ABSTRACT
INTRODUCTION/OBJECTIVES: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by ongoing inflammation and degradation of synovial joints. The oral JAK inhibitor, upadacitinib, is approved for RA. We conducted an integrated safety analysis of upadacitinib 15 mg once daily (QD) in patients from Latin America (LATAM) versus the rest of the world (RoW). METHODS: Treatment-emergent adverse events (AEs) and laboratory data from six phase 3, randomized controlled trials, adjusted for upadacitinib 15 mg QD use in RA, were analyzed. RESULTS: Overall, 3209 patients received upadacitinib 15 mg QD for 7024 patient-years (PY). LATAM patients (n = 725) had a mean upadacitinib exposure of 1518 PY. Baseline characteristics were generally similar between LATAM and RoW populations. AE rates (including serious/opportunistic infections, tuberculosis, and herpes zoster) and deaths were comparable between populations. LATAM patients had lower serious AE rates per 100 PY (9.4 vs 14.0 E/100 PY) and discontinuation-related AEs (3.9 vs 6.0 E/100 PY) versus RoW. Rates of cardiovascular events were low (≤ 0.5 E/100 PY) and similar between populations. Malignancies, excluding non-melanoma skin cancer, were less common in the LATAM population versus RoW (0.2 vs 1.0 E/100 PY). Laboratory abnormalities were similar between populations, with decreases in hemoglobin, lymphocyte, and neutrophil counts, and elevations in liver enzymes and creatine phosphokinase. Mean change from baseline in low- and high-density lipoprotein cholesterol was generally comparable between LATAM and RoW populations. CONCLUSION: Upadacitinib 15 mg QD demonstrated a consistent safety profile across LATAM and RoW patient populations, with no new safety risks observed. TRIAL REGISTRATION NUMBERS: SELECT-EARLY, NCT02706873; SELECT-NEXT, NCT02675426; SELECT-COMPARE, NCT02629159; SELECT-MONOTHERAPY, NCT02706951; SELECT-BEYOND, NCT02706847; SELECT-CHOICE, NCT03086343.
Subject(s)
Antirheumatic Agents , Arthritis, Rheumatoid , Humans , Antirheumatic Agents/adverse effects , Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/chemically induced , Heterocyclic Compounds, 3-Ring/adverse effects , Latin America , Treatment OutcomeABSTRACT
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.
Subject(s)
Arthritis, Rheumatoid , Survival , Tumor Necrosis Factor-alpha , SpondylarthritisABSTRACT
OBJECTIVES: To describe the rate of infliximab discontinuation and the causes of this event in a population of rheumatoid arthritis patients. PATIENTS AND METHODS: Rheumatoid arthritis patients from an out-patient private center treated with infliximab (at least 2 consecutive doses) were retrospectively studied. The infliximab discontinuation rate was examined by the Kaplan-Meier survival method. Variables associated with infliximab discontinuation were analyzed by univariable and multivariable Cox proportional hazards regression analyses. RESULTS: Seventy-seven patients treated with infliximab between August 2000 and December 2006 were identified; of them, 33 (43%) discontinued this drug. The cumulative discontinuation rate was of 23%, 35%, and 43% at 12, 24, and 36 months, respectively. Causes of discontinuation were drug-related adverse reactions (41%), financial constraints (15%), lack of efficacy (12%), and others (32%). Variables independently associated with infliximab discontinuation were the number of tender joints on an average during infliximab treatment [hazard ratio (HR) = 1.17, 95% confidence interval (CI) 1.05-1.31; P = 0.005] and the occurrence of any adverse reaction attributed to infliximab (HR = 2.86, 95% CI 1.37-7.19; P = 0.026), whereas having full pharmacy coverage for infliximab (HR = 0.32, 95% CI 0.13-0.79, P = 0.014) was protective. CONCLUSION: Forty-three percent of patients discontinued infliximab at 3 years; most of them because of adverse reactions and financial constraints. Rheumatologists should be aware that those patients with more active disease were also at higher risk of discontinuing infliximab.
