Absence of Association Between Abatacept Exposure and Initial Infection in Patients With Juvenile Idiopathic Arthritis.

OBJECTIVE: To assess the relationship between infection risk and abatacept (ABA) exposure levels in patients with polyarticular-course juvenile idiopathic arthritis (pJIA) following treatment with subcutaneous (SC) and intravenous (IV) ABA. METHODS: Data from 2 published studies (ClinicalTrials.gov: NCT01844518, NCT00095173) of ABA treatment in pediatric patients were analyzed. One study treated patients aged 2-17 years with SC ABA and the other treated patients aged 6-17 years with IV ABA. Association between serum ABA exposure measures and infection was evaluated using Kaplan-Meier plots of probability of first infection vs time on treatment by ABA exposure quartiles and log-rank tests. Number of infections by ABA exposure quartiles was investigated. RESULTS: Overall, 343 patients were included in this analysis: 219 patients received SC ABA and 124 patients received IV ABA. Overall, 237/343 (69.1%) patients had ≥ 1 infection over 24 months. No significant difference in time to first infection across 4 quartiles of ABA exposure levels was observed in the pooled (P = 0.45), SC (2-5 yrs: P = 0.93; 6-17 yrs: P = 0.48), or IV (P = 0.50) analyses. Concomitant use of methotrexate and glucocorticoids (at baseline and throughout) with ABA did not increase infection risk across the ABA exposure quartiles. There was no evidence of association between number of infections and ABA exposure quartiles. No opportunistic infections related to ABA were reported. CONCLUSION: In patients aged 2-17 years with pJIA, no evidence of association between higher levels of exposure to IV ABA or SC ABA and incidence of infection was observed.

Safety and efficacy of intravenous belimumab in children with systemic lupus erythematosus: results from a randomised, placebo-controlled trial.

OBJECTIVES: This ongoing Phase-2, randomised, placebo-controlled, double-blind study evaluated the efficacy, safety and pharmacokinetics of intravenous belimumab in childhood-onset systemic lupus erythematosus (cSLE). METHODS: Patients (5 to 17 years) were randomised to belimumab 10 mg/kg intravenous or placebo every 4 weeks, plus standard SLE therapy. Primary endpoint: SLE Responder Index (SRI4) response rate (Week 52). Key major secondary endpoints: proportion of patients achieving the Paediatric Rheumatology International Trials Organisation/American College of Rheumatology (PRINTO/ACR) response using 50 and '30 alternative' definitions (Week 52), and sustained response (Weeks 44 to 52) by SRI4 and Parent Global Assessment of well-being (Parent-global). Safety and pharmacokinetics were assessed. Study not powered for statistical testing. RESULTS: Ninety-three patients were randomised (belimumab, n=53; placebo, n=40). At Week 52, there were numerically more SRI4 responders with belimumab versus placebo (52.8% vs 43.6%; OR 1.49 (95% CI 0.64 to 3.46)). PRINTO/ACR 30 alternative (52.8% vs 27.5%; OR 2.92 (95% CI 1.19 to 7.17)) and PRINTO/ACR 50 (60.4% vs 35.0%; OR 2.74 (95% CI 1.15 to 6.54)) responses were more frequent with belimumab than placebo, as were sustained responses for SRI4 (belimumab, 43.4%; placebo, 41.0%; OR 1.08 (95% CI 0.46 to 2.52)) and Parent-global (belimumab, 59.1%; placebo, 33.3%; OR 3.49 (95% CI 1.23 to 9.91)). Serious adverse events were reported in 17.0% of belimumab patients and 35.0% of placebo patients; one death occurred (placebo). Week-52, geometric mean (95% CI) belimumab trough concentration was 56.2 (45.2 to 69.8) µg/mL. CONCLUSION: The belimumab intravenous pharmacokinetics and benefit-risk profile in cSLE are consistent with adult belimumab studies and the 10 mg/kg every 4 weeks dose is appropriate. TRIAL REGISTRATION NUMBER: NCT01649765.

Two randomized trials of canakinumab in systemic juvenile idiopathic arthritis.

