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

Phase 2
Not Enrolling
Inflammation, Vasculitis, Wegener's Granulomatosis

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Trial Information

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.

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

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.


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).

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Primary Purpose: Treatment


United States: Federal Government

Study ID:




Start Date:

March 1990

Completion Date:

February 2004

Related Keywords:

  • Inflammation
  • Vasculitis
  • Wegener's Granulomatosis
  • Vasculitis
  • Cytotoxic Therapy
  • Inflammation
  • Glomerulonephritis
  • Inflammatory Sinusitis
  • Inflammation
  • Vasculitis
  • Wegener Granulomatosis
  • Systemic Vasculitis



National Institute of Allergy and Infectious Diseases (NIAID) Bethesda, Maryland  20892