Anti-cytokine therapy in rheumatoid arthritis.
The past few years have seen an explosion of knowledge concerning the role of cytokines and their naturally occurring inhibitors in the promotion and modulation of inflammatory disease. In RA, this knowledge has been translated into the clinic, with ongoing evaluation of specific cytokine inhibitors, including those targeting tumour necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1) and interleukin-6 (IL-6). In this review, we outline the scientific data supporting anti-cytokine therapies in RA and describe the results of published and unpublished clinical trials with biological agents. At least for anti-TNF therapy, short-term clinical efficacy and good tolerability have been confirmed in randomized, placebo controlled trials. The results of IL-1 blockade in vivo also appear encouraging, although detailed descriptions of trail outcomes are awaited. Problems associated with long-term administration of biological agents are discussed, including the development of antiglobulin responses to injected monoclonal antibodies and poor pharmacokinetics of low-molecular-weight inhibitors. Ways of facilitating the long-term use of current biological agents and alternative means for inhibiting cytokine function in future studies in RA are presented.
Elliott
M J
MJ
Charing Cross Hospital, London, UK.
Maini
R N
RN
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000628:therapy*; D002986:Clinical Trials as Topic; D006801:Humans; D007167:Immunotherapy; D007375:Interleukin-1 / Q000037:antagonists & inhibitors*; D016032:Randomized Controlled Trials as Topic; D017472:Receptors, Interleukin-1 / Q000502:physiology; D011994:Recombinant Proteins; D012995:Solubility; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D000093242:Interleukin-6 Inhibitors
D000911:Antibodies, Monoclonal; D007375:Interleukin-1; D017472:Receptors, Interleukin-1; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D000093242:Interleukin-6 Inhibitors