Effect of Tocilizumab on LDL and HDL Characteristics in Patients with Rheumatoid Arthritis. An Observational Study.

BACKGROUND: In patients with rheumatoid arthritis (RA), qualitative alterations of low and high-density lipoproteins (LDL and HDL, respectively) might partially explain their increased cardiovascular risk. Tocilizumab has been associated with an increase in lipids, including triglyceride (TG) and cholesterol levels. The aim of this study is to evaluate the effect of tocilizumab on certain LDL and HDL characteristics (oxidized LDL levels, HDL-associated enzymes, chemical composition of both total HDL and HDL3c subpopulation, and their capacity to promote cellular cholesterol efflux) at baseline and 3 months after the start of treatment in patients with RA. METHODS: Twenty-eight RA patients (ACR/EULAR 2010 criteria) with indication of treatment with tocilizumab were included in the present study. Clinical assessment [Health assessment questionnaire (HAQ)], disease activity score 28 (DAS28), high-sensitivity C reactive protein (hsCRP) concentration, lipid profile, and lipoprotein (a) [Lp(a)] levels were evaluated in all patients at baseline and after 3 months of treatment with tocilizumab. Lipoprotein characteristics were evaluated through the levels of oxidized LDL (OxLDL), the activity of paraoxonase (PON) 1, the composition of total HDL and small, dense HDL3c subpopulation, and their ability to promote cellular cholesterol efflux. RESULTS: After 3 months of treatment with tocilizumab, HAQ (- 23%, p < 0.05), DAS28 (- 49%, p < 0.001), and hsCRP (- 94%, p < 0.01) levels decreased significantly. Total cholesterol (TC), LDL-C, non-HDL-C, and apo B levels showed a significant increase after treatment (TC: + 7.0%, p < 0.01; LDL-C: + 10%, p < 0.01; non-HDL-C: + 9.9%, p < 0.01; and apo B: + 9.6%, p < 0.05). Decreases in Lp(a) and OxLDL levels were also observed after treatment [Lp(a): - 50%, p < 0.01; and oxLDL: - 5.4%, p < 0.05]. The latter was in accordance with the increment detected in PON activity. No changes were observed in HDL capacity to promote cholesterol efflux (p > 0.05) in the whole group. CONCLUSIONS: Treatment with tocilizumab reduced hsCRP levels and displayed positive effects on certain lipoprotein-related parameters, such as a potent decrease inLp(a) and a reduction in OxLDL levels. Moreover, HDL capacity to promote cellular cholesterol efflux was maintained after 3 months of treatment.

Osteoporotic fractures in rheumatoid arthritis patients in Argentina: a matched retrospective cohort study.

BACKGROUND: To compare the incidence of osteoporotic fractures in patients with rheumatoid arthritis (RA) with matched controls from a university hospital. METHODS: Consecutive RA patients (n = 100) were matched (age and sex) with controls (1:2). The follow-up period began at the index date, defined as the date of diagnosis for RA patients and the date of the first medical claim at the Health Management Organization (HMO) for non-RA patients. Fracture incidence rates per 1000 persons-years (PY) for distinct types of fractures were calculated. Multivariate cox regression analysis was performed to identify factors associated with fractures. RESULTS: One hundred RA patients were followed for a total of 975.1 patients-years and 200 controls for 1485.7 patients-years. No difference was found in the overall fracture incidence rate per 1000 PY between RA and controls (19.5, 95% CI 12.7-28.6 vs 12.1, 95% CI 7.7-18.7, p = 0.07). In the Cox regression analysis, only age (HR 1.06, 95% CI 1.02-1.11, p = 0.006) and history of a prior fracture (HR 9.85, 95% CI 2.97-32.64, p <  0.001) were associated with fractures after the index date. The stratified analysis of the fractures by location showed that only the vertebral fractures were more frequent in RA patients compared with controls (12.9 per 1000 PY, 95% CI 8.9-25.8, vs. 3.4, 95% CI 1.4-8.1, respectively, p = 0.01). CONCLUSION: Patients with RA didn't show an overall increased risk of osteoporotic fractures compared with matched controls, but vertebral fractures were more frequently observed in patients with RA.

