Efficacy, Safety, and Pharmacodynamic Effects of the Bruton's Tyrosine Kinase Inhibitor Fenebrutinib (GDC-0853) in Systemic Lupus Erythematosus: Results of a Phase II, Randomized, Double-Blind, Placebo-Controlled Trial.

OBJECTIVE: Fenebrutinib (GDC-0853) is a noncovalent, oral, and highly selective inhibitor of Bruton's tyrosine kinase (BTK). The efficacy, safety, and pharmacodynamics of fenebrutinib in systemic lupus erythematosus (SLE) were assessed in this phase II, multicenter, randomized, placebo-controlled study. METHODS: Patients who had moderately to severely active SLE while receiving background standard therapy were randomized to receive placebo, fenebrutinib 150 mg once daily, or fenebrutinib 200 mg twice daily. Glucocorticoid taper was recommended from weeks 0 to 12 and from weeks 24 to 36. The primary end point was the SLE Responder Index 4 (SRI-4) response at week 48. RESULTS: Patients (n = 260) were enrolled from 44 sites in 12 countries, with the majority from Latin America, the US, and Western Europe. The SRI-4 response rates at week 48 were 51% for fenebrutinib 150 mg once daily (P = 0.37 versus placebo), 52% for fenebrutinib 200 mg twice daily (P = 0.34 versus placebo), and 44% for placebo. British Isles Lupus Assessment Group-based Combined Lupus Assessment response rates at week 48 were 53% for fenebrutinib 150 mg once daily (P = 0.086 versus placebo), 42% for fenebrutinib 200 mg twice daily (P = 0.879 versus placebo), and 41% for placebo. Safety results were similar across all arms, although serious adverse events were more frequent with fenebrutinib 200 mg twice daily. By week 48, patients treated with fenebrutinib had reduced levels of a BTK-dependent plasmablast RNA signature, anti-double-stranded DNA autoantibodies, total IgG, and IgM, as well as increased complement C4 levels, all relative to placebo. CONCLUSION: While fenebrutinib had an acceptable safety profile, the primary end point, SRI-4 response, was not met despite evidence of strong pathway inhibition.

Chronic Joint Pain 3 Years after Chikungunya Virus Infection Largely Characterized by Relapsing-remitting Symptoms.

OBJECTIVE: To determine the frequency of chronic joint pain and stiffness 3 years after infection with chikungunya virus (CHIKV) in a Latin American cohort. METHODS: A cross-sectional followup of 120 patients from an initial cohort of 500 patients who reported joint pain 2 years after infection from the Atlántico Department, Colombia. Patients were clinically diagnosed as having CHIKV during the 2014-2015 epidemic, and baseline and followup symptoms at 40 months were evaluated in serologically confirmed cases. RESULTS: Of the initial 500 patients enrolled in the study, 482 had serologically confirmed chikungunya infection. From this group, 123 patients reported joint pain 20 months after infection, and 54% of those patients reported continued joint pain 40 months after infection. Therefore, 1 out of every 8 people who tested serologically positive for CHIKV infection had persistent joint pain 3 years after infection. Participants who followed up in person were predominantly adult (mean ± SD age 51 ± 14 yrs) and female (86%). The most common type of pain reported in these patients at 40 months post-infection was pain with periods of relief and subsequent reoccurrence, and over 75% reported stiffness after immobility, with 39% experiencing morning stiffness. CONCLUSION: To our knowledge, this is the first report to describe persistent joint pain and stiffness 40 months after viral infection. The high frequency of chronic disease highlights the need to develop prevention and treatment methods. Further studies should be conducted to understand the similarities between post-chikungunya joint pain and rheumatoid arthritis.

II Consenso Colombiano para el Manejo de la Osteoporosis Posmenopáusica / Second Colombian Consensus on the Management of Post-menopausal Osteoporosis: 2017 Update

Resumen La Asociación Colombiana de Osteoporosis y Metabolismo Mineral se reunió a principios de 2017 para actualizar el Consenso Colombiano de Osteoporosis, elaborado por primera vez en 2005, un paso que se consideró necesario en vista del subdiagnóstico de esta enfermedad, el impacto esperado del envejecimiento poblacional y los cambios en el tratamiento farmacológico que ha habido desde entonces. Se seleccionó un equipo técnico con especialistas de múltiples áreas y amplia trayectoria, repartidos en 4 grupos de trabajo: definición y epidemiología, diagnóstico, tratamiento farmacológico y medidas no farmacológicas. Luego de una revisión de la literatura científica, en reuniones de trabajo se generaron las definiciones y recomendaciones que se resumen en este documento.

