritis reumatoide (AR) estables tratados con biológico innovador sobre la persistencia en el tratamiento, después de cambiar a un biocomparable o a un no biocomparable, en relación con los pacientes que continúan con el biológico innovador. Diseño del estudio: Estudio observacional (no intervencionista) de cohortes emparejado donde se comparó una cohorte histórica obtenida por la revisión de historias médicas de pacientes estables que no fueron cambiados de tratamiento por al menos 6meses, con dos cohortes de pacientes que fueron cambiados de tratamiento por razones no médicas a otro fármaco con la misma diana terapéutica (cycling). Resultados: Se incluyeron 264 pacientes con diagnóstico de AR (ACR/EULAR, 2010): 132 pacientes que fueron cambiados de tratamiento por razones no médicas por un fármaco de mecanismo similar de acción y 132 pacientes que no fueron cambiados de tratamiento. De los 264 pacientes participantes en el estudio, 230 pacientes (87,1%) corresponden al sexo femenino. El promedio de edad fue de 53,9años, la edad mínima 16años y la máxima 84 años. (AU)

Introduction: Available data for biocomparable drugs are not enough to make clear decisions with respect to the potential consequences of a change for non-medical reasons in efficacy, security and inmunogenicity in patients. In the near future, options on biological treatments, biocomparable drugs, non biocomparable drugs and new chemical synthesis options will grow. Therefore, it is important to know how patients behave in persistence of treatment after a change for non-medical reasons, which already happens on a regular basis in social security institutions in Mexico. This information will help us to better understand the standard of treatment for patients with chronic immunomediated conditions. Objective: The primary objective was to measure the impact of change for non-medical reasons in patients with rheumatoid arthritis (RA) treated with an innovative biological on persistence of treatment after changing to a biocomparable drug or a non-biocomparable drug, compared with those patients staying with the innovative biological. Study design: This is an observational study (non-interventionist) of paired cohorts, where an historic cohort obtained by review of clinical records of stable patients in which no modifications to treatment were made for at least six months is compared with two cohorts of patients whose treatments were switched to another treatment with the same therapeutic mechanism for-non-medical reasons (cycling). Results: We included 264 RA patients (ACR/EULAR, 2010); 132 were switched for non-medical reasons, and 132 were not switched. Two-hundred and thirty (87.1%) were female. Average age was 53.9years, ranging from 16 to 84years. Two-hundred and sixty-three patients were Latino (99.6%); one was Caucasian.(AU)

Not the same, but is it the same? Cycling of biologic agents in rheumatoid arthritis. Experience in the Instituto Mexicano del Seguro Social.

INTRODUCTION: Available data for biocomparable drugs are not enough to make clear decisions with respect to the potential consequences of a change for non-medical reasons in efficacy, security and inmunogenicity in patients. In the near future, options on biological treatments, biocomparable drugs, non biocomparable drugs and new chemical synthesis options will grow. Therefore, it is important to know how patients behave in persistence of treatment after a change for non- medical reasons, which already happens on a regular basis in social security institutions in Mexico. This information will help us to better understand the standard of treatment for patients with chronic immunomediated conditions. OBJECTIVE: The primary objective was to measure the impact of change for non-medical reasons in patients with rheumatoid arthritis (RA) treated with an innovative biological on persistence of treatment after changing to a biocomparable drug or a non-biocomparable drug, compared with those patients staying with the innovative biological. STUDY DESIGN: This is an observational study (non-interventionist) of paired cohorts, where an historic cohort obtained by review of clinical records of stable patients in which no modifications to treatment were made for at least six months is compared with two cohorts of patients whose treatments were switched to another treatment with the same therapeutic mechanism for-non-medical reasons (cycling). RESULTS: We included 264 RA patients (ACR/EULAR, 2010); 132 were switched for non-medical reasons, and 132 were not switched. Two-hundred and thirty (87.1%) were female. Average age was 53.9 years, ranging from 16 to 84 years. Two-hundred and sixty-three patients were Latino (99.6%); one was Caucasian. Persistence of treatment 12 months after the change was 84.8% (85.8% in Enbrel/Infinitam, 78.9% for Remicade/Remsima). No statistical difference was found with respect to RA clinical activity measured by DAS28 12 months after the switch (P > .05). In the 134 switched patients, 20 discontinued the new treatment due to lack of efficacy of the new drug and were changed to a different drug with a different biologic target. Although no differences were found in the cohorts of switched patients with respect to DAS 28 after 12 months of use, we did find differences in the frequency of adverse events. Forty-two patients had an adverse event in the drug switch cohorts: 33 in the Enbrel-Infinitam group and 9 in the Remicade-Remsima group. CONCLUSIONS: The persistence of treatment after switching from an innovative drug to a biocomparable or a non- biocomparable in RA patients did not show statistically significative differences in our cohorts, but we did find a higher number of adverse events when comparing those who were changed with those who continued on an innovative drug. Twenty patients in the switch groups had to receive a new drug with a different biological target due to lack of efficacy of the switched drug.

