Anakinra in the treatment of polyarticular-course juvenile rheumatoid arthritis: safety and preliminary efficacy results of a randomized multicenter study

Abstract

This study assessed the safety and preliminary efficacy of the interleukin-1 receptor antagonist anakinra in patients with polyarticular-course juvenile rheumatoid arthritis (JRA). Eighty-six patients entered a 12-week open-label run-in phase (1 mg/kg anakinra daily, ≤100 mg/day). Fifty responders were randomized to anakinra or placebo in a 16-week blinded phase, followed by a 12-month open-label extension (N=44). Due to low enrollment, the primary endpoint was changed from efficacy to safety. The incidence and nature of adverse events were similar across all study phases, with the exception of injection site reactions, which were mild to moderate and decreased with time. Anakinra produced a nonsignificant (P=0.11) reduction in disease flares compared with placebo. When normalized to 1 mg/kg dose, anakinra plasma concentrations were similar to values in adult patients with rheumatoid arthritis. These results indicate that anakinra 1 mg/kg once daily (≤100 mg/day) is safe and well tolerated in patients with JRA.

HDAC Inhibition in Rheumatoid Arthritis and Juvenile Idiopathic Arthritis

“…This fact indicates that HDACi, as shown in givinostat study, could replace MTX in nonresponsive or intolerant patients by targeting systemic as well as local disease. A randomized controlled trial of anakinra (1 mg/kg; maximum 100 mg/ day) versus placebo in 50 nonsystemic JIA patients was unable to demonstrate significant reduction of disease activity (34). Subgroup analysis, however, suggested that response rates may be higher among patients with systemic disease (34).…”

“…A randomized controlled trial of anakinra (1 mg/kg; maximum 100 mg/ day) versus placebo in 50 nonsystemic JIA patients was unable to demonstrate significant reduction of disease activity (34). Subgroup analysis, however, suggested that response rates may be higher among patients with systemic disease (34). In another study (29), 15 of 20 patients showed an initial response to anakinra, with improvement in systemic and laboratory features of SOJIA, but with less efficacy in terms of arthritis.…”

New Treatment Strategies in the Treatment of Juvenile Idiopathic Arthritis

“…In an open-label study by Reiff, [56] 80 patients with various forms of JIA were treated with anakinra; patients with SOJIA had a better response to anakinra than did those with other types of JIA (11/15 responded to anakinra). A similar recent RCT of anakinra (1mg/kg/day; maximum 100 mg/day) versus placebo in 50 patients with JIA by Ilowite et al [57] was unable to demonstrate significant efficacy of the drug. Subgroup analysis, however, showed that response rates may be higher among patients with SOJIA.…”

Treatment in juvenile rheumatoid arthritis and new treatment options

“…Although the rash spontaneously improves in time, improvement can be provided more rapidly with cold application. Rare cases of neutropenia and hepatotoxicity have been reported (27). Opportunistic infection has not been reported so far; pneumonia, bacteriemia, local skin infections and herpes simplex virus infections have been reported (28).…”