Abstract The Colombian Osteoporosis and Mineral Metabolism Association met in early 2017 to update the Colombian Consensus on Osteoporosis. This was first issued in 2005, and is seen as a necessary step in view of the underdiagnosed status of this disease, and the expected impact of population ageing. A technical team was formed with specialists with long experience across multiple disciplines, who were assigned to four working groups: definitions and epidemiology, diagnosis, pharmacological treatment, and non-pharmacological treatment. After a scientific literature review and a series of meetings, the definitions and recommendations are summarised in this article.

Romosozumab FRAME Study: A Post Hoc Analysis of the Role of Regional Background Fracture Risk on Nonvertebral Fracture Outcome.

In the pivotal Fracture Study in Postmenopausal Women with Osteoporosis (FRAME; NCT01575834), 1 year of the bone-forming agent romosozumab significantly reduced new vertebral and clinical fracture risk versus placebo. Nonvertebral fracture risk was not significantly reduced in the overall population, influenced by a low placebo-group fracture rate, observed particularly in the highest-enrolling region of Latin America. In year 1 of FRAME, postmenopausal women with a T-score of -2.5 to -3.5 at the total hip or femoral neck were randomized to subcutaneous romosozumab 210 mg or placebo once monthly for 12 months. Of 7180 randomized women, 43% were from Latin America, largely Colombia and Brazil. Prespecified analyses assessed fracture risk reductions by geographic regions. A significant treatment-by-geographic region interaction for the clinical (p = 0.029) and nonvertebral fracture (p = 0.042) endpoints led to further characterization of the Latin American population and comparison with the remaining study population, grouped post hoc as rest-of-world. Nonvertebral fracture efficacy in the overall population was also assessed by baseline fracture risk using the Fracture Risk Assessment Tool (FRAX). Romosozumab significantly and consistently reduced new vertebral fracture risk in Latin America (70% reduction; p = 0.014) and rest-of-world (74% reduction; p < 0.001). For nonvertebral fracture, risk reductions were observed in rest-of-world (42% reduction; p = 0.012), with no treatment effect observed in Latin America, where background nonvertebral fracture risk was low (1.2% in the placebo group). Consistent with this finding, in the overall population, greater reductions in nonvertebral fracture risk were observed among women with higher FRAX scores. These findings suggest that fracture risk assessment should consider regional factors in addition to classical risk factors, such as bone mineral density. In women at high risk for fracture, romosozumab reduced nonvertebral fracture risk within 1 year. © 2018 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals, Inc.

Fracturas vertebrales morfométricas y su relación con 25 OH vitamina D, índice de masa corporal y edad en mujeres seniles / Morphometric vertebral fractures and their relationship with 25 OH-vitamin D, body mass index, and age in elderly women

Objetivo: Determinar la presencia de fracturas vertebrales morfométricas y su relación con 25 OH vitamina D, índice de masa corporal y edad en mujeres seniles. Materiales y métodos: Estudio transversal. Se analizaron 319 mujeres seniles, provenientes del estudio "Salud osteomuscular del anciano". La determinación de fracturas vertebrales morfométricas se realizó de manera radiográfica, en tanto que los niveles de 25 OH vitamina D se midieron por inmunoanálisis por quimioluminiscencia (CLIA) Liaison* 25 OH vitamina D Total Assay Ref 310600, utilizando el equipo Diasorin Liaison* Analyzer. El índice de masa corporal se obtuvo, según las recomendaciones de la Organización Mundial de la Salud, como el peso en kilogramos sobre la talla en metros al cuadrado; la edad fue verificada con el documento de identidad y el ingreso del mismo a las bases de datos nacionales (SISPRO-FOSYGA). Resultados: El promedio de edad fue de 74,3 arios (DE ± 7,2). La prevalencia global de fracturas fue de 17,9%; así mismo, el 54,9% de las participantes tenía valores entre 20 y 29ng/ml de 25 OH vitamina D y el 58,9% tenía valores de índice de masa corporal inferior a 25 kg/m². El promedio de 25 OH vitamina D fue inferior en las participantes fracturadas (19,7 vs. 25,1) (p<0,05); el índice de masa corporal también fue menor en las fracturadas (23,5 vs. 24,6) (p>0,05), pero la edad fue mayor: 78,9 vs. 73,4 (p<0,05). Al comparar los promedios de 25 OH vitamina D en participantes fracturadas y no fracturadas, se encontraron niveles significativamente menores de 25 OH vitamina D en las participantes con fractura mayores de 69 años, y al considerar el índice de masa corporal, los valores de 25 OH vitamina D fueron significativamente inferiores en cada una de las categorías de las participantes con fractura. Conclusión: Se encontró una relación estadísticamente significativa entre poseer fracturas vertebrales morfométricas y tener: 1) niveles bajos de 25 OH vitamina D, 2) mayor edad, y 3) menor índice de masa corporal.