Not the same, but ¿is it the same? Cycling of biologic agents in rheumatoid arthritis. Experience in the Instituto Mexicano del Seguro Social. / No es el mismo pero ¿es igual? Cycling de agentes biológicos en artritis reumatoide. Experiencia en el Instituto Mexicano del Seguro Social.

INTRODUCTION: Available data for biocomparable drugs are not enough to make clear decisions with respect to the potential consequences of a change for non-medical reasons in efficacy, security and inmunogenicity in patients. In the near future, options on biological treatments, biocomparable drugs, non biocomparable drugs and new chemical synthesis options will grow. Therefore, it is important to know how patients behave in persistence of treatment after a change for non-medical reasons, which already happens on a regular basis in social security institutions in Mexico. This information will help us to better understand the standard of treatment for patients with chronic immunomediated conditions. OBJECTIVE: The primary objective was to measure the impact of change for non-medical reasons in patients with rheumatoid arthritis (RA) treated with an innovative biological on persistence of treatment after changing to a biocomparable drug or a non-biocomparable drug, compared with those patients staying with the innovative biological. STUDY DESIGN: This is an observational study (non-interventionist) of paired cohorts, where an historic cohort obtained by review of clinical records of stable patients in which no modifications to treatment were made for at least six months is compared with two cohorts of patients whose treatments were switched to another treatment with the same therapeutic mechanism for-non-medical reasons (cycling). RESULTS: We included 264 RA patients (ACR/EULAR, 2010); 132 were switched for non-medical reasons, and 132 were not switched. Two-hundred and thirty (87.1%) were female. Average age was 53.9years, ranging from 16 to 84years. Two-hundred and sixty-three patients were Latino (99.6%); one was Caucasian. Persistence of treatment 12months after the change was 84.8% (85.8% in Enbrel/Infinitam, 78.9% for Remicade/Remsima). No statistical difference was found with respect to RA clinical activity measured by DAS28 12months after the switch (P>.05). In the 134 switched patients, 20 discontinued the new treatment due to lack of efficacy of the new drug and were changed to a different drug with a different biologic target. Although no differences were found in the cohorts of switched patients with respect to DAS28 after 12months of use, we did find differences in the frequency of adverse events. Forty-two patients had an adverse event in the drug switch cohorts: 33 in the Enbrel-Infinitam group and 9 in the Remicade-Remsima group. CONCLUSIONS: The persistence of treatment after switching from an innovative drug to a biocomparable or a non-biocomparable in RA patients did not show statistically significative differences in our cohorts, but we did find a higher number of adverse events when comparing those who were changed with those who continued on an innovative drug. Twenty patients in the switch groups had to receive a new drug with a different biological target due to lack of efficacy of the switched drug.

Role of depressive symptoms in the health-related quality of life of Venezuelan patients with rheumatoid arthritis. Results from a tertiary care center.

INTRODUCTION/OBJECTIVE: To examine the effect of depressive symptoms on health-related quality of life (HR-QoL) in Venezuelan patients with rheumatoid arthritis (RA). METHODS: HR-QoL was assessed in a cross-sectional, single-center study of 212 consecutive Venezuelan patients with RA (1987 American College of Rheumatology criteria) using the Medical Outcomes Study Short Form (SF-36), which includes a Physical Composite Scale (PCS) and a Mental Composite Scale (MCS); depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale. Covariates included socio-demographics, comorbidities, disease characteristics, body mass index, and disability. Unadjusted and multivariable linear regression analysis were used to determine the effect of depressive symptoms on HR-QoL. RESULTS: Mean age was 50.2 years and 89.6% were female. Twenty-five percent of patients had depressive symptoms. In the multivariable regression analysis, the presence of depressive symptoms changed the mental SF-36 scores by - 4.81 (p = 0.0052) and the physical SF-36 scores by - 3.33 (p = 0.0527). Other factors significantly associated with scores on the PCS of the SF-36 were functional class, disability and job loss due to RA. CONCLUSIONS: The presence of depressive symptoms negatively affected the HR-QoL in our patients, with a predominant effect on the MCS of the SF-36. The PCS of the SF-36 was mainly affected by those symptoms related to the functional impairment and inflammatory activity of the disease. The routine assessment and early treatment of depressive symptoms, targeting mental and mood manifestations, may improve the HR-QoL and thus contribute to healthier outcomes in Venezuelan RA patients.

