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Children with juvenile rheumatoid arthritis (JRA) may develop an acquired circulating inhibitor to blood clotting factor VIII (FVIII), which has also been found in hemophiliacs. JRA is a chronic disease of children involving inflammation of the joints. A 19-year-old man with JRA whose FVIII activity was found to be very low was then found to have the acquired FVIII inhibitor. Patients with acquired FVIII inhibitor usually have bleeding complications similar to those seen in hemophiliacs. Eighteen pediatric cases of acquired FVIII inhibitor were found in the literature, but only this case described JRA as well. Aggressive early treatment with corticosteroids and, later on, cyclophosphamide, was given to this patient. Although rare, it is suggested that acquired FVIII inhibitor be considered as a cause of bleeding disorder in children with JRA.

Objective: To evaluate changes in health-related quality of life (HRQoL) and disability in children with systemic juvenile idiopathic arthritis (JIA) or polyarticular JIA treated with tocilizumab.Methods: Secondary analyses of two double-blind, placebo-controlled trials of intravenous tocilizumab in children with active systemic JIA or polyarticular JIA were conducted. Patient-reported outcomes of disability (Childhood Health Assessment Questionnaire [C-HAQ]), HRQoL (Child Health Questionnaire Parent Form 50 [CHQ-P50], health concepts, physical summary score [CHQ-P50-PhS], psychosocial summary score [CHQ-P50-PsS]), pain, and well-being (100-mm visual analog scale [VAS]) were measured at weeks 0 and 12 for systemic JIA, weeks 16 and 40 for polyarticular JIA, and week 104 for both JIA subgroups.Results: The trial included 112 patients with systemic JIA and 188 patients with polyarticular JIA. In patients with polyarticular JIA, the mean ± SD C-HAQ score decreased from 1.39 ± 0.74 at baseline to 0.67 ± 0.65 at week 16 (P < 0.001). In patients with systemic JIA, the mean ± SD CHQ-P50-PhS improved more with tocilizumab therapy than with placebo at week 12 (7.3 ± 10.2 versus 2.4 ± 10.6) (P < 0.05). Almost all mean CHQ-P50 health concept scores, CHQ-P50-PsS, and CHQ-P50-PhS improved (P ≤ 0.002) by week 104 for patients with systemic JIA. Patients with polyarticular JIA and patients with systemic JIA showed significant reductions in disability (mean ± SD C-HAQ scores of -1.09 ± 0.71 and -1.17 ± 0.80, respectively), improvements in well-being (mean ± SD well-being VAS scores of -43.76 ± 26.61 and -51.53 ± 23.57, respectively), and decreases in pain (mean ± SD pain VAS scores of -41.56 ± 31.06 and -51.26 ± 26.79, respectively) (P < 0.001); in patients with polyarticular JIA and patients with systemic JIA who were treated with tocilizumab, 92.9% of polyarticular JIA patients and 96.8% of systemic JIA patients reported no more than minimal pain (a score of ≤35 mm on the VAS) at week 104.Conclusion: Tocilizumab treatment was associated with significantly reduced disability and pain and improved HRQoL in patients with systemic JIA and polyarticular JIA. [ABSTRACT FROM AUTHOR]

Objective To evaluate the persistence and effectiveness of TNF inhibitors (TNFi) vs non-TNFi among newly diagnosed JIA patients after initiation of biologic DMARD (bDMARD). Methods Using longitudinal patient-level data extracted from electronic medical records in a large Midwestern paediatric hospital from 2009 to 2018, we identified JIA patients initiating TNFi and non-TNFi treatment. Treatment effectiveness was assessed based on disease activity. Inverse probability of treatment weighting of propensity score was used to estimate the treatment effectiveness and Kaplan–Meier analyses were conducted to assess persistence. Results Of 667 JIA patients, most (92.0%) were prescribed one of the class of TNFi as their initial biologic treatment. Etanercept was the most frequently prescribed (67.1%) treatment, followed by adalimumab (27.5%). Only around 5% of patients were prescribed off-label bDMARDs as their first-course treatment; however, >20% were prescribed off-label biologics as their second-course therapy. Some 7.2% of patients received four or more bDMARDs. The median persistence of the first-course bDMARD is 320 days, with TNFi being significantly longer than the non-TNFi (395 vs 320 days, P  = 0.010). The clinical Juvenile Disease Activity Score (cJADAS) reduction of TNFi users (6.6, 95% CI 5.7, 7.5) was significant greater compared with non-TNFi users (3.0, 95% CI 1.5, 4.6, P  < 0.0001) at 6-month follow-up visit. Conclusion Persistence was significantly longer among patients initiating TNFi as their first biologic therapy than those receiving non-TNFi. Patients receiving TNF therapy had significant greater reduction of cJADAS at the 6-month follow-up visit compared with patients in the non-TNF cohort. [ABSTRACT FROM AUTHOR]

