OBJECTIVE: To investigate the frequency and trajectories of individual patients with polyarticular-course juvenile idiopathic arthritis (JIA) achieving novel composite end points on abatacept. METHODS: Data from a clinical trial of subcutaneous abatacept (NCT01844518) and a post hoc analysis of intravenous abatacept (NCT00095173) in patients with polyarticular-course JIA were included. Three end points were defined and evaluated: combined occurrence of low disease activity (LDA) measured by the Juvenile Arthritis Disease Activity Score; 50% improvement in American College of Rheumatology criteria for JIA (ACR50); and patient-reported outcomes. Patient-reported outcomes included visual analog scale score of minimal pain (pain-min) and Childhood Health Assessment Questionnaire disability index score of 0 (C-HAQ DI0). In this post hoc analysis, maintenance of month 13 and 21 end points (LDA+pain-min, LDA+C-HAQ DI0, and ACR50+pain-min) in those who achieved them at month 4 was determined. RESULTS: Composite end points (LDA+pain-min, LDA+C-HAQ DI0, and ACR50+pain-min) were achieved at month 4 (44.7%, 19.6%, and 58.9% of the 219 patients treated with subcutaneous abatacept, respectively). Of those who achieved LDA+pain-min at month 4, 84.7% (83 of 98) and 65.3% (64 of 98) maintained LDA+pain-min at months 13 and 21, respectively. The proportions of patients meeting LDA+pain-min outcomes increased from 44.7% (98 of 219) at month 4 to 54.8% (120 of 219) at month 21. The frequency of patients who met an LDA+C-HAQ DI score of 0 increased from 19.6% (43 of 219) at month 4 to 28.8% (63 of 219) at month 21. CONCLUSION: Among individual patients with polyarticular-course JIA treated with abatacept who achieved 1 of the combined clinical and patient-reported outcomes composite end points, many maintained them over 21 months of abatacept treatment.
Antirheumatic Agents , Arthritis, Juvenile , Humans , Child , Abatacept/adverse effects , Arthritis, Juvenile/diagnosis , Arthritis, Juvenile/drug therapy , Antirheumatic Agents/adverse effects , Treatment Outcome , Pain
OBJECTIVE: To investigate the pharmacokinetics, effectiveness, and safety of subcutaneous (SC) abatacept treatment over 24 months in patients with polyarticular-course juvenile idiopathic arthritis (JIA). METHODS: In this phase III, open-label, international, multicenter, single-arm study, patients with polyarticular JIA (cohort 1, ages 6-17 years and cohort 2, ages 2-5 years) in whom treatment with ≥1 disease-modifying antirheumatic drug was unsuccessful received weight-tiered SC abatacept weekly: 10 to <25 kg (50 mg), 25 to <50 kg (87.5 mg), ≥50 kg (125 mg). Patients who had met the JIA-American College of Rheumatology 30% improvement criteria (achieved a JIA-ACR 30 response) at month 4 were given the option to continue SC abatacept to month 24. The primary end point was the abatacept steady-state serum trough concentration (Cminss ) in cohort 1 at month 4. Other outcome measures included JIA-ACR 30, 50, 70, 90, 100, and inactive disease status, the median Juvenile Arthritis Disease Activity Score in 71 joints using the C-reactive protein level (JADAS-71-CRP) over time, safety, and immunogenicity. RESULTS: The median abatacept Cminss at month 4 (primary end point) and at month 24 was above the target therapeutic exposure (10 µg/ml) in both cohorts. The percentage of patients who had achieved JIA-ACR 30, 50, 70, 90, or 100 responses or had inactive disease responses at month 4 (intent-to-treat population) was 83.2%, 72.8%, 52.6%, 28.3%, 14.5%, and 30.1%, respectively, in cohort 1 (n = 173) and 89.1%, 84.8%, 73.9%, 58.7%, 41.3%, and 50.0%, respectively, in cohort 2 (n = 46); the responses were maintained to month 24. The median (interquartile range) JADAS-71-CRP improved from baseline to month 4: cohort 1, from 21.0 (13.5, 30.3) to 4.6 (2.1, 9.4); cohort 2, from 18.1 (14.0, 23.1) to 2.1 (0.3, 4.4). Improvements were sustained to month 24, at which time 27 of 173 patients (cohort 1) and 11 of 22 patients (cohort 2) had achieved JADAS-71-CRP remission. No unexpected adverse events were reported; 4 of 172 patients (2.3%) in cohort 1 and 4 of 46 (8.7%) in cohort 2 developed anti-abatacept antibodies, with no clinical effects. CONCLUSION: Weight-stratified SC abatacept yielded target therapeutic exposures across age and weight groups, was well tolerated, and improved polyarticular JIA symptoms over 24 months.
