Intravenous Golimumab in Children with Polyarticular-Course Juvenile Idiopathic Arthritis: Long-term Extension of an Open-label, Phase 3 Study.

OBJECTIVE: Report pharmacokinetics, immunogenicity, clinical effect, and safety of intravenous golimumab in children with active polyarticular-course juvenile idiopathic arthritis (pcJIA) who participated in the GO-VIVA study open-label long-term extension (LTE) through Week 252. METHODS: GO-VIVA participants who continued intravenous golimumab (80 mg/m2 every 8 weeks) after Week 52 were included. Pharmacokinetics and safety were assessed through Week 244 (last dose) and Week 252, respectively, and clinical response through Week 116. Clinical outcomes included JIA American College of Rheumatology (ACR) responses and clinical Juvenile Arthritis Disease Activity Score based upon 10 joints (cJADAS-10). Binary outcomes used nonresponder imputation; other descriptive analyses used observed data. RESULTS: Of 112/127 (88.2%) participants entering the LTE, 69 completed the Week-252 visit. Median steady-state trough golimumab concentrations were generally maintained from Weeks 52 through 244 (range, 0.3-0.6 µg/mL). Anti-golimumab antibody rates were consistent through Week 52 (39.2% [49/125]) and Week 244 (44.8% [56/125]). Week-52 JIA ACR 30/50/70/90 response rates (75.6% [96/127]/74.0% [94/127]/65.4% [83/127]/48.8% [62/127], respectively) were generally maintained through Week 116 (72.4% [92/127]/71.7% [91/127]/63.8% [81/127]/50.4% [64/127], respectively), when the median cJADAS-10 was 1.6 and 56.7% (72/127) of participants achieved JADAS-10 ≤5 (minimal disease activity). Rates (per 100 patient-years) of serious adverse events and serious infections through Week 252 were 7.7 and 3.9, respectively. CONCLUSION: GO-VIVA LTE participants experienced adequate pharmacokinetic exposure and stable safety and immunogenicity. The majority of participants experienced no more than minimal residual disease activity. Data suggest intravenous golimumab treatment provided durable clinical response through Week 116, with an acceptable benefit-risk profile.

Hydroxychloroquine blood levels predicts flare in childhood-onset lupus nephritis.

OBJECTIVE: Low hydroxychloroquine (HCQ) blood levels are predictors of flare in adult lupus. Childhood-onset systemic lupus erythematosus (cSLE) has high morbidity with renal involvement in up to 80% of cases. The aim of this study is to determine the HCQ cut-off levels which predicts flare in childhood-onset lupus nephritis (LN). METHODS: Sixty LN patients on HCQ use for at least 6-months were prospectively evaluated at baseline (BL) and about 6-months later for cSLE flare and HCQ blood levels (ng/mL) measured by liquid chromatography-tandem mass spectrometry. RESULTS: There were 19 patients (32%) with flare, during the study with median SLEDAI increase of 4 (0-8). Median (IQR) BL HCQ levels of the flare group were lower compared to stable patients [557.5 (68.6-980.3) vs. 1061.9 (534.8-1590.0 ng/mL); p=0.012]. ROC curve analysis demonstrated that HCQ levels≤1075 ng/mL were associated with a 5.08 (95%CI 1.28-20.13; p=0.021) times increased risk of flare. Six-month HCQ levels revealed that most patients 24/54 (44%) had persistently low levels (≤1075) during follow-up. Among those, 11/24 (46%) had flare. Multiple logistic regression analysis including prednisone use, baseline SLEDAI-2K, adherence based on pharmacy refill and BL HCQ blood levels as possible predictors of flare revealed that only HCQ blood level was independently associated with flare (OR 0.999, 95%CI 0.998-1.0, p=0.013). CONCLUSIONS: We demonstrated that HCQ blood cut-off level under 1075 ng/mL predicts flare in childhood-onset LN patients under prescribed HCQ dose of 4.0-5.5 mg/kg/day. We further observed that most of these patients have compliance issues reinforcing the need for a close surveillance particularly in those with levels below the defined cut-off.

Yellow fever vaccination in Brazil: Short-term safety and immunogenicity in juvenile autoimmune rheumatic diseases.

Yellow fever vaccine (YFV) is a live attenuated vaccine usually contraindicated for juvenile autoimmune rheumatic disease (JARD) patients. During the recent epidemic in Sao Paulo-Brazil, YFV was indicated for patients under low immunosuppression. Thirty JARD patients with inactive diseases undergoing low immunosuppression and 30 healthy controls (HC) were vaccinated with a fractional dose 17DD YFV (∼5495 IU) and evaluated 30 days later. JARD patients and controls had comparable median age (12.4 vs. 12 years, p = 0.250). Disease parameters remained stable 30 days after 17DD YFV (p > 0.05) and only mild adverse events were reported in both groups (p > 0.05). JARD and HC had similar seroprotection [93% vs. 100%;p = 0.49], seroconversion rates [96% vs. 100%;p = 0.489], and GMT [1249 vs.1293;p = 0.821]. Both groups had similar white-blood-cells kinetics with transient decreases in lymphocytes at D5 and neutrophils at D10, followed by full recovery at D30 (P < 0.05). In conclusion, 17DD YFV was safe and immunogenic in JARD. This study may contribute to recommendations for patients living/travelling to endemic areas.