Sobrevida, eficacia y seguridad de Golimumab en pacientes con Artritis Reumatoidea y Espondiloartritis: Datos de una cohorte argentina / Survival, efficacy and safety of Golimumab in patients with Rheumatoid Arthritis and Spondyloarthritis: Data from an Argentine cohort

Objetivos: Golimumab ha sido aprobado para el tratamiento de pacientes con artritis reumatoidea (AR), artritis psoriásica (APs) y espondiloartritis axial. Sin embargo, los datos provenientes de nuestra región son escasos. El objetivo de este estudio fue evaluar la eficacia, seguridad y sobrevida acumulada de golimumab en pacientes de la vida real con AR, APs y espondilitis anquilosante (EA) de diferentes centros de Argentina. Material y métodos: Se llevó a cabo un estudio longitudinal, en el que se incluyeron pacientes consecutivos mayores de 18 años con diagnóstico de AR (criterios ACR/EULAR 2010), APs (criterios CASPAR) y Espax (criterios ASAS 2009), que hayan iniciado tratamiento con golimumab de acuerdo a la indicación médica. Se obtuvieron los datos por revisión de historias clínicas. Se consignaron características sociodemográficas, clínicas, comorbilidades y tratamientos previos. Con respecto al golimumab, se registraron fecha de inicio, vía de administración y tratamientos concomitantes. Se determinó la actividad de la enfermedad mediante DAS28 en el caso de la AR, por DAPSA y MDA para APs y por BASDAI en el caso de Espax. Se consignó la presencia de eventos adversos (EA). En el caso de suspensión del tratamiento, se identificaron la fecha y motivo del mismo. Los pacientes fueron seguidos hasta la suspensión del golimumab, pérdida de seguimiento, muerte, o finalización del estudio (30 de noviembre de 2020). Resultados: Se incluyeron 182 pacientes, 116 con diagnóstico de AR, 30 con APs y 36 con Espax. La mayoría de ellos (70.9%) eran mujeres con una edad mediana (m) de 55 años (RIC 43.8-64) y una duración de la enfermedad m de 7 años (RIC 4-12.7) al inicio del tratamiento. El 34.6% de los mismos habían recibido al menos una droga modificadora de la enfermedad (DME) biológica (-b) o sintética dirigida (-sd) previamente. El seguimiento total fue de 318.1 pacientes/año. El tratamiento con golimumab mostró mejoría clínica en los tres grupos de pacientes. La incidencia de eventos adversos fue de 6.6 por 100 pacientes/año, siendo las infecciones las más frecuentes. Durante el seguimiento, 50 pacientes (27.5%) suspendieron golimumab, la causa más frecuente fue el fracaso del tratamiento (68%), seguida de la falta de cobertura (16%) y el desarrollo de eventos adversos (10%). La persistencia de golimumab fue del 76% y 68% a los 12 y 24 meses, respectivamente. Se registró una sobrevida de 50.2 meses (IC 95% 44.4-55.9). Los pacientes que habían recibido tratamiento previo con DME-b y/o -sd mostraron una menor sobrevida (HR 2.4, IC 95% 1.3-4.4). Conclusiones: El tratamiento con golimumab en pacientes de la vida real en Argentina ha demostrado una buena eficacia y seguridad. La sobrevida del fármaco fue de más de 4 años y casi el 80% seguía usando golimumab después de un año. El tratamiento previo con otros DME-b o -sd se asoció con una menor sobrevida al tratamiento.

Objectives: Golimumab is approved for patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondyloarthritis. However, data from our region are scarce. The aim of this study was to evaluate the efficacy, safety, and cumulative survival of golimumab in real-life patients with RA, PsA and axial spondyloarthritis (axSpa) from different rheumatology centers in Argentina. Material and methods: We performed a longitudinal study of consecutive adults with RA (ACR/EULAR 2010 criteria), PsA (CASPAR criteria) and axSpa (ASAS 2009 criteria), who have started treatment with golimumab according to medical indication. Data was obtained by review of medical records. Sociodemographic and clinical data, musculoskeletal manifestations, comorbidities and previous treatments were recorded. In reference to golimumab treatment, start date, route of administration and concomitant treatments were identified. Disease activity was assessed using DAS28 for RA patients, DAPSA and MDA for PsA and BASDAI for axSpa. The presence of adverse events was recorded. If golimumab was stopped, date and cause was documented. Patients were followed up until golimumab discontinuation, loss of follow-up, death, or study completion (November 30, 2020). Results: In total 182 patients were included, 116 with a diagnosis of RA, 30 with PsA and 36 with axSpa. Most of them (70.9%) were female with a median (m) age of 55 years (IQR 43.8-64) and m disease duration of 7 years (IQR 4-12.7) at treatment initiation. Al least one prior biological (-b) and/or targeted synthetic (-ts) disease modifying antirheumatic drug (DMARD) was received by 63 patients (34.6%). Total follow-up was 318.1 patients/year. Golimumab treatment showed clinical improvement in all three groups of patients. The incidence of AE was 6.6 per 100 patients/year, being infections the most frequents ones. During follow-up, 50 patients (27.5%) discontinued golimumab, the most frequent cause was treatment failure (68%), followed by lack of health insurance (16%) and adverse events (10%). Golimumab persistence was 76% and 68% at 12 and 24 months, respectively. Treatment survival was 50.2 months (95% CI 44.4-55.9). Patients who had received prior treatment with b- or ts-DMARDs showed lower survival (HR 2.41, 95% CI 1.3-4.4). Conclusions: Golimumab treatment in real life patients in Argentina has shown good efficacy and safety. Drug survival was over 4 years and almost 80% were still using golimumab after one year. Prior treatment with other b- or ts-DMARDs was associated with lower treatment survival.

