Der Interleukin-1-Rezeptorantagonist Anakinra (Kineret�) in der Behandlung mit rheumatoider Arthritis

Abstract

New treatment strategies in rheumatoid arthritis are targeted to interfere with critical mediators of inflammation. Proinflammatory cytokines like IL-1 beta and TNFalpha play a crucial role in induction and maintenance of synovitis, pannus formation and bone and cartilage destruction. Within a few years, these morphological changes may lead to joint destruction and consecutively to functional impairment. Since April 2002 a recombinant human interleukin-1 receptor antagonist (Anakinra) is available in Germany for treatment of patients with rheumatoid arthritis. Anakinra (Kineret(R)) is approved for therapy in combination with methotrexate and should be applied according to guidelines established by the German Rheumatology Society for the use of biologicals in treatment of patients with rheumatoid arthritis. The approval of anakinra as a new therapeutic is based on data obtained in large multicenter, placebo-controlled, and randomised trials in comparison to placebo. Treatment of Anakinra as monotherapy or in combination with methotrexate lead to significant improvement of signs and symptoms of disease as measured by the ACR 20 (or more) response and was associated with a slower radiographic progression with regard to joint space narrowing and development of erosions. Anakinra showed a favourable safety profile with injection side reactions as the predominant side effect that occurs in 70% of patients usually after 10-12 days of treatment and that are mostly mild to moderate and self-limiting. Patients with previous pneumonia or other risk factors for pulmonary infections such as chronic obstructive lung disease seem to show a slightly increased risk of developing infectious complications of the bronchopulmonary system while being on anakinra and should be monitored appropriately. Combining IL-1ra treatment with the use of anti-TNF agents showed an increased risk of infectious complications in clinical studies and is not recommended at present. Studies are currently assessing the use of anakinra for treatment of other rheumatic diseases like psoriatic arthritis, juvenile arthritis or spondylarthropathy.

Paeoniflorin suppresses inflammatory mediator production and regulates G protein-coupled signaling in fibroblast – like synoviocytes of collagen induced arthritic rats

“…FLS secrete inflammatory cytokines (IL-1 beta and TNFalpha) and inflammatory mediators (PGE 2 and MMPs). These products play a crucial role in induction of synovitis, pannus, cartilage destruction and bone erosion in the process of RA [18]. In RA patients, the concentration of IL-1 in synovial fluid increased [19].…”

LIGHT is involved in the pathogenesis of rheumatoid arthritis by inducing the expression of pro‐inflammatory cytokines and MMP‐9 in macrophages

“…Some of the pro‐inflammatory cytokines also have the capacity to modulate cartilage and bone metabolism 29 . IL‐1 and TNF‐α are the most well studied cytokines in RA and the importance of these cytokines has been demonstrated by clinical effectiveness of the IL‐1 receptor antagonist and neutralizing antibodies directed against TNF‐α 30–32 . TNF‐α triggers both local and systemic inflammation whereas IL‐1 is involved at the local cartilage and bone destruction.…”

“…29 IL-1 and TNF-a are the most well studied cytokines in RA and the importance of these cytokines has been demonstrated by clinical effectiveness of the IL-1 receptor antagonist and neutralizing antibodies directed against TNF-a. [30][31][32] TNF-a triggers both local and systemic inflammation whereas IL-1 is involved at the local cartilage and bone destruction. IL-1 and TNF-a strongly synergize in numerous biological functions as well.…”

Effects of an acetone extract of Boswellia carterii Birdw. (Burseraceae) gum resin on adjuvant-induced arthritis in lewis rats

“…Such therapies are helpful in controlling the symptoms of acute RA, but their effects on chronic, prolonged RA are unsatisfactory. Moreover, the adverse effects of drug therapy are significant and include gastrointestinal disturbances, infections and cardiovascular risks (Scheiman, 2001;Mangge et al, 2003;Rubbert-Roth and Perniok, 2003;Ortiz, 2004). The inflammatory process of RA is reportedly associated with an increase of the pro-inflammatory cytokines TNF-␣ and IL-1␤ (Dayer, 2003;Fleischmann et al, 2004;Shin et al, 2003).…”