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Background/Purpose: To assess efficacy and safety of SC golimumab (GLM) in polyarticular pediatric juvenile idiopathic arthritis pts (aged 2 to <18 yrs) with active arthritis despite MTX for ≥3 months. Methods: In GO-KIDS, a 3-part randomized double-blind, PBO-controlled, withdrawal trial in pts with active JIA with a polyarticular course (≥5 active joints) and disease duration of ≥6 months despite current MTX (10-30 mg/m2/wk). In Part 1(wk 0-12), all pts received open-label (OL) 30 mg/m2 GLM SC (max 50 mg) q4 wks with stable MTX dose. At wk 16, pts with ACR JIA 30 response entered Part 2 (wk 16-48). In Part 2, pts were randomized to continue GLM or switch to PBO q4 wks. Upon Part 2 completion at wk 48 or ACR JIA flare in Part 2, pts received OL GLM in Part 3. Primary endpoint was proportion of ACR JIA 30 responders at wk 16 without a JIA flare in Part 2 using wk 16 as baseline measurement. Secondary outcomes were ACR JIA 30/50/70/90 response rates and inactive disease rates at wk 16 and wk 48 by group and safety. Results: 173 pts (Caucasian 87.9%, 75.7% females; age [median/range] 12 yrs/2-17 yrs) with moderately active disease were enrolled (Table ); 19 (11%) were d/c in Part 1 (lack of efficacy n = 14, AE n = 4, withdrawal of consent n = 1). In Part 1, 151 of 173 (87.3%) achieved an ACR JIA 30 response and 36.1% inactive disease status (Table ). There were 154 pts randomized double-blind in Part 2 (PBO n = 76; continued GLM n = 78). At the end of Part 2, no significant differences between groups in JIA ACR non-flare rates and trial did not meet primary endpoint [PBO-grp vs. GLM-grp: 52.6% vs. 59.0%, p = 0.41) nor were there differences for major secondary endpoints (Table 2). In contrast, sustained response in both groups (PBO, GLM) relative to wk 0 (Table 1 and 2). 6.5% (10 of 154) of pts d/c therapy after wk16 through wk 48. Through wk 48, AEs, serious AE (SAE), and serious infections were reported in 87.9%, 13.3%, and 2.9% of all randomized pts, respectively. Most common SAE was JIA exacerbation. No deaths, active TB or malignancies were reported (1). GLM-treated pt experienced SAE of toxic hepatitis and 1 had SAE of hepatic enzyme increase. One pt switched from PBO to GLM experienced SAE of serum sickness reaction, resulting in GLM d/c. Proportion of pts with ≥1 injection site reaction was 8.1%. None of the reactions were serious, severe, or led to GLM d/c. [ABSTRACT FROM AUTHOR]

Background/Purpose: Tocilizumab (TCZ) treatment has been associated with reduced neutrophil counts in adults with rheumatoid arthritis and in children with systemic juvenile idiopathic arthritis. The aims of this study were to assess changes in neutrophil counts, determine whether neutropenia was associated with increased risk for infection, and investigate variables associated with the development of neutropenia in patients with polyarticular-course juvenile idiopathic arthritis (pcJIA) receiving TCZ for up to 2 years in the CHERISH trial. Methods: One hundred eighty-eight patients (2-17 years) with active pcJIA and inadequate response to methotrexate received open-label (OL) TCZ according to body weight (BW) (BW ≥30 kg, TCZ 8 mg/kg; BW <30 kg, randomly assigned 1:1 to TCZ 8 or 10 mg/kg) every 4 weeks for 16 weeks. Patients who achieved ≥JIA ACR30 response at 16 weeks entered a 24-week, randomized, double-blind withdrawal period and were assigned 1:1 to placebo or continued TCZ. Patients who experienced JIA ACR flare or who completed the withdrawal period entered an OL extension through week 104. Blood cell counts were monitored every 4 weeks. Worst Common Toxicity Criteria (CTC) neutrophil grade and lowest observed neutrophil count (109/L) were identified for each patient. Rates of infection and serious infection (per 100 patient-years [PY]) in periods ±30 days around grade 1/2 and around grade 3/4 neutrophil counts were compared with corresponding rates in periods with normal neutrophil counts. Univariate linear regression analysis was used in patients enrolled in part 3 of the study to investigate the association between patient baseline characteristics and lowest observed neutrophil count from baseline to week 104. Results: At baseline, all patients had neutrophil counts within or above the normal range. Median neutrophil count decreased during the first 16 weeks of treatment and stabilized for the remainder of the study. Throughout the 2-year study, 118 patients (62.8%) had normal neutrophil counts, whereas CTC grades 1, 2, 3, and 4 neutrophil counts were reported in 15 (8.0%), 44 (23.4%), 11 (5.9%), and 0 (0.0%) patients, respectively. Infections and serious infections occurred at rates of 151.4/100 PY and 5.2/100 PY, respectively. All serious infection events (n = 16) occurred during periods of normal neutrophil count. Rates of infection during periods of normal, grade 1/2, and grade 3 neutrophil count were 147.8/100 PY (95% CI, 133.9-162.7), 176.6/100 PY (95% CI, 128.8-236.3), and 340/100 PY (95% CI, 136.7-700.5), respectively, with largely overlapping confidence intervals. Low neutrophil count was not associated with any baseline covariates investigated. Conclusion: In the CHERISH trial, there was no evidence of increased rates of serious infection associated with low neutrophil count. The prevalence of neutropenia in the pcJIA population was lower than in other disease groups (eg, systemic JIA) treated with TCZ. [ABSTRACT FROM AUTHOR]

Background/Purpose: Lupus nephritis (LN) is frequently associated with a poor long-term prognosis. Current non-invasive blood and urine tests do not reliably predict the course of LN. The objective of this study was to evaluate the performance of candidate urine biomarkers in predicting future kidney function in adults and children with LN. The biomarker candidates studies were liver-type fatty acid binding protein (L-FABP), albumin (Alb), monocyte chemoattractant protein 1 (MCP-1), Uromodulin, Transferrin and Hepcidin. Methods: L-FABP, Alb, MCP-1, Uromodulin, Transferrin and Hepcidin were measured by ELISA in urine from 70 adults and 42 children collected at the time of enrollment into prospective observational LN cohorts. Urine analytes were normalized to urine creatinine and logarithmically transformed. The association of each analyte to renal function loss (RFL), defined as a sustained increase of ≥25% in serum creatinine (SCr; adults) or a decrease in eGFR of ≥20% (children), was determined using a fixed effect model after adjusting for the age group (adult vs. child). In addition, the results were confirmed using Wilcoxon Rank Sum tests. Logistical models were used to predict the presence of RFL using each biomarker or a combination of the biomarkers. Biomarker performance in predicting RFL was assessed as the area under a ROC curve (AUC) corresponding to the logistical model. Results: 13 children and 22 adults had RFL during the mean follow-up period of 6.1 months and 60 months, respectively. Overall patients with RFL showed significantly higher levels ALB than those without RFL (p < 0.05, ). In addition, the levels of L-FABP, MCP-1, and Transferrin were also marginally higher in RFL (p-values < 0.1). The AUC using the combination of urine L-FABP, Alb, MCP-1 and Utransferrin was 0.66, slightly higher than those using any single biomarker as the predictor (ranging from 0.52-0.63). [ABSTRACT FROM AUTHOR]