Advances in the therapy of Wegener's granulomatosis.
OBJECTIVE
In the past, recommendations for the treatment of Wegener's granulomatosis were primarily based on findings reported from open-label clinical trials. Results from several randomized controlled trials in patients with Wegener's granulomatosis and other antineutrophil cytoplasm antibody-associated vasculitides have recently been reported that have a great impact on patient care.


RESULTS
In view of the considerable toxicity of cyclophosphamide, strategies to limit exposure to it have recently been evaluated. The replacement of cyclophosphamide by azathioprine after the successful induction of remission has been demonstrated not to increase the rate of relapse compared with continued cyclophosphamide. In patients with early antineutrophil cytoplasm antibody-associated vasculitides without critical organ manifestations low-dose methotrexate can replace cyclophosphamide for induction treatment with similar remission rates. As the early discontinuation of immunosuppressive treatment is associated with unacceptably high relapse rates, however, treatment for the maintenance of remission is mandatory. Besides azathioprine, leflunomide and methotrexate were efficacious in preventing relapses in Wegener's granulomatosis. Data on anti-cytokine therapy in Wegener's granulomatosis are controversial, possibly related to differences in study design. Open-label clinical studies suggest a beneficial effect of infliximab in addition to standard therapy in refractory Wegener's granulomatosis. In contrast, a recent randomized controlled trial showed that etanercept in addition to standard therapy, with the subsequent tapering of standard medications, is not effective for the maintenance of remission.


CONCLUSIONS
Despite recent progress, the prevention of relapses and treatment of refractory cases remain the greatest challenges in the treatment of Wegener's granulomatosis.
Hellmich
Bernhard
B
Department of Rheumatology, University Hospital of Schleswig-Holstein, Campus Luebeck and Rheumaklinik Bad Bramstedt, Luebeck, Germany. hellmich@rheuma-zentrum.de
Lamprecht
Peter
P
Gross
Wolfgang L
WL
D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D058846:Antibodies, Monoclonal, Murine-Derived; D001379:Azathioprine / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000627:therapeutic use; D000068800:Etanercept; D014890:Granulomatosis with Polyangiitis / Q000188:drug therapy* / Q000628:therapy; D006146:Guanidines / Q000627:therapeutic use; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007555:Isoxazoles / Q000627:therapeutic use; D000077339:Leflunomide; D008727:Methotrexate / Q000627:therapeutic use; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D010956:Plasmapheresis; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use; D012008:Recurrence; D000069283:Rituximab
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D006146:Guanidines; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D007555:Isoxazoles; D018124:Receptors, Tumor Necrosis Factor; D000069283:Rituximab; C033797:spergualin; D003520:Cyclophosphamide; D000077339:Leflunomide; D009173:Mycophenolic Acid; D001379:Azathioprine; D000068800:Etanercept; D008727:Methotrexate