Objective: To determine the presence of morphometric vertebral fractures, as well as their relationship with 25 OH vitamin D, body mass index, and age in elderly women. Materials and methods: A cross-sectional study was conducted on 319 elderly women from the study 'Musculoskeletal Health in the Elderly'. The morphometric determination of vertebral fractures was performed with radiography, while the levels of 25 OH vitamin D were determined by the chemiluminescent immunoassay (CLIA) method using the Liaison® 25 OH Vitamin D Total Assay 25 (Ref 310 600), using the Liaison® Analyser. The body mass index was obtained as recommended by the World Health Organisation; weight in kilograms over height in metres squared. The age of the participants was verified by their identity card, and their income details from the national data bases (SISPRO-FOSYGA). Results: The mean age was 74.3 years (SD ± 7.2). The overall prevalence of fractures was 17.9%; 54.9% of participants had values between 20 and 29ng/ml 25 OH vitamin D, and 58.9% had body mass index values less than 25 kg/m². The mean 25 OH vitamin D was lower in participants with fractures (19.7 vs. 25.1) (P < .05). Body mass index was also lower in those with fractures (23.5 vs. 24.6) (P < .05), but age was higher: 78.9 vs. 73.4 (P < .05). When comparing the mean levels of 25 OH vitamin D in fractured and non-fractured participants, significantly lower levels of 25 OH vitamin D were found in participants with fractures over 69 years-old, and on comparing the body mass index, the values of 25 OH vitamin D were significantly lower in each of the categories of participants with a fracture. Conclusion: A statistically significant relationship was found between morphometric vertebral fractures and: 1) low levels of 25 OH vitamin D, 2) being older and, and 3) a lower body mass index.

Caracterización clínica de sujetos infectados con virus chikungunya, en una población del Caribe colombiano / Clinical profile of patients infected with the chikungunya virus in a Colombian Caribbean population

OBJETIVO: Caracterizar clínicamente una población infectada con el virus chikungunya. MATERIALES Y MÉTODOS: Estudio descriptivo longitudinal, prospectivo con 109 pacientes remitidos a consulta externa o urgencia, de la Fundación Hospital Universitario Metropolitano de Barranquilla, para realizar confirmación serológica, previo diagnóstico clínico de infección por virus chikungunya, por reumatólogos del Centro de Reumatología y Ortopedia. Los pacientes con diagnóstico confirmado serológicamente se sometieron a pruebas inmunológicas para diagnóstico diferencial con artritis reumatoide. RESULTADOS: Se realizó diagnóstico serológico por ELISA para virus chikungunya anti-IgG y anti-IgM; ninguno resultó positivo para anticuerpo antichikungunya tipo IgM, mientras que 109 fueron positivos para anticuerpo antichikungunya tipo IgG. El rango de edad fue de 22 a 82 años. Las principales manifestaciones clínicas fueron: 1. dolor localizado: manos: 82%, tobillos con afectación articular: 82%, pies: 72%, cabeza: 69%, espalda: 61%, codos: 57%. 2. Dolor en distintas articulaciones: 76%, músculos: 72%. 3. Edema: región periarticular: 55%, 4. Otra sintomatología de interés clínico: manifestaciones cutáneas: 53%, fiebre: 89%, rash: 5%, náuseas: 31% e incapacidad laboral: 19%.CONCLUSIONES: Los signos y síntomas presentados por los sujetos con chikungunya tienen un amplio componente reumatológico. El compromiso articular en las fases agudas y subagudas semeja el comportamiento de la artritis reumatoide, más no así el compromiso en la fase crónica. No hubo reacción autoinmunitaria y por tanto no se puede clasificar como proceso de tipo artritis reumatoide