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.

Performance of Ultrasonography Compared to Conventional Radiography for the Diagnosis of Osteoarthritis in Patients With Knee Pain.

Purpose: To investigate the performance of ultrasonography (US) for the detection of knee osteoarthritis (OA) in patients suffering from knee pain, compared to conventional radiographs. Methods: Cross-sectional study performed at a university teaching hospital. Consecutive patients complaining of unilateral or bilateral mechanical knee pain who signed an informed consent were included. All patients underwent simultaneously an ultrasonographic and a radiographic evaluation of the knee. Exclusion criteria were age under 18 years, prior diagnosis of knee OA, diagnosis of inflammatory arthritis, history of knee surgery or trauma, severe knee deformities, and corticosteroid injection within the last 2 months. The diagnostic properties of US for the detection of knee OA were evaluated using radiological data as the reference method. Evaluated test properties were sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and the positive and negative likelihood ratio (LR+ and LR-). Results: Three-hundred twenty-two knees (281 patients) were included. Radiographic degenerative changes were present in 56.8% (183) of the evaluated knees. Regarding the diagnostic properties of the US, the presence of either osteophytes or the compromise of the femoral hyaline cartilage had the best sensitivity to detect OA (95%), with a NPV of 92% and a LR- of 0,07, while the combined identification of osteophytes and compromise of the femoral hyaline cartilage had the best specificity (94%), with 94% PPV and a LR+ of 13. Conclusion: US demonstrated an excellent sensitivity with an adequate specificity for the detection of radiographic knee OA.

Incidence of cancer in a cohort of patients with primary Sjögren syndrome in Argentina.

Primary Sjögren syndrome (pSS) is usually a mild disease, but serious complications such as non-Hodgkin lymphoma-and hypothetically other malignancies-may develop. The aim of this study was to evaluate both overall and specific incidence of cancer in a cohort of patients with pSS compared to the expected incidence in general population of Argentina. Retrospective analytic study of pSS patients fulfilling American-European Consensus Group (AECG) criteria, followed from the time of their diagnosis until the end of the study, death, loss of follow- up, or being given a diagnosis of cancer. Cancer incidence for the general population was obtained from GLOBOCAN 2018, and demographic information was obtained from the national institute for statistics and census. Age- and sex-specific Standardized Incidence Ratio (SIR) were then calculated. One hundred fifty-seven patients, with a mean age of 57.8 years (SD 18.3), were included. Mean patient follow-up duration was 7.37 years (SD 4.2), contributing to a total of 1158 patient/years. Fifteen patients developed a malignancy during follow-up. Cancer incidence for pSS patients was compared with the general population's incidence through SIRs. Female patient's SIRs for overall cancer was 4.17 (95% CI 2.30-6.87), non-Hodgkin lymphoma 41.40 (95% CI 10.12-102.1), multiple myeloma 41.49 (95% CI 1.14-167.28), tongue cancer 44.4 (95% CI 1.23-177.31), uterus cancer 8.39 (95% CI 0.19-40.73), lung cancer 4.51 (95% CI 0.1-22.16), and breast cancer 3.76 (95% CI 1.04-9.45). An increased overall cancer risk, and particularly for non-Hodgkin lymphoma, multiple myeloma, breast cancer and tongue cancer was observed in female pSS patients compared to control group.

Clinical description of patients with cytoplasmic discrete dots pattern (lysosome) on indirect immunofluorescence on HEp-2 cells.

The cytoplasmic discrete dot (CDD) pattern is an unusual finding in indirect immunofluorescence, and its clinical value is unknown. To describe the clinical characteristics of patients with CDD pattern on indirect immunofluorescence (IIF) from our laboratory database and to evaluate possible associations with other autoantibodies and autoimmune diseases. This is a retrospective descriptive study. We included all patients with CDD pattern on IIF in HEp-2 cells with a titer equal or greater than 1/80, using a database of all IIF performed in a reference immunology and rheumatology laboratory between 2007 and 2015. Data on demographics, past medical history, and relevant laboratory findings were recorded and analyzed. We performed 13.056 IIF on HEp-2 cells tests between January 1, 2007 and December 31, 2015, with 6075 positive results. Among them, 5447 had nuclear pattern, 55 had both nuclear and cytoplasmic pattern, and 573 had cytoplasmic pattern. Only 21 showed a CDD pattern. Four patients were excluded since they did not have medical records at the institution. The prevalence of the CDD pattern in our laboratory was 0.35%. The median age was of 62.3 years (SD 9.16) and 100% were female. Fifty-three percent (9/17) had an autoimmune disease, Hashimoto's thyroiditis (4/9) being the most frequent one. In conclusion, cytoplasmic discrete dot pattern is an uncommon finding and its clinical value is uncertain. However, in our study, 53% of the patients had an autoimmune disease.