The treatment of wegener's granulomatosis with glucocorticoids and methotrexate

Abstract

Objective. To identify alternatives to daily low‐dose cyclophosphamide (CYC) in the treatment of Wegener's granulomatosis (WG).Methods. An open‐label pilot study of weekly low‐dose methotrexate (MTX) plus glucocorticoids (GC) for treatment of patients with WG was performed. Twenty‐nine patients who did not have immediately life‐threatening disease were included. Outcome was determined by clinical characteristics, pathologic findings, course of illness, laboratory and radiographic findings, and successful withdrawal of GC therapy.Results. Weekly administration of MTX (at a mean stable dosage of 20 mg) and GC resulted in marked improvement in 76% of the 29 patients. Remission was achieved in 69% of the patients, 7% improved but had intermittent smoldering disease that precluded total withdrawal of GC, and 17% had progressive disease within 2–6 months of starting the study treatment. Two patients who initially achieved remission later had relapses after GC was discontinued. Of those who remain in remission (mean followup time 14.5 months), 72% have not required GC for a mean period of 10 months.Conclusion. Although standard therapy for WG (daily CYC and GC) has dramatically improved outcome in this often‐fatal disease, treatment morbidity has led to attempts to identify effective interventions that have less toxicity. Weekly low‐dose MTX was shown in this study to be a feasible alternative to CYC in patients whose illness was not immediately life‐threatening or in whom prior CYC treatment was ineffective or produced serious toxicity. Although these results are preliminary, they are encouraging and justify further studies in which MTX, CYC, and other alternative therapeutic approaches are compared concurrently.

A serum proteomic approach to gauging the state of remission in Wegener's granulomatosis

“…In the BVAS/WG, disease remission is defined as a score of 0, signifying the absence of any new, worse, or persistent symptoms or signs of active disease. In the interest of uniformity with regard to treatment, we selected only patients with severe disease (defined as WG that posed an immediate threat either to the patient's life or to the function of a vital organ [1,11,12,[14][15][16]) and patients who, by virtue of multiorgan system disease, were at risk for the above-defined severe disease.…”

“…Wegener's granulomatosis (WG), one of the most common forms of systemic vasculitis, is the prototype of disorders associated with antineutrophil cytoplasmic antibodies (ANCAs) (1,2). At least 90% of patients with WG sustain permanent morbidity from the disease, including renal failure, pulmonary dysfunction, hearing loss, visual impairment, and chronic sinus problems (1)(2)(3).…”

“…At least 90% of patients with WG sustain permanent morbidity from the disease, including renal failure, pulmonary dysfunction, hearing loss, visual impairment, and chronic sinus problems (1)(2)(3). Conventional therapies for WG consist of glucocorticoids and cytotoxic agents such as cyclophosphamide.…”

“…Conventional therapies for WG consist of glucocorticoids and cytotoxic agents such as cyclophosphamide. Complications of these treatment regimens are common and often devastating: in one longitudinal series, 42% of patients experienced permanent morbidity related to treatment (1). Treatmentassociated toxic effects include bone marrow hypoplasia, an increased risk of malignancies (leukemia, lymphoma, bladder cancer), infertility, obesity, osteoporosis, hypertension, diabetes, and opportunistic infections.…”

“…Treatmentassociated toxic effects include bone marrow hypoplasia, an increased risk of malignancies (leukemia, lymphoma, bladder cancer), infertility, obesity, osteoporosis, hypertension, diabetes, and opportunistic infections. Moreover, despite the currently available therapies, between 50% and 80% of patients experience disease flares after the achievement of remission (1,2,4).…”