Phase I/II Trial of TNFR:Fc (Etanercept) in Patients With Wegener's Granulomatosis

This study will examine the use of etanercept (also called Enbrel or TNFR:Fc) in patients with Wegener's granulomatosis, a type of vasculitis (blood vessel inflammation). Wegener's granulomatosis may affect many parts of the body, including the brain, nerves, eyes, sinuses, lungs, kidneys, intestinal tract, skin, joints, heart, and other sites. Generally, the greater the disease involvement, the more life-threatening it is. Standard treatment is a combination of prednisone and a cytotoxic agent-usually cyclophosphamide or methotrexate. However, many patients treated with this regimen have a disease relapse, and others cannot take these drugs because of severe side effects. This study will evaluate etanercept's safety and effectiveness, and particularly its value in reducing the need for prednisone and preventing disease relapse.

The Food and Drug Administration has approved etanercept for treating rheumatoid arthritis, another inflammatory disease. The drug works by blocking the activity of TNF-a protein made by white blood cells that is involved in the inflammatory process. Since prednisone also affects inflammatory proteins and lowers TNF production, the use of etanercept may reduce the need for prednisone in patients with Wegener's granulomatosis, and thus the risk of its side effects.

Patients between 10 and 70 years of age with Wegener's granulomatosis who have never taken prednisone, methotrexate or cyclophosphamide, or have taken these drugs for less than 3 weeks may be eligible for this study.

Participants will have a medical history review and physical examination, including laboratory studies. If medically indicated, X-rays, consultations and biopsies (surgical removal of a small tissue sample) of affected organs will also be done. All patients will begin treatment with prednisone, methotrexate and etanercept. Those who improve on this regimen will stop prednisone gradually over 3 months. Those who achieve disease remission at the end of another 3 months will be randomly assigned to either continue taking etanercept and methotrexate for another 12 months or to stop etanercept and continue only methotrexate for the next 12 months (after which methotrexate will gradually be stopped). Patients who are not in remission by the 6-month point will continue taking etanercept until they go into remission, when they will be assigned to stop or not stop etanercept, as described above. Patients who do not achieve remission within 12 months of beginning treatment will be taken off the study. Patients who have a disease relapse while on the study will likely be switched to treatment with prednisone and either methotrexate or cyclophosphamide. Patients randomized to stop etanercept and who have a relapse within a year of stopping the drug may be offered re-treatment on this protocol, but with continuing etanercept for a full year after remission.

Patients will be evaluated in the outpatient clinic every 2 to 4 weeks for the first 4 months and every 1 to 3 months after that. Patients whose disease is in remission and who stop all medications will be followed every 3 to 6 months for 2 years. Follow-up evaluations include a physical examination, blood draws and, if medically indicated, X-rays. The total study duration is 60 to 70 months.