[New biological therapeutic options for the treatment of RE: inhibition of costimulatory molecules and blockade of Interleukin-6-interaction].
After approval of TNF and interleukin-1 inhibiting agents for treatment of refractory rheumathoid arthritis, new agents inhibiting interleukin-6 and costimulatory pathways are entering clinical phase I and II trials. Blockade of costimulation by using a CTLA4 immunoglobulin fusion protein (CTLA4Ig), which inhibits the interaction between CD 28 and CD80/86, has been studied in humans and was demonstrated to be well tolerated and efficacious. A monoclonal antibody to the IL-6 receptor (MRA) blocks bioactivity of IL-6 and also showed favorable effects in first clinical trials. Drug safety data on both substances revealed no severe toxicity or increased incidence of severe infections. For the first time combinations of biological substances like CTLA4Ig and etanercept were demonstrated to be effective and showed no evidence for an increased rate of severe infectious complications. Encouraged by data on these two agents there is substancial hope for a broadened therapeutic armentarium of biological agents in refractory rheumatoid arthritis.
Klinikum der Universität zu Köln, Klinik und Poliklinik für Innere Medizin II, Joseph-Stelzmann-Strasse 9, 50931 Köln, Germany. a.perniok@uni-koeln.de
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Rubbert-Roth
D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000009:adverse effects / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology; D060908:CTLA-4 Antigen; D002986:Clinical Trials as Topic; D015507:Drugs, Investigational / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use; D007375:Interleukin-1 / Q000037:antagonists & inhibitors; D011993:Recombinant Fusion Proteins / Q000009:adverse effects / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors; D000093242:Interleukin-6 Inhibitors
D015703:Antigens, CD; D000943:Antigens, Differentiation; D018501:Antirheumatic Agents; D060908:CTLA-4 Antigen; D015507:Drugs, Investigational; D007166:Immunosuppressive Agents; D007375:Interleukin-1; D011993:Recombinant Fusion Proteins; D014409:Tumor Necrosis Factor-alpha; D000093242:Interleukin-6 Inhibitors; C556706:CTLA4 protein, human