Osteoporotic fractures in rheumatoid arthritis patients in Argentina: a matched retrospective cohort study

Abstract Background: To compare the incidence of osteoporotic fractures in patients with rheumatoid arthritis (RA) with matched controls from a university hospital. Methods: Consecutive RA patients (n = 100) were matched (age and sex) with controls (1:2). The follow-up period began at the index date, defined as the date of diagnosis for RA patients and the date of the first medical claim at the Health Management Organization (HMO) for non-RA patients. Fracture incidence rates per 1000 persons-years (PY) for distinct types of fractures were calculated. Multivariate cox regression analysis was performed to identify factors associated with fractures. Results: One hundred RA patients were followed for a total of 975.1 patients-years and 200 controls for 1485.7 patients-years. No difference was found in the overall fracture incidence rate per 1000 PY between RA and controls (19.5, 95% CI 12.7-28.6 vs 12.1, 95% CI 7.7-18.7, p =0.07). In the Cox regression analysis, only age (HR 1.06, 95% CI 1.02-1.11, p = 0.006) and history of a prior fracture (HR 9.85, 95% CI 2.97-32.64, p < 0.001) were associated with fractures after the index date. The stratified analysis of the fractures by location showed that only the vertebral fractures were more frequent in RA patients compared with controls (12.9 per 1000 PY, 95% CI 8.9-25.8, vs. 3.4, 95% CI 1.4-8.1, respectively, p =0.01). Conclusion: Patients with RA didn't show an overall increased risk of osteoporotic fractures compared with matched controls, but vertebral fractures were more frequently observed in patients with RA.

Fragility fractures in psoriatic arthritis patients: a matched retrospective cohort study.

OBJECTIVE: To compare incidental fragility fractures in psoriatic arthritis (PsA) patients with matched controls from a university hospital. METHODS: Consecutive PsA patients were matched (age and sex) with controls (1:2). Follow-up began at index date, defined as the date of PsA diagnosis for cases and their respective controls, until the last hospital visit, death or the end of the study (31 December 2017). Electronic medical records were reviewed for osteoporotic fractures. Incidence rates per 100,000 persons-years (PY) of distinct types of fractures after index dates were calculated and compared between groups. A multivariate Cox regression analysis was performed to investigate determinants of fractures. RESULTS: Ninety-two PsA patients and 184 controls were included. No difference was found in the overall fracture incidence rate per 100,000 PY between PsA and controls (1020 95% CI 510-1930, vs 870 95% CI 520-1390, p = 0.36). Vertebral fractures were numerically more frequent in PsA patients with an incidence rate of 1020 (95% CI 510-1930) per 100,000 PY versus 460 (95% CI 240-920), per 100,000 PY in the control group but it did not reach statistical significance (p = 0.06). In the Cox regression analysis, after adjusting for bisphosphonate use, only age (HR 1.10, 1.05-1.16, p < 0.001) and female sex (HR 3.94, 1.11-13.91, p = 0.03) were associated with fractures while PsA diagnosis and use of glucocorticoids were not. CONCLUSION: In this cohort of PsA patients, no overall increased risk of fractures was found in comparison with matched controls. Key Points • PsA could have different effects on bone, leading to confusing results in bone densitometry readings contributing to the difficulty in establishing the real prevalence of OP in PsA. • Vertebral fractures were more frequent in PsA patients compared to controls, but it did not reach statistical significance. No difference was found in the overall fracture incidence rate.

Rheumatoid Arthritis Patient's Journey: Delay in Diagnosis and Treatment.

