Objectives Assess efficacy, pharmacokinetics (PK), and safety of intravenous (IV) golimumab in patients with polyarticular-course juvenile idiopathic arthritis (pc-JIA). Methods Children aged 2 to < 18 years with active pc-JIA despite methotrexate therapy for ≥2 months received 80 mg/m2 golimumab at Weeks 0, 4, then every 8 weeks through week 52 plus methotrexate weekly through week 28. The primary and major secondary endpoints were PK exposure and model-predicted steady-state area under the curve (AUCss) over an 8-week dosing interval at Weeks 28 and 52, respectively. JIA American College of Rheumatology (ACR) response and safety were also assessed. Results In total, 127 children were treated with IV golimumab. JIA ACR 30, 50, 70, and 90 response rates were 84%, 80%, 70%, and 47%, respectively, at week 28 and were maintained through week 52. Golimumab serum concentrations and AUCss were 0.40 µg/ml and 399 µg·day/ml at week 28. PK exposure was maintained at week 52. Steady-state trough golimumab concentrations and AUCss were consistent across age categories and comparable to IV golimumab dosed 2 mg/kg in adults with rheumatoid arthritis. Golimumab antibodies and neutralizing antibodies were detected via a highly sensitive drug-tolerant assay in 31% (39/125) and 19% (24/125) of patients, respectively. Median trough golimumab concentration was lower in antibody-positive vs antibody-negative patients. Serious infections were reported in 6% of patients, including 1 death due to septic shock. Conclusion Body surface area-based dosing of IV golimumab was well tolerated and provided adequate PK exposure for clinical efficacy in paediatric patients with active pc-JIA. ClinicalTrials.gov number NCT02277444

Objective: To evaluate prevalence, clinical manifestations, laboratory abnormalities and treatment in a multicenter cohort study including 847 childhood-onset systemic lupus erythematosus (cSLE) patients with and without diffuse alveolar hemorrhage (DAH), as well as concomitant parameters of severity. Methods: DAH was defined as the presence of at least three respiratory symptoms/signs associated with diffuse interstitial/alveolar infiltrates on chest x-ray or high-resolution computer tomography and sudden drop in hemoglobin levels. Statistical analysis was performed using Bonferroni correction (p < 0.0022). Results: DAH was observed in 19/847 (2.2%) cSLE patients. Cough/dyspnea/tachycardia/hypoxemia occurred in all cSLE patients with DAH. Concomitant parameters of severity observed were: mechanical ventilation in 14/19 (74%), hemoptysis 12/19 (63%), macrophage activation syndrome 2/19 (10%) and death 9/19 (47%). Further analysis of cSLE patients at DAH diagnosis compared to 76 cSLE control patients without DAH with same disease duration [3 (1-151) vs. 4 (1-151) months, p = 0.335], showed higher frequencies of constitutional involvement (74% vs. 10%, p < 0.0001), serositis (63% vs. 6%, p < 0.0001) and sepsis (53% vs. 9%, p < 0.0001) in the DAH group. The median of disease activity score(SLEDAI-2 K) was significantly higher in cSLE patients with DAH [18 (5-40) vs. 6 (0-44), p < 0.0001]. The frequencies of thrombocytopenia (53% vs. 12%, p < 0.0001), intravenous methylprednisolone (95% vs. 16%, p < 0.0001) and intravenous cyclophosphamide (47% vs. 8%, p < 0.0001) were also significantly higher in DAH patients. Conclusions: This was the first study to demonstrate that DAH, although not a disease activity score descriptor, occurred in the context of significant moderate/severe cSLE flare. Importantly, we identified that this condition was associated with serious disease flare complicated by sepsis with high mortality rate.

ResumoObjetivo: Caracterizar a atividade inflamatória articular e sistêmica na artrite idiopática juvenil (AIJ), determinando o estado de remissão com e sem uso de medicação.Métodos: Um total de 165 casos de AIJ, acompanhados em média por 3,6 anos, foram revisados para caracterização de episódios de inatividade, remissão clínica com e sem medicação. Os dados obtidos foram analisados por meio de estatística descritiva, análise de sobrevida, comparação das curvas de Kaplan-Meier, teste de log rank e análise de regressão logística binária para determinação de fatores preditivos para a remissão ou atividade persistente.

The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new parent/patient reported outcome measure that enables a thorough assessment of the disease status in children with juvenile idiopathic arthritis (JIA). We report the results of the cross-cultural adaptation and validation of the parent and patient versions of the JAMAR in the Brazilian Portuguese language. The reading comprehension of the questionnaire was tested in 10 JIA parents and patients. Each participating centre was asked to collect demographic, clinical data and the JAMAR in 100 consecutive JIA patients or all consecutive patients seen in a 6-month period and to administer the JAMAR to 100 healthy children and their parents. The statistical validation phase explored descriptive statistics and the psychometric issues of the JAMAR: the three Likert assumptions, floor/ceiling effects, internal consistency, Cronbach’s alpha, interscale correlations, test–retest reliability, and construct validity (convergent and discriminant validity). A total of 231 JIA patients (14.7% systemic, 43.3% oligoarticular, 22.5% RF negative polyarthritis, 19.5% other categories) and 72 healthy children, were enrolled in three centres. The JAMAR components discriminated well healthy subjects from JIA patients. All JAMAR components revealed good psychometric performances. In conclusion, the Brazilian Portuguese version of the JAMAR is a valid tool for the assessment of children with JIA and is suitable for use both in routine clinical practice and clinical research.