OBJECTIVE: To determine the clinical profile of patients infected with the chikungunya virus. MATERIALS AND METHODS: Descriptive longitudinal, prospective study on 109 individuals referred to the outpatient or emergency department of the Fundación Hospital Universitario Metropolitano de Barranquilla for serological confirmation, after being previously diagnosed with chikungunya virus infection by rheumatologists from the Rheumatology and Orthopaedics Centre. Patients with serologically confirmed diagnosis underwent immunological test for differential diagnosis with rheumatoid arthritis. RESULTS: ELISA test were performed to serologically diagnose chikungunya virus, IgG and IgM antibodies. No chikungunya IgM test was positive, while 109 were positive for chikungunya IgG antibody. The age range was 22 to 82 years. The main clinical manifestations were: 1. localised pain in the hands: 82%, ankles joints: 82%, feet: 72%, headache 69%, back: 61%, and elbow: 57%.2. Pain in other joints: 76%, and muscles 72%.3. Peri-articular swelling: 55%.4. Other symptoms of clinical interest: cutaneous manifestations: 53%, fever 89%, rash: 5%, nausea 31%, and incapacity: 19%. CONCLUSIONS: Most signs and symptoms presented by patients with chikungunya have an extensive rheumatological component that merits further study. The joint compromise in acute and subacute phase resembles the behaviour of rheumatoid arthritis, but not so similarly in the chronic phase. There was no autoimmune reaction, and therefore can not be classified as a type of Rheumatoid process

Immunological response of a population from the Caribbean region of Colombia infected with the chikungunya virus / Respuesta inmunitaria de una población del Caribe colombiano infectada con el virus chikungunya

INTRODUCTION: Chikungunya virus infection has become a public health problem, due to its immediate effect on the health and quality of life of patients and their families, as well as complications in the medium and long term. Its necessary to determine immunological characteristics of this afection as an important step for the future development of strategies to reduce its incidence and aggressiveness. OBJECTIVE: To characterize immunologically a population from Colombian Caribbean with serologic and clinic diagnosis of chikungunya virus infection. MATERIALS AND METHODS: A descriptive, longitudinal, and prospective study was conducted on in 109 patients with a clinical diagnosis and serological confirmation of chikungunya virus infection and attended in the emergency department of the Fundación Hospital Universitario Metropolitano and the Orthopaedic and Rheumatology Centre. Immunoglobulin G or M type antibodies against Chikungunya virus were determined in a peripheral blood sample using immuno-enzymatic serological and immunological test in order to diagnose rheumatic diseases. RESULTS: Tests were positive for immunoglobulin G type antibodies against chikungunya virus in all of the 109 patients. The results for anti-cyclic citrullinated peptide antibodies, rheumatoid factor, antinuclear, and anti-DNA antibodies were negative in almost all of the 109 patients. CONCLUSIONS: Patients were not in a viral replication process that characterizes the acute phase of the disease. There were no positive results in laboratory test related to rheumatic diseases. High concentrations of certain pro-inflammatory interleukins were found in patients, and the clinical manifestations in these, suggest an inflammatory joint process with severe arthralgia that can mimic the symptoms of a rheumatic disease.