OBJECTIVES: The aims of this study were to establish delay times from articular symptoms onset to first rheumatologist consultation, rheumatoid arthritis (RA) diagnosis, and treatment initiation with disease-modifying antirheumatic drug (DMARD) therapy and to assess the impact of delayed diagnosis on structural damage. METHODS: This was an observational cohort study. Rheumatoid arthritis adult patients treated in a private health system between January 1, 1996, and December 31, 2016, were included. Electronic medical records were reviewed to obtain clinical and demographic data, dates of first disease symptom, diagnosis, and date of first treatment with DMARDs. Physical function (Health Assessment Questionnaire) and structural damage (Sharp score modified by van der Heijde) were also assessed. RESULTS: Two hundred forty-six patients (81% female), with a mean age of 67.25 (standard deviation [SD], 14.53) years, were included. At the end of follow-up period, median Health Assessment Questionnaire (n = 145) and radiological scores (n = 171) were 0.125 (interquartile range, 0-0.87) and 15 (interquartile range, 6-33), respectively. A mean of 9.2 (SD, 20) months (median, 3 months) elapsed from the first disease symptom to rheumatologist consultation, 14.2 (SD, 24) months (median, 4.8 months) to RA diagnosis, and 16.9 (SD, 25.4) months (median, 7 months) to treatment initiation with DMARDs. Significantly greater structural damage was found in patients with a diagnosis delay of more than 12 months (n = 70) (p = 0.0325). CONCLUSIONS: Despite good access to medical consultation in a private health system, there is still a delay to RA diagnosis and to start pharmacological therapy. A delay of more than 12 months was significantly associated with greater radiological damage after 5 years of follow-up.

Incidence and prevalence of granulomatosis with polyangiitis and microscopic polyangiitis in health management organization in Argentina: a 15-year study.

BACKGROUND/OBJECTIVE: Our objective was to estimate incidence and prevalence rates of granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) using data from a university hospital-based health management organization (HIMCO) in Latin America. METHODS: Multiple methods for case finding were used to ensure complete ascertainment. GPA was diagnosed if fulfilling ACR 1990 criteria or a clinical diagnosis was made by an experienced rheumatologist. For MPA, a clinical diagnosis made by an experienced rheumatologist in concordance with Chapel Hill 2012 consensus. Renal limited vasculitis (RLV) ANCA-P positive was considered along with MPA. Global, age-specific, and sex-specific incidence and prevalence rates were calculated for members of the HIMCO with continuous affiliation ≥ 1 year from January 2000 to January 2015. Each person was followed up until GPA or MPA were diagnosed, voluntarily withdraw of the HIMCO, death, or study finalization. Prevalence was calculated on January 1, 2015. RESULTS: Nineteen incident cases of GPA and 28 of MPA were identified from January 2000 to January 2015. During this period, a total of 349,775 HIMCO persons contributed a total of 2,073,438 person-years. GPA and MPA overall incidence rate per 1,000,000 person-years were 9 (95% CI 5-13) and 14 (95% CI 9-19), respectively. Age-specific incidence rates in both female and male patients peaked in the seventh decade of life in our population. On January 1, 2015, prevalence rates were 7.4 per 100,000 (95% CI 2.8-12) for GPA and 5.2 per 100,000 (95% CI 1.3-9) for MPA. Prevalence rates were higher in ages over 70 for both genders and both diseases. CONCLUSION: In this first study from Latin America, incidence and prevalence rates were in ranges of previous reports from other sites of the world. In our population, GPA and MPA were more frequent in women and in older ages, and the incidence of MPA was higher than that of GPA. Key points • In Argentina, MPA incidence was higher than GPA, similar to that reported in other parts of the world. • Prevalence and incidence rates were higher in ages over 70 for both sexes and both diseases.