Abatacept/administration & dosage , Arthritis, Juvenile/drug therapy , Immunosuppressive Agents/administration & dosage , Adolescent , Arthritis, Juvenile/immunology , Child , Child, Preschool , Cohort Studies , Female , Humans , Injections, Subcutaneous , Male , Treatment Outcome
Objetivo: El objetivo del presente trabajo fue estudiar la sobrevida general y renal de la población pediátrica atendida con diagnóstico de Lupus eritematoso sistémico (LES), durante noviembre de 1991 y octubre del 2001, en el Instituto de Salud del Niño (ISN). Material y Métodos: Se realizó un estudio longitudinal y analítico de una serie de casos, donde se revisaron las historias clínicas de 102 pacientes, atendidos entre Noviembre del 91 y Octubre del 01 y que cumplieran con tener 4 ó más criterios utilizados por el Colegio Americano de Reumatología (CAR), edad menor de 18 años y tener dentro de estos criterios Anticuerpos Antinucleares y/o Anti DNA positivos. Resultados: De 102 pacientes, 89 fueron de sexo femenino (87%) y 13 de sexo masculino (13%), con una relación femenino/masculino de 7:1, la edad de presentación más frecuente estuvo entre los 10 y 14 años (57%). Se realizó biopsia renal en 56 pacientes, siendo la Glomérulonefritis proliferativa difusa (tipo IV) el tipo histológico más frecuente (60%). La sobrevida general a los 2 años de seguimiento fue de 94%. Los factores asociados a la mortalidad fueron la serositis y el compromiso renal (p<0.005). Las causas de fallecimiento fueron sepsis, neumonía, insuficiencia renal y edema agudo pulmonar y ocurrieron dentro de los dos primeros años de seguimiento. La sobrevida renal al 1, 2, 4 y 5 años fue de 92%,86%,81 % y 69% respectivamente. Llegaron a la muerte renal 13 pacientes (13%). Encontrándose como factores asociados, la edad mayor ó igual a 14 años, el tipo histológico IV y el tener 4 ó más criterios (p<0.001). Conclusiones: La sobrevida general a los 2 años de seguimiento fue 94% .La serositis y el compromiso renal fueron factores asociados a la mortalidad en los pacientes con diagnóstico de LES infantil. La sobrevida renal al año y a los 5 años fue 92% y 69% respectivamente. Factores altamente asociados a muerte renal fueron la edad.
Objective: The purpose of this research was to study the renal and general survival with LES diagnosis population under 18 years old, between November 91 and October 01 at the ISN. Methods and Materials: Analytical and longitudinal research was developed. The clinical histories of 102 patients were revised who were attended between November_91 and October 01 that fulfill the criterions of inclusion Iike to have 4 or more criterions used by American College of Rheumatology (RCA) , minor age of 18 years old and antinuclear antibody positive y/o anti DNA +. Results: Of the 102 patients enrolled in this study 89 were female (87%) and 13 were ma le patients (13%).The age rate of illness presentation was 10 14 years old (57%). Renal Biopsy was made in 56 patients and the type IV (GNDL) was the most frequent. General survival of 2 years was 94%.The associated factors with mortality were serositis and renal involvement (p<0.005). Renal survival of 1,2,4 and 5 years was 92%, 86%, 81% and 69% respectively. Associated renal survival factors were age, type IV (GNDL), four or more criterions as a higher level of sign ificance. Five of 102 patients died. Three patients from infectious causes : two due to sepsis, 1 due to pneumonia, 1 due to renal failure and 1 due to pulmonary edema within the first 2 years of follow up. Conclusions: The general survival of 2 years was 94%.The serositis and renal involvement were associated with mortal ity in the patients with LES diagnosis. The renal survival of 1 and 5 years was 92% and 69%. The age, type IV of renal biopsy, 4 or more criterions were high associated factors.
Male , Female , Humans , Adolescent , Child , Lupus Erythematosus, Systemic/diagnosis , Kidney Diseases , Survival
