TNF inhibition as therapy for rheumatoid arthritis.
The introduction of TNF- alpha -inhibiting biologicals has been a major therapeutic breakthrough in rheumatoid arthritis therapy. Against a background of conventional disease-modifying antirheumatic drug experience, this review focuses on present experiences and possible future developments. TNF inhibition results in profound improvement in the majority of rheumatoid arthritis patients, but non-response and adverse effects need attention. Adalimumab is being filed for approval. Other monoclonal antibodies or receptor constructs are in late development. Small molecule inhibitors of TNF production or signalling are a hot topic. One emerging target is nuclear factor kappa B and selective inhibition has proved effective in animal models of arthritis. Synovial proliferation in rheumatoid arthritis is characterised by diminished apoptosis of fibroblasts, whereas bone marrow precursor cells undergo accelerated apoptosis in active rheumatoid arthritis. Both abnormalities are seemingly ameliorated by TNF inhibition. Anti-apoptotic strategies will soon go into development for control of unresponsive rheumatoid arthritis.
Wollheim
Frank A
FA
Department of Rheumatology, Lund University Hospital, SE221 85 Lund, Sweden. Frank.Wollheim@reum.lUSe
D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D006801:Humans; D016899:Interferon-beta / Q000627:therapeutic use; D007378:Interleukins / Q000037:antagonists & inhibitors; D017211:Treatment Failure; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000627:therapeutic use*
D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D007378:Interleukins; D014409:Tumor Necrosis Factor-alpha; D016899:Interferon-beta