Daño coronario secundario a enfermedad de Kawasaki / Coronary Lesions in Kawasaki Disease

Introducción: La enfermedad de Kawasaki, una vasculitis aguda de origen desconocido, es actualmente la principal causa de cardiopatía adquirida durante la infancia y sus principales secuelas están relacionadas con las arterias coronarias, por lo que el reconocimiento temprano de la probabilidad de daño coronario posibilita el tratamiento oportuno para disminuir su ocurrencia. Objetivos: Determinar la probabilidad de sufrir daño coronario en pacientes con enfermedad de Kawasaki, reconocer los factores de riesgo para el desarrollo de lesión coronaria y la evolución a largo plazo de estos pacientes. Material y métodos: Se diagnosticó enfermedad de Kawasaki en 245 niños (octubre 1988 - diciembre 2013) con edad media de 3,48 años. Las variables analizadas fueron: edad, sexo, criterios clínicos y de laboratorio de enfermedad de Kawasaki, hallazgos ecocardiográficos y evolución a largo plazo. Se calculó el odds ratio para evaluar las diferentes variables analizadas como probables factores de riesgo de enfermedad coronaria. Resultados: Presentaron daño coronario 39 pacientes: 25 varones y 14 mujeres; edad media: 2,05 años. Se identificaron como factores de riesgo la edad < 3 años, la fiebre prolongada = 6 días, la eritrosedimentación > 50 mm/h, la proteína C reactiva > 100 mg/L y el hematocrito < 30%. Trece pacientes mostraron dilatación transitoria de las arterias coronarias, 12 pacientes aneurismas solitarios de tamaño pequeño o mediano, 7 pacientes aneurismas coronarios múltiples, 6 pacientes aneurismas coronarios gigantes y uno infarto agudo de miocardio por lesión obstructiva grave. La mortalidad hospitalaria fue del 4‰. Conclusiones: La probabilidad de presentar daño coronario en pacientes con enfermedad de Kawasaki fue del 15,91%. Los factores de riesgo para lesión coronaria detectados fueron: edad menor de 3 años, 6 o más días de fiebre, eritrosedimentación > 50 mm/h, proteína C reactiva > 100 mg/L y hematocrito < 30%. En los pacientes con daño coronario residual persistente tratados en forma convencional no hubo eventos adversos durante el seguimiento a mediano y a largo plazos.

Background: Kawasaki disease, a vasculitis of unknown origin, is currently the main cause of acquired heart disease during childhood and its main sequelae are associated with coronary arteries. Therefore, early identification of possible coronary lesions enables adequate treatment to decrease their occurrence. Objectives: The aims of this study were to determine the probability of coronary injury in patients with Kawasaki disease, to identify the risk factors for developing coronary lesions and the long-term outcome of these patients. Methods: A total of 245 children with mean age of 3.48 years were diagnosed with Kawasaki disease between October 1988 and December 2013. Age, sex, clinical and laboratory criteria of Kawasaki disease, echocardiographic findings and long-term outcome were analyzed, and the odds ratio was used to assess their participation as probable risk factors for coronary lesions. Results: Thirty-nine patients presented coronary lesions: 25 male and 14 female patients with mean age of 2.05 years. Risk factors were: age < 3 years; prolonged fever = 6 days, erythrocyte sedimentation rate > 50 mm/hr; C-reactive protein > 100 mg/l and hematocrit < 30%. Thirteen patients showed transient coronary artery dilation, 12 solitary small or medium-sized aneurysms, 7 multiple coronary aneurysms, 6 giant coronary aneurysms and one myocardial infarction by severe obstructive lesion. In-hospital mortality was 4‰. Conclusions: Risk of coronary artery lesions in patients with Kawasaki disease was 15.91%. Risk factors were age under 3 years, fever lasting more than 6 days, erythrocyte sedimentation rate > 50 mm/hr; C-reactive protein > 100 mg/L and hematocrit < 30%. In patients with persistent residual coronary lesions treated conventionally there were no adverse events in the mid- and long-term follow-up.