Subclinical synovitis measured by ultrasound in rheumatoid arthritis patients with clinical remission induced by synthetic and biological modifying disease drugs / Sinovitis subclínica medida por ultrasonido en pacientes con artritis reumatoide en remisión clínica inducida por fármacos modificadores de la enfermedad sintéticos y biológicos

Background: Rheumatoid arthritis (RA) patients with disease in clinical remission might show subclinical synovitis, which can be related to the progress of structural joint damage. Objective: To determine and compare the degree of synovial inflammation by ultrasound (US) in patients with RA in clinical remission, treated with DMARD or combination therapy with DMARD and anti-TNF. Methods: Hospital-based cross-sectional study of 58 patients with RA in sustained remission for at least 6 months by DAS28 <2.6, who attended the Rheumatology Service at the Hospital Universitario de Caracas. Patients underwent clinical, functional, and laboratory assessments. Ultrasound was performed in hands measuring synovial effusion, synovial hypertrophy and power Doppler signal; using a semiquantitative 4-point scale of 0=none to 3=severe. Chi-square and t-test were used to compare the clinical, functional, laboratory and US assessments between the DMARD (N=37) and combination therapy with DMARD and anti-TNF (N=21) groups. A p-value <0.05 was considered statistically significant. Results: Out of 58 patients, 25.9% had remission by US and 74.1% had synovial effusion or hypertrophy or positive power Doppler signal. Non-significant differences in US synovitis between the two groups were found. Conclusions: Persistent US activity was evident in a high percentage of rheumatoid arthritis patients in clinical remission by DAS28. No differences in subclinical synovitis measured by US were found between patients with DMARD and anti-TNF-induced clinical remission

Introducción: Los pacientes con artritis reumatoide (AR) con enfermedad en remisión clínica pueden mostrar sinovitis subclínica, que puede estar relacionada con el progreso del daño articular estructural. Objetivos: Determinar y comparar el grado de inflamación sinovial medida por ultrasonido (US) en pacientes con AR en remisión clínica, tratados con FAME o FAME y anti-TNF. Métodos: Estudio transversal con sede en hospital, donde se evaluaron 58 pacientes con AR en remisión sostenida durante al menos 6 meses por DAS28<2,6, que asistieron al Servicio de Reumatología del Hospital Universitario de Caracas. Se realizó evaluación clínica, funcional y de laboratorio. Se practicó US en manos evaluando derrame, hipertrofia sinovial y presencia de señal power Doppler, utilizando una escala semicuantitativa de 4 puntos 0=ninguno a 3=severo. Se compararon los hallazgos entre los pacientes con FAME (n=37) y FAME y anti-TNF (n=21), utilizando las pruebas de Chi-cuadrado y t de Student. Se consideró significación estadística si el valor de p era<0,05. Resultados: De los 58 pacientes, el 25,9% tuvo remisión por US y el 74,1% presentó derrame, hipertrofia sinovial o señal power Doppler positiva. No hubo diferencias significativas en la presencia de sinovitis medida por US entre los 2 grupos. Conclusiones: En pacientes en remisión clínica por DAS28, la actividad persistente medida por US fue evidente en un alto porcentaje. No hubo diferencias en la sinovitis subclínica medida por US entre los pacientes en remisión clínica inducida con FAME y FAME y anti-TNF

Subclinical synovitis measured by ultrasound in rheumatoid arthritis patients with clinical remission induced by synthetic and biological modifying disease drugs.

BACKGROUND: Rheumatoid arthritis (RA) patients with disease in clinical remission might show subclinical synovitis, which can be related to the progress of structural joint damage. OBJECTIVE: To determine and compare the degree of synovial inflammation by ultrasound (US) in patients with RA in clinical remission, treated with DMARD or combination therapy with DMARD and anti-TNF. METHODS: Hospital-based cross-sectional study of 58 patients with RA in sustained remission for at least 6 months by DAS28 <2.6, who attended the Rheumatology Service at the Hospital Universitario de Caracas. Patients underwent clinical, functional, and laboratory assessments. Ultrasound was performed in hands measuring synovial effusion, synovial hypertrophy and power Doppler signal; using a semiquantitative 4-point scale of 0=none to 3=severe. Chi-square and t-test were used to compare the clinical, functional, laboratory and US assessments between the DMARD (N=37) and combination therapy with DMARD and anti-TNF (N=21) groups. A p-value <0.05 was considered statistically significant. RESULTS: Out of 58 patients, 25.9% had remission by US and 74.1% had synovial effusion or hypertrophy or positive power Doppler signal. Non-significant differences in US synovitis between the two groups were found. CONCLUSIONS: Persistent US activity was evident in a high percentage of rheumatoid arthritis patients in clinical remission by DAS28. No differences in subclinical synovitis measured by US were found between patients with DMARD and anti-TNF-induced clinical remission.

