Use of a cyclophosphamide-induction methotrexate-maintenance regimen for the treatment of Wegener's granulomatosis: extended follow-up and rate of relapse.
OBJECTIVE
To determine the relapse rate and outcome in patients with Wegener's granulomatosis treated with daily cyclophosphamide and glucocorticoids to induce remission followed by methotrexate for remission maintenance.


METHODS
We performed an open-label prospective study in 42 patients with active Wegener's granulomatosis. All patients were treated with a standardized regimen. Outcomes were assessed using predetermined definitions based on clinical characteristics and pathologic, laboratory, and radiographic findings.


RESULTS
All patients achieved disease remission. The median time to remission was 3 months, and the median time to discontinuation of glucocorticoids was 8 months. During a median of 32 months of follow-up, 1 patient died (of a myocardial infarction not related to vasculitis). Two patients (5%) had to withdraw from the study because of medication toxicity. Twenty-two patients (52%) relapsed, with glomerulonephritis occurring in 16 patients. Of these 16 patients, 4 had an increase of >0.2 mg/dL in serum creatinine level. All 4 patients returned to their prior level of renal function with treatment. None of the 22 relapses met the criteria for severe disease.


CONCLUSIONS
The use of cyclophosphamide and glucocorticoids for induction and methotrexate for maintaining remission is an effective and well-tolerated therapeutic approach in patients with active Wegener's granulomatosis.
Langford
Carol A
CA
National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. clangford@niaid.nih.gov
Talar-Williams
Cheryl
C
Barron
Karyl S
KS
Sneller
Michael C
MC
D000293:Adolescent; D000328:Adult; D000368:Aged; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000032:analysis; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000627:therapeutic use*; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D003520:Cyclophosphamide / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D005938:Glucocorticoids / Q000627:therapeutic use; D014890:Granulomatosis with Polyangiitis / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000009:adverse effects / Q000627:therapeutic use*; D011241:Prednisone / Q000627:therapeutic use; D011446:Prospective Studies; D012008:Recurrence; D012074:Remission Induction
D019268:Antibodies, Antineutrophil Cytoplasmic; D000964:Antimetabolites, Antineoplastic; D018906:Antineoplastic Agents, Alkylating; D005938:Glucocorticoids; D003520:Cyclophosphamide; D011241:Prednisone; D008727:Methotrexate