Long-term efficacy and safety of infliximab plus methotrexate for the treatment of polyarticular-course juvenile rheumatoid arthritis: findings from an open-label treatment extension.

OBJECTIVE: To assess the long-term efficacy and safety of infliximab plus methotrexate in juvenile rheumatoid arthritis (JRA). METHODS: Patients eligible for the open-label extension (OLE, weeks 52-204) received infliximab 3-6 mg/kg every 8 weeks plus methotrexate. RESULTS: Of the 78/122 (64%) children entering the OLE, 42 discontinued infliximab, most commonly due to consent withdrawal (11 patients), lack of efficacy (eight patients) or patient/physician/sponsor requirement (eight patients). Infliximab (mean dose 4.4 mg/kg per infusion) was generally well tolerated. Infusion reactions occurred in 32% (25/78) of patients, with a higher incidence in patients positive for antibodies to infliximab (58%, 15/26). At week 204, the proportions of patients achieving ACR-Pedi-30/50/70/90 response criteria and inactive disease status were 44%, 40%, 33%, 24% and 13%, respectively. CONCLUSIONS: In the limited population of JRA patients remaining in the study at 4 years, infliximab was safe and effective but associated with a high patient discontinuation rate.

Complex genetic predisposition in adult and juvenile rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) and juvenile rheumatoid arthritis (JRA) are complex multifactorial diseases caused by environmental influences and an unknown number of predisposing genes. The present study was undertaken in order to investigate association of polymorphisms in candidate genes with RA and JRA in German subjects. RESULTS: Up to 200 unrelated German RA and JRA patients each and 300-400 healthy controls have been genotyped for HLA-DRB1, TNFa, TNFA -238a/g, TNFA -308a/g, TNFA -857c/t, TNFR1 -609g/t, TNFR1 P12P, TNFR2 del 15bp, IKBL -332a/g, IKBL -132t/a, IKBL C224R, CTLA4 -318c/t, CTLA4 T17A, PTPRC P57P, MIF -173g/c, the MIF and IFNG microsatellites as well as for D17S795, D17S807, D17S1821 by polyacrylamide gel electrophoresis, single-strand conformation polymorphism analysis, restriction fragment length polymorphism analysis or allele specific hybridization. None of the investigated genetic markers is associated with both, RA and JRA, but there are some statistically significant differences between patients and controls that have to be discussed sensibly. CONCLUSIONS: The difficulty in investigating the genetics of complex disorders like RA and JRA may arise from genetic heterogeneity in the clinically defined disease cohorts (and generally limited power of such studies). In addition, several to many genes appear to be involved in the genetic predisposition, each of which exerting only small effects. The number of investigated patients has to be increased to establish the possibility of subdivison of the patients according their clinical symptoms, severity of disease, HLA status and other genetic characteristics.