New approaches to treatment in systemic vasculitis: biological therapies.
Although the effectiveness of biological agents in systemic vasculitis is unproven, their introduction heralds a new era of vasculitis treatment. These agents offer the promise of targeted immunotherapies; the possibility of greater efficacy (and fewer side-effects) than conventional vasculitis treatments; and the potential to provide novel insights into the pathophysiology of these diseases-insights that may be gained only by using these agents in humans. Challenges to the investigation of these therapies in the systemic vasculitides exist, but important basic and clinical investigations are already in progress. We review the major issues facing the investigation of biological agents in vasculitis; examine the rationale for believing that biological strategies in vasculitis will be efficacious; identify several candidate targets for biological approaches; and discuss the results to date of early studies. The potential biological targets discussed include cytokines such as tumour necrosis factor; interleukins-1, -6, and -12; interferon-gamma; the co-stimulatory molecules B7-1 and B7-2; and others.
Levine
S M
SM
Division of Rheumatology and Department of Medicine, The Johns Hopkins Vasculitis Center, Baltimore, MD 21205, USA.
Stone
J H
JH
D000069594:Abatacept; D000818:Animals; D015703:Antigens, CD / Q000627:therapeutic use; D000943:Antigens, Differentiation / Q000627:therapeutic use; D018122:B7-1 Antigen / Q000627:therapeutic use; D051940:B7-2 Antigen; D001688:Biological Products / Q000627:therapeutic use*; D060908:CTLA-4 Antigen; D016207:Cytokines / Q000627:therapeutic use; D000068800:Etanercept; D014890:Granulomatosis with Polyangiitis / Q000628:therapy; D006801:Humans; D018796:Immunoconjugates; D007074:Immunoglobulin G / Q000627:therapeutic use; D007167:Immunotherapy; D007371:Interferon-gamma / Q000627:therapeutic use; D007378:Interleukins / Q000627:therapeutic use; D008562:Membrane Glycoproteins / Q000627:therapeutic use; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use; D014657:Vasculitis / Q000276:immunology / Q000628:therapy*
D015703:Antigens, CD; D000943:Antigens, Differentiation; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D001688:Biological Products; C497964:CD86 protein, human; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D016207:Cytokines; D018796:Immunoconjugates; D007074:Immunoglobulin G; D007378:Interleukins; D008562:Membrane Glycoproteins; D018124:Receptors, Tumor Necrosis Factor; D000069594:Abatacept; D007371:Interferon-gamma; D000068800:Etanercept