INTRODUCCIÓN: La infección por el virus chikungunya se ha convertido en un problema de salud pública, tanto por su afección inmediata sobre la salud y calidad de vida de los pacientes y sus familias, como por las complicaciones a medio y largo plazos. Es necesario llevar a cabo la caracterización inmunológica de esta afección, como paso importante para el futuro desarrollo de estrategias tendentes a disminuir su incidencia y agresividad. OBJETIVO: Caracterizar inmunológicamente una población del Caribe colombiano con diagnóstico clínico y serológico de infección por el virus chikungunya. MATERIALES Y MÉTODOS: Estudio descriptivo, longitudinal, prospectivo, en 109 pacientes con diagnóstico clínico y confirmación serológica de infección por el virus chikungunya, atendidos en el Servicio de Emergencias de la Fundación Hospital Universitario Metropolitano y en la consulta externa del Centro de Reumatología y Ortopedia. A partir de la toma de muestra de sangre periférica, se determinaron anticuerpos tipo inmunoglobulina G o M contra el virus chikungunya, por ensayo inmunoenzimático y pruebas de serología inmunológicas, orientadas al diagnóstico de enfermedades reumatológicas. RESULTADOS: Se obtuvieron resultados positivos para anticuerpos tipo inmunoglobulina G contra el virus chikungunya en 109 pacientes. Los resultados para anticuerpos antipéptido cíclico citrulinado, factor reumatoide, anticuerpos antinucleares, anticuerpo anti-ADN, fueron negativos en la mayoría de los sujetos. CONCLUSIÓN: Los pacientes no se encontraban en un proceso de replicación viral, característico de la fase aguda de la enfermedad. No hubo resultados positivos en las pruebas de laboratorio relacionadas con enfermedades reumatológicas. Las concentraciones altas halladas son sugerentes de un proceso inflamatorio articular con artralgias severas, que puede mimetizar las condiciones de una enfermedad reumatológica.

Two-year Efficacy and Safety of Etanercept in Pediatric Patients with Extended Oligoarthritis, Enthesitis-related Arthritis, or Psoriatic Arthritis.

OBJECTIVE: The main objective was to determine the 2-year clinical benefit and safety of etanercept (ETN) in children with the juvenile idiopathic arthritis (JIA) categories of extended oligoarthritis (eoJIA), enthesitis-related arthritis (ERA), or psoriatic arthritis (PsA). METHODS: CLIPPER was a 96-week, phase IIIb, open-label, multicenter study. Patients with eoJIA, ERA, or PsA received ETN 0.8 mg/kg once weekly (50 mg max) for up to 96 weeks. The proportions of patients reaching the JIA American College of Rheumatology (ACR) 30/50/70/90/100 and inactive disease responses at Week 96 were calculated. Adverse events (AE) were collected throughout the study (intention-to-treat sample). RESULTS: There were 127 patients (eoJIA n = 60, ERA n = 38, PsA n = 29) who received ≥ 1 dose of ETN. The mean disease duration was 31.6 (eoJIA), 23.0 (ERA), and 21.8 (PsA) months. At Week 96, JIA ACR 30/50/70/90/100/inactive disease responses (95% CI) were achieved by 84.3% (76.7, 90.1), 83.5% (75.8, 89.5), 78.7% (70.6, 85.5), 55.1% (46.0, 63.9), 45.7% (36.8, 54.7), and 27.6% (20.0, 36.2) of patients, respectively. The most common AE (no. events, events per 100 patient-yrs) overall were headache (23, 10.7), pyrexia (12, 5.6), and diarrhea (10, 4.6). The most common infections were upper respiratory tract infection (83, 38.6), pharyngitis (50, 23.2), gastroenteritis (22, 10.2), bronchitis (19, 8.8), and rhinitis (17, 7.9). No cases of malignancy, active tuberculosis, demyelinating disorders, or death were reported. CONCLUSION: Over 96 weeks of therapy, ETN demonstrated sustained efficacy at treating the clinical symptoms of all 3 JIA categories, with no major safety issues.

Fracture risk assessment in Latin America: is Frax an adaptable instrument for the region?

Osteoporosis is a generalized disease of bone that increases fracture risk. Multiple factors influence this risk, besides low bone mass. To decrease osteoporotic fractures, those patients who require preventive management should be readily identified. This paper aims to review current information on the use of the fracture risk assessment tool (FRAX) in Latin America. Bone mineral density measurement is currently the method of reference for evaluating the fracture risk and opting for treatment; but, it misses a notable proportion of individuals who have clinical risk factors for osteoporosis and fractures. FRAX was designed to predict the 10-year absolute risk of sustaining a major osteoporotic fracture or a hip fracture. Although data is available for several countries, from Latin America, only Argentina appears in the current version of the tool. Its present use in other Latin American countries is possible with some adaptations based in similarities of epidemiological information of each country with some of the existing databases. The cutoff value beyond which treatment should be initiated needs to be determined, based not only on clinical criteria, but also on economic considerations.