Phase II Randomized Study of Glucocorticoids With or Without Methotrexate for Treatment of Giant Cell Arteritis
Phase II Randomized Study of Glucocorticoids With or Without Methotrexate for Treatment of Giant Cell Arteritis
OBJECTIVES: I. Compare the long term outcomes in patients with giant cell arteritis after
 glucocorticoid treatment with or without methotrexate.

 II. Compare remission relapse rates in these patients after glucocorticoid therapy with or
 without methotrexate.

 III. Determine whether adjunctive use of methotrexate lowers cumulative dose and duration of
 glucocorticoid therapy and whether there is less treatment related morbidity and mortality.

 IV. Demonstrate the feasibility of long term, double blind, placebo controlled, randomized,
 multicenter trials for treatment of systemic vasculitides.
PROTOCOL OUTLINE: This is a randomized, double blind, multicenter study. Patients are
 randomized into initial therapy with prednisone plus weekly placebo or prednisone plus weekly
 oral methotrexate. Patients who do not respond to treatment within 5 days are taken off
 study. If methotrexate toxicity dose not occur after 2 weeks, methotrexate is increased by
 one tablet per week until a maximum tolerated dose (MTD) is achieved. The MTD of methotrexate
 or the matching placebo dose is continued for 12 months in the absence of toxicity. Once 12
 continuous months of remission are achieved, methotrexate or placebo is tapered to
 discontinuation.

 Patients are followed for 1-6 years.

 Completion date provided represents the completion date of the grant per OOPD records
PROTOCOL ENTRY CRITERIA:

 --Disease Characteristics--

 Diagnosis of giant cell arteritis (GCA) by at least one of the following:

 -  Temporal artery biopsy confirming GCA Symptoms of GCA (including new onset (within 6
 months) symptoms of headaches, tenderness of the scalp or the temporal arteries,
 visual loss due to retinal ischemic optic neuropathy or otherwise unexplained tongue
 or jaw pain) and an aortic angiogram that revealed stenotic and/or aneurysmal disease
 of the aorta and its principal branches

 -  Symptoms of polymyalgia rheumatica plus ischemic optic neuropathy, newly identified
 tenderness over a temporal artery, or new onset of tongue or jaw pain

 Westergren erythrocyte sedimentation rate of at least 40 nm in one hour

 --Prior/Concurrent Therapy--

 Endocrine therapy: No greater than 20 days since initiation of prednisone therapy

 Other: No concurrent sulfa drugs or nonsteroidal antiinflammatory drugs

 --Patient Characteristics--

 Hematopoietic:

 -  WBC at least 4,000/mm3

 -  Platelet count at least 120,000/mm3

 -  No acute or chronic liver disease

 Hepatic:

 -  Alkaline phosphatase no greater than 2 times upper limit of normal

 -  No other reproducible abnormal liver function test

 Renal: Creatinine less than 2.0 mg/dL

 Other:

 -  HIV negative

 -  No symptomatic peptic ulcer disease within the last 3 months

 -  Hepatitis B or C antigen negative

 -  No alcohol use in excess of 2 ounces of 100 proof liquor or 1 beer or its equivalent
 per week

 -  No insulin dependent diabetes mellitus plus morbid obesity (greater than 33% over
 ideal body weight)

 -  No recently (less than 6 months) diagnosed malignancy

 -  Not pregnant or nursing

 -  Adequate contraception required of all fertile patients