Abstract Background We evaluated the effect of infliximab on markers of inflammation in patients with juvenile idiopathic arthritis (JIA). Methods In this randomized, placebo-controlled substudy, 122 patients with JIA received infliximab 3 mg/kg + methotrexate (MTX)(n = 60) or placebo + MTX (n = 62) at weeks 0, 2, and 6. At week 14, patients receiving placebo + MTX crossed over to infliximab 6 mg/kg + MTX; patients receiving infliximab 3 mg/kg + MTX continued treatment through week 44. Sera and plasma from eligible patients receiving infliximab 3 mg/kg + MTX (n = 34) and receiving placebo→infliximab 6 mg/kg +MTX (n = 38) were collected at weeks 0, 2, 14, 16, 28, and 52 and analyzed for inflammatory markers (IL-6, IL-12p40, ICAM-1, MMP-3, VEGF, TNF-α, and CRP). Results At week 2, decreases from baseline in IL-6, ICAM-1, MMP-3, TNF-α, and CRP were greater with infliximab versus placebo treatment, and with the exception of CRP, these differences were generally maintained through week 14. The decreases from baseline to week 52 in IL-6, ICAM-1, VEGF, MMP-3, and CRP and increases in IL-12p40 levels were larger in patients receiving placebo→infliximab 6 mg/kg +MTX versus infliximab 3 mg/kg + MTX treatment. Patients receiving infliximab 3 mg/kg+MTX who achieved an American College of Rheumatology Pediatric 30 (ACR-Pedi-30) response had significantly larger decreases from baseline in ICAM-1 (p = 0.0105) and MMP-3 (p = 0.0253) at week 2 and in ICAM-1 (p = 0.0304), MMP-3 (p = 0.0091), and CRP (p = 0.0011) at week 14 versus ACR-Pedi-30 nonresponders. Conclusion Infliximab + MTX attenuated several inflammatory markers in patients with JIA; larger decreases in ICAM-1, MMP-3, and CRP levels were observed in ACR-Pedi-30 responders versus nonresponders. Trial Registration NCT00036374

Abstract Background Concerns have been raised about a potential link between the use of TNF inhibitors and development of malignancy in the pediatric population. We examined the worldwide experience of etanercept use in pediatric patients and the occurrence of malignancies as reported from clinical trials, registry studies, post-marketing surveillance, and published scientific literature. Methods All reports of "malignancy" in pediatric patients (including subjects who received etanercept before age 18 and developed a malignancy before age 22) were collected from the etanercept clinical trials database and global safety database using the Medical Dictionary for Regulatory Activities (MedDRA; v12.0) standardized MedDRA query "Malignancies" from 1998 to August 2009. Cases were collected irrespective of treatment indication. All cases were included regardless of exposure to other TNF blockers or other biologics and whether the other exposure was before or after etanercept. Results A total of 18 potential malignancies were identified: 4 leukemias, 7 lymphomas, and 7 solid tumors. Three of the 18 malignancies remain unconfirmed. No malignancies were reported from clinical trials or the open-label extension studies in any indication in children. Conclusion The data suggest that there does not appear to be an increased risk of malignancy overall with the use of etanercept. Among etanercept-exposed patients aged 4 to 17 years, the estimated worldwide and US reporting rates for lymphoma were approximately 0.01 per 100 patient-years (1 in 10,000 pt-yrs). While the reported rate of lymphoma is higher in pediatric patients treated with etanercept than in normal children, the expected rate of lymphoma in biologic naïve JIA patients is currently unknown. The risk of TNF inhibitors in the development of malignancies in children and adolescents is difficult to assess because of the rarity of malignant events, the absence of knowledge of underlying frequency of leukemia and lymphoma in JIA, and the confounding use of concomitant immunosuppressive medications.