New indications for treatment of chronic inflammation by TNF-alpha blockade.
The impressive anti-inflammatory effects of the tumor necrosis factor (TNF)alpha blockers etanercept and infliximab have led to their use in multiple inflammatory diseases besides their original indication, rheumatoid arthritis (RA). The well-studied clinical effects of both agents in RA are the reduction of signs and symptoms of joint inflammation as well as the arrest of bone destruction. Infliximab has also been Food and Drug Administration-approved in the treatment of Crohn disease; etanercept is now FDA-approved for juvenile chronic arthritis and psoriatic arthritis. Favorable initial clinical trials have been reported in other rheumatic diseases, including ankylosing spondylitis and adult Still disease. In addition, TNF alpha blockade is being studied in the treatment of uveitis, myelodysplastic syndromes, and graft-versus-host disease. Studies in sepsis and septic shock have identified small subsets of patients that may benefit from TNF alpha blockade, but broader use in septic patients has not improved survival. The TNF alpha blockers have had relatively infrequent serious side effects, especially compared with the immunosuppressive and cytotoxic agents otherwise employed to treat these diseases. Further studies of optimal dosing, combination with other therapies, and long-term benefits and side effects will emerge from future trials.
Reimold
Andreas M
AM
Rheumatic Diseases Division, University of Texas Southwestern Medical Center, Dallas 75390, USA. andreas.reimold@utsouthwestern.edu
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000276:immunology; D002986:Clinical Trials as Topic; D003424:Crohn Disease / Q000188:drug therapy / Q000276:immunology; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D000068800:Etanercept; D006086:Graft vs Host Disease / Q000188:drug therapy / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000276:immunology / Q000627:therapeutic use*; D007249:Inflammation / Q000188:drug therapy* / Q000276:immunology*; D000069285:Infliximab; D051379:Mice; D009190:Myelodysplastic Syndromes / Q000188:drug therapy / Q000276:immunology; D011565:Psoriasis / Q000188:drug therapy / Q000276:immunology; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use; D018805:Sepsis / Q000188:drug therapy / Q000276:immunology; D013167:Spondylitis, Ankylosing / Q000188:drug therapy / Q000276:immunology; D016706:Still's Disease, Adult-Onset / Q000188:drug therapy / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D014481:United States; D014486:United States Food and Drug Administration; D014605:Uveitis / Q000188:drug therapy / Q000276:immunology
D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D016207:Cytokines; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068800:Etanercept