An Open Trial of the Efficacy of Glucocorticoids and Methotrexate (MTX) in the Treatment of Systemic Vasculitis
Previous studies at the NIH have demonstrated that in over 90% of cases of Wegener's
granulomatosis (WG) and other systemic necrotizing vasculitides, glucocorticoid (GC) and
daily low dose cyclophosphamide (CP) therapy has resulted in marked improvement and even
remission. However, such therapy has been associated with about 50% relapses, 10%
resistance to initial treatment and significant toxicity in almost all patients.
Consequently, we have attempted to identify alternative therapies for the systemic
vasculitides that would be less toxic then daily CP. An NIH study of the efficacy of
intermittent high dose intravenous CP and daily GC (Protocol #88-I-56) revealed that 79% of
14 patients with WG either failed to respond to treatment, did not sustain improvement or
could not tolerate continued treatment during a period of approximately two years. In
another study (Protocol #89-I-18), we evaluated treatment with GC and weekly oral doses of
methotrexate (MTX) in 15 patients with Takayasu's arteritis, in whom disease previously
failed to be controlled with GC, GC + CP, or in whom remission with such treatment was
followed by relapse. Fifty-three percent (8/15) of patients previously dependent on GC were
able to achieve remission and discontinue GC therapy. Five of seven patients who remained
on GC were in remission and receiving at least 50% less GC than prior to MTX therapy. Only
three patients had progressive disease. The mean follow-up period was 20 months. We have
also recently analyzed our results for MTX + GC therapy and 29 patients with WG.
Seventy-six percent of patients had marked improvement and 69% achieved remission.
Seventy-two percent of those in remission have not required GC therapy for a mean period 10
months. We conclude that weekly low dose MTX therapy is a feasible alternative to CP in the
treatment of systemic vasculitis. Judgement of the ultimate value of such therapy should be
deferred until a greater number of patients have been studied over a longer period of time.
Endpoint Classification: Safety/Efficacy Study, Primary Purpose: Treatment
United States: Federal Government
|National Institute of Allergy and Infectious Diseases (NIAID)||Bethesda, Maryland 20892|