Algorithm for identification of undifferentiated peripheral inflammatory arthritis: a multinational collaboration through the 3e initiative.

OBJECTIVE: To develop an algorithm for identification of undifferentiated peripheral inflammatory arthritis (UPIA). METHODS: An algorithm for identification of UPIA was developed by consensus during a roundtable meeting with an expert panel. It was informed by systematic reviews of the literature used to generate 10 recommendations for the investigation and followup of UPIA through the 3e initiative. The final recommendations from the 3e UPIA Initiative were made available to the panel to guide development of the algorithm. The algorithm drew on the clinical experience of the consensus panel and evidence from the literature where available. RESULTS: In patients presenting with joint swelling a thorough evaluation is required prior to diagnosing UPIA. After excluding trauma, the differential diagnosis should be formulated based on history and physical examination. A minimum set of investigations is suggested for all patients, with additional ones dependent on the most probable differential diagnoses. The diagnosis of UPIA can be made if, following these evaluations, a more specific diagnosis is not reached. Once a diagnosis of UPIA is established, patients should be closely followed as they may progress to a specific diagnosis, remit, or persist as UPIA, and additional investigations may be required over time. CONCLUSION: Our algorithm presents a diagnostic approach to identifying UPIA in patients presenting with joint swelling, incorporating the dynamic nature of the condition with the potential to evolve over time.

The swollen joint, the thickened artery, and the smoking gun: tobacco exposure, citrullination and rheumatoid arthritis.

Autoimmune diseases result from an interplay between susceptibility genes and environmental factors. These interacting etiopathogenetic components converge in a critical step preceding disease, the loss of tolerance to self. In this review, we examine the evidences linking tobacco smoking with the initiation and perpetuation of inflammation affecting both the synovial membrane and the endothelial lining in patients with rheumatoid arthritis. This disease is a compelling argument for the decisive role of environment in the triggering of a human autoimmune disease in genetically prone individuals.

Leucemia aguda en niños con diagnóstico erróneo de artritis idiopática juvenil / Acute leukemia in children erroneously diagnosed as idiopathic juvenile arthritis

Se presentan 3 niños venezolanos con leucemia aguda cuya enfermedad se inició con dolor e inflamación articular, inicialmente se les diagnosticó artritis idiopática juvenil. El cuadro clínico se caracterizó por artritis migratoria de grandes articulaciones, dolor óseo metafisario de predominio nocturno, aumento de los reactantes de fase aguda desproporcionado para el número de articulaciones afectadas y elevación de la lactatodeshidrogenasa. Un paciente presentó dolor sacroilíaco persistente que condujo al diagnóstico incorrecto de espondiloartritis. Los hallazgos radiológicos predominantes fueron osteopenia, osteólisis y presencia de bandas radiotransparentes metafisarias. Esta combinación de manifestaciones clínicas, hallazgos de laboratorio y cambios radiológicos debe hacer sospechar una enfermedad mieloproliferativa en niños con inflamación articular (AU)

We here present 3 Venezuelan children with acute leukemia, initially diagnosed as idiopathic juvenile arthritis because of the occurrence of pain and joint swelling at the onset of disease. Joint pain was aggravated at night and the arthritis showed a migratory pattern, mainly affecting large joints in an asymmetrical fashion. One patient presented with persistent unilateral sacroiliac pain leading to a wrong diagnosis of spondyloarthritis. The elevation of acute phase reactants, disproportionate to the extent of joint disease, and marked elevation of serum lactate dehydrogenase, as well as characteristic radiological changes allowed the correct diagnosis in all cases. This combination of clinical manifestations, clinical laboratory findings, and joint and bone imaging should prompt the clinician to an early diagnosis of acute leukemia in children with arthritis (AU)

[Acute leukemia in children erroneously diagnosed as idiopathic juvenile arthritis]. / Leucemia aguda en niños con diagnóstico erróneo de artritis idiopática juvenil.

We here present 3 Venezuelan children with acute leukemia, initially diagnosed as idiopathic juvenile arthritis because of the occurrence of pain and joint swelling at the onset of disease. Joint pain was aggravated at night and the arthritis showed a migratory pattern, mainly affecting large joints in an asymmetrical fashion. One patient presented with persistent unilateral sacroiliac pain leading to a wrong diagnosis of spondyloarthritis. The elevation of acute phase reactants, disproportionate to the extent of joint disease, and marked elevation of serum lactate dehydrogenase, as well as characteristicradiological changes allowed the correct diagnosis in all cases. This combination of clinical manifestations, clinical laboratory findings, and joint and bone imaging should prompt the clinician to an early diagnosis of acute leukemia in children with arthritis.