Treatment of rheumatoid arthritis with recombinant human interleukin-1 receptor antagonist

This model is envisioned to study distinct aspects of human destructive joint diseases under in vitro conditions and to replace and/or supplement animal experiments in basic research and drug testing. Based on the fact that proinflammatory cytokines enhance destruction whereas IL-1Ra and antibodies against IL-1beta and CD44 inhibit the process, it is concluded that anti-IL-1- and anti-CD44-directed therapies may help prevent cartilage destruction in RA.

Section: Discussionsupporting

confidence: 66%

Anti-interleukin-1 and anti-CD44 interventions producing significant inhibition of cartilage destruction in an in vitro model of cartilage invasion by rheumatoid arthritis synovial fibroblasts

Neidhart¹,

Gay²,

Gay³

2000

“…The benefit of SSZ and LEF treatments in protocol MN301 was evident after only 6 months of therapy. A few other studies have demonstrated radiographic slowing after 6 months of treatment, but many investigators have continued to hold the view that trials should be 1 year or longer to improve the chances of demonstrating positive treatment effects on radiographic measures (3,4,23). Until data are available to allow power calculations on 6-month versus 1-or 2-year trials, this problem will not be resolved.…”

Section: Discussionmentioning

confidence: 99%

Treatment with leflunomide slows radiographic progression of rheumatoid arthritis: Results from three randomized controlled trials of leflunomide in patients with active rheumatoid arthritis

Sharp

Strand

Leung

et al. 2000

238

106

on behalf of the LEFLUNOMIDE RHEUMATOID ARTHRITIS INVESTIGATORS GROUP Objective. To determine whether treatment with leflunomide (LEF), methotrexate (MTX), or sulfasala-zine (SSZ) for 6-12 months retards progression of radiographic damage and to identify clinical variables that correlate with radiographic progression. Methods. Radiographs of the hands and feet were performed at baseline and at the end of study or early exit in 3 randomized controlled trials. Protocol US301 was a 12-month controlled trial of LEF or MTX treatment compared with placebo in 482 patients random-ized in a 3:3:2 ratio. Protocol MN301 compared 6 months of LEF or SSZ treatment with placebo in 358 patients, randomized in a 3:3:2 ratio, with continued blinded treatment in the active control arms for 12 months. Protocol MN302 compared 12 months of LEF treatment with MTX in 999 patients. Radiographs were blinded for sequence and treatment and were scored for erosions and joint space narrowing. All analyses were by intent-to-treat. Sensitivity analyses were performed to account for missing data. Results. LEF, MTX, and SSZ treatment resulted in statistically significantly less radiographic progression compared with placebo at 6 and 12 months: for protocol US301, LEF versus placebo P 0.0007 and MTX versus placebo P 0.0196; for protocol MN301, LEF versus placebo P 0.0004 and SSZ versus placebo P 0.0484. The effect of LEF treatment was similar to that of MTX and SSZ. Conclusion. These are the first 6-and 12-month randomized placebo-and active drug-controlled trials to demonstrate retardation of radiographic progression by a new disease-modifying antirheumatic drug (DMARD), LEF, as well as 2 commonly used DMARDs, MTX and SSZ.

“…Analyses of synovial biopsy specimens have revealed a clear relationship between the number of macrophages in the infiltrate and the activity of arthritis in adult-onset rheumatoid arthritis (RA) (1,2). In addition, RA is partly sensitive to treatments aimed at suppression of effector mechanisms of macrophages, e.g., inhibition of interleukin-1-or tumor necrosis factor (TNF)-mediated inflammatory effects (4)(5)(6). An unsolved problem in the treatment of chronic inflammatory diseases lies in adjusting the degree of the immunosuppressive therapy to the actual disease activity.…”

mentioning

confidence: 99%

Myeloid-related proteins 8 and 14 are specifically secreted during interaction of phagocytes and activated endothelium and are useful markers for monitoring disease activity in pauciarticular-onset juvenile rheumatoid arthritis

Frosch

Strey

Vogl

et al. 2000

358

286