An Open Trial of the Efficacy of Glucocorticoids and Methotrexate (MTX) in the Treatment of Systemic Vasculitis

Study start date: March 1, 1990

INCLUSION CRITERIA: Diagnosis: Wegener's granulomatosis. Age: 10-80 years. Qualifications to eligibility: Prior documentation of vasculitis based on clinical characteristics and histopathological and/or angiographic evidence of vasculitis. Patients will be eligible for this study regardless of whether they are currently receiving immunosuppressive therapies. Failure to respond to prior therapy with other cytotoxic agents or toxicity from such agents, in the setting of persistent disease, will constitute one reason for eligibility for this study. In the absence of histopathological and/or angiographic evidence of vasculitis, patients with the following criteria will also be eligible: A. Positive C-ANCA (done at the NIH), and B. Glomerulonephritis as evidenced by the presence of red blood cell casts and proteinuria or renal biopsy showing necrotizing glomerulonephritis in the absence of positive immunofluorescence for immunoglobulin and complement, and C. One or more of the following: Inflammatory sinusitis with histopathological evidence of granulomatous inflammation and negative special stains for mycobacteria and fungi. Sinusitis must be present for at least 3 months and have failed to respond to at least 2 weeks of antibiotic therapy directed against likely pathogens (H. influenza, S. pneumonia, and upper respiratory tract anaerobic bacteria); Pulmonary nodule or infiltrates in a patient in the absence of infection. Evidence of active disease as defined by a Vasculitis Disease Activity Index of greater than or equal to 3 (Appendix I) or if begun on immunosuppressive therapy at an outside institution, a history of a Vasculitis Disease Activity Index greater than or equal to 3 during the past 6 months. EXCLUSION CRITERIA: Evidence of infection by gram stain and/or culture specimens. In those instances in which infection cannot be ruled out by gram stain and culture of secretions or collections of fluid in involved organs, it may be necessary to obtain a biopsy of the affected tissue for microbiological and histopathological studies. Recent (within four weeks) increase in GC or cytotoxic drug therapy. Patients who are pregnant or nursing infants will not be eligible. Fertile women should have a negative pregnancy test within one week prior to study entry and should be using effective means of birth control. Processes that would predispose to enhanced risk of MTX toxicity: acute or chronic liver disease, alcohol abuse (greater than 14 oz of 100 proof liquor or equivalent per week), active peptic ulcer disease, and inability to comply with study guidelines. Serological evidence of infection with human immunodeficiency virus (a serological determination will be performed within two weeks of study entry).