Daño coronario secundario a enfermedad de Kawasaki / Coronary Lesions in Kawasaki Disease

Introducción: La enfermedad de Kawasaki, una vasculitis aguda de origen desconocido, es actualmente la principal causa de cardiopatía adquirida durante la infancia y sus principales secuelas están relacionadas con las arterias coronarias, por lo que el reconocimiento temprano de la probabilidad de daño coronario posibilita el tratamiento oportuno para disminuir su ocurrencia. Objetivos: Determinar la probabilidad de sufrir daño coronario en pacientes con enfermedad de Kawasaki, reconocer los factores de riesgo para el desarrollo de lesión coronaria y la evolución a largo plazo de estos pacientes. Material y métodos: Se diagnosticó enfermedad de Kawasaki en 245 niños (octubre 1988 - diciembre 2013) con edad media de 3,48 años. Las variables analizadas fueron: edad, sexo, criterios clínicos y de laboratorio de enfermedad de Kawasaki, hallazgos ecocardiográficos y evolución a largo plazo. Se calculó el odds ratio para evaluar las diferentes variables analizadas como probables factores de riesgo de enfermedad coronaria. Resultados: Presentaron daño coronario 39 pacientes: 25 varones y 14 mujeres; edad media: 2,05 años. Se identificaron como factores de riesgo la edad < 3 años, la fiebre prolongada = 6 días, la eritrosedimentación > 50 mm/h, la proteína C reactiva > 100 mg/L y el hematocrito < 30%. Trece pacientes mostraron dilatación transitoria de las arterias coronarias, 12 pacientes aneurismas solitarios de tamaño pequeño o mediano, 7 pacientes aneurismas coronarios múltiples, 6 pacientes aneurismas coronarios gigantes y uno infarto agudo de miocardio por lesión obstructiva grave. La mortalidad hospitalaria fue del 4ë. Conclusiones: La probabilidad de presentar daño coronario en pacientes con enfermedad de Kawasaki fue del 15,91%. Los factores de riesgo para lesión coronaria detectados fueron: edad menor de 3 años, 6 o más días de fiebre, eritrosedimentación > 50 mm/h, proteína C reactiva > 100 mg/L y hematocrito < 30%. En los pacientes con daño coronario residual persistente tratados en forma convencional no hubo eventos adversos durante el seguimiento a mediano y a largo plazos.(AU)

Background: Kawasaki disease, a vasculitis of unknown origin, is currently the main cause of acquired heart disease during childhood and its main sequelae are associated with coronary arteries. Therefore, early identification of possible coronary lesions enables adequate treatment to decrease their occurrence. Objectives: The aims of this study were to determine the probability of coronary injury in patients with Kawasaki disease, to identify the risk factors for developing coronary lesions and the long-term outcome of these patients. Methods: A total of 245 children with mean age of 3.48 years were diagnosed with Kawasaki disease between October 1988 and December 2013. Age, sex, clinical and laboratory criteria of Kawasaki disease, echocardiographic findings and long-term outcome were analyzed, and the odds ratio was used to assess their participation as probable risk factors for coronary lesions. Results: Thirty-nine patients presented coronary lesions: 25 male and 14 female patients with mean age of 2.05 years. Risk factors were: age < 3 years; prolonged fever = 6 days, erythrocyte sedimentation rate > 50 mm/hr; C-reactive protein > 100 mg/l and hematocrit < 30%. Thirteen patients showed transient coronary artery dilation, 12 solitary small or medium-sized aneurysms, 7 multiple coronary aneurysms, 6 giant coronary aneurysms and one myocardial infarction by severe obstructive lesion. In-hospital mortality was 4ë. Conclusions: Risk of coronary artery lesions in patients with Kawasaki disease was 15.91%. Risk factors were age under 3 years, fever lasting more than 6 days, erythrocyte sedimentation rate > 50 mm/hr; C-reactive protein > 100 mg/L and hematocrit < 30%. In patients with persistent residual coronary lesions treated conventionally there were no adverse events in the mid- and long-term follow-up.(AU)