BACKGROUND: Interleukin-1 is pivotal in the pathogenesis of systemic juvenile idiopathic arthritis (JIA). We assessed the efficacy and safety of canakinumab, a selective, fully human, anti-interleukin-1ß monoclonal antibody, in two trials. METHODS: In trial 1, we randomly assigned patients, 2 to 19 years of age, with systemic JIA and active systemic features (fever; ≥2 active joints; C-reactive protein, >30 mg per liter; and glucocorticoid dose, ≤1.0 mg per kilogram of body weight per day), in a double-blind fashion, to a single subcutaneous dose of canakinumab (4 mg per kilogram) or placebo. The primary outcome, termed adapted JIA ACR 30 response, was defined as improvement of 30% or more in at least three of the six core criteria for JIA, worsening of more than 30% in no more than one of the criteria, and resolution of fever. In trial 2, after 32 weeks of open-label treatment with canakinumab, patients who had a response and underwent glucocorticoid tapering were randomly assigned to continued treatment with canakinumab or to placebo. The primary outcome was time to flare of systemic JIA. RESULTS: At day 15 in trial 1, more patients in the canakinumab group had an adapted JIA ACR 30 response (36 of 43 [84%], vs. 4 of 41 [10%] in the placebo group; P<0.001). In trial 2, among the 100 patients (of 177 in the open-label phase) who underwent randomization in the withdrawal phase, the risk of flare was lower among patients who continued to receive canakinumab than among those who were switched to placebo (74% of patients in the canakinumab group had no flare, vs. 25% in the placebo group, according to Kaplan-Meier estimates; hazard ratio, 0.36; P=0.003). The average glucocorticoid dose was reduced from 0.34 to 0.05 mg per kilogram per day, and glucocorticoids were discontinued in 42 of 128 patients (33%). The macrophage activation syndrome occurred in 7 patients; infections were more frequent with canakinumab than with placebo. CONCLUSIONS: These two phase 3 studies show the efficacy of canakinumab in systemic JIA with active systemic features. (Funded by Novartis Pharma; ClinicalTrials.gov numbers, NCT00889863 and NCT00886769.).

Artitris séptica esternoclavicular / Sternoclavicular septic arthritis

Reportamos nueve pacientes con artritis séptica esternoclavicular (ASEC), dos de los cuales fueron adictos a drogas endovenosas, pero en ningún caso a heroína. La edad promedio fue de 34.5 años. El sexo más frecuente fue el masculino. En seis pacientes se aisló el microorganismo causal, siendo el más frecuente aislado el Stafilococo aureus. Ocho pacientes fueron tratados y tuvieron excelente respuesta

Compromiso osteoarticular asociado a Falciformismo / Osteoarticular involvement associated to sickle cell syndromes

Se reportan 6 pacientes con anemia falciforme (4 con Hb SS, 1 con Hb SC y 1 con Hb SB-talasemia), atendidos en el Hospital Nacional Cayetano Heredia entre 1983 y 1990, que presentaron diversas manifestaciones musculoesqueléticas en el curso de su evolución, resaltando dos casos de necrosis aséptica y un paciente con osteomielitis del fémur por Salmonella tiphy. se discuten los casos en relación a la literatura

Compromiso reumatológico (CR) en infección meningocócica / Rheumatological involvement in meningococcal infection

Se comunica la experiencia en el manejo del compromiso reumatológico en infección por Neisseria meningitidis en el HCH entre 1968 y 1988. Tuvimos 9 pacientes con compromiso musculoesquelético: poliartritis, oligoartritis y reumatismo extraarticular, con tiempo de aparición y duración variable. En todos, el cultivo de líquido sinovial fué negativo. El manejo divide a los pacientes en dos grupos, uno que responde con tratamiento antibiótico y drenaje articular y otro que requiere antiinflamatorios no esteroideos. El pronóstico fué bueno en todos.

Compromiso osteoarticular por cándida en neonatos / Osteoarticular compromise due to candida en neonatos

Artritis séptica por Candida albicans es una entidad reportada infrecuentemente, mayormente en pacientes inmunocomprometidos, neonatos y adictos a drogas parenterales. Nosotros reportamos 3 casos de artritis séptica debida a Candida albicans en neonatos vivos en el Hospital Cayetano Heredia entre 1987 y julio de 1989. Todos los pacientes presentaron enfermedades subyacentes y factores predisponentes previamente descritos asociados con infección por Candida. La forma monoarticular, mayormente de rodilla fue lo más común. La complicación de osteomielitis se observó en dos casos. La evolución fue favorable con el uso de Anfotericin-B y 5FC, dependiendo la evolución final de las entidades subyacentes condicionantes de la infección. La artritis por candida, aunque infrecuente, debería ser considerada en el diagnóstico diferencial de artritis séptica en todo paciente con condiciones de riesgo para el desarrollo de esta infección