Frentizole Therapy of Active Systemic lupus Erythematosus

Abstract

Frentizole is a benzimidazoleurea that has immunosuppressive properties in mice. Eleven steroid-treated patients with active systemic lupus erythematosus received frentizole (150-350 mg/day) in combination with stable or decreasing doses of prednisone in an open label trial. Nine patients completed at least one 21-to 75-day course of therapy with this drug. Clinical parameters of disease improved in 8 of these 9 patients. Mean DNA binding decreased by 28%, mean CH50 increased by 20%, and mean absolute lymphocyte and T cell counts decreased by 25-2696. Granulocytopenia was not observed. Three patients developed reversible hepatic toxicity. Clinical and serologic improvement was noted in 3 patients who accepted a second W a y course of frentizole therapy. tive to cytotoxic antineoplastic agents which are used to treat selected autoimmune diseases (1). This drug was selected for testing in humans after initial screening showed that it had immunosuppressive properties in mice (24). In the NZB/NZW mouse model of systemic lupus erythematosus (SLE), therapy with frentizole prolonged life and decreased proteinuria (43). Frentizole had a therapeutic index 3 to 7 times greater than cytotoxic antineoplastic drugs and was synergistic with cortisone (43). When frentizole was given to mice in a dose greater than the amount needed to cause immunosuppression, the incidence of infection was not increased (6). In experimental animals, therapy with frentizole was associated with anemia, hepatic toxicity, and thyroid toxicity after large doses were given over an extended period of time (5,7). The effectiveness of this drug as an immunosuppressive agent and its relatively low toxicity in animals prompted us to design a trial to determine if frentizole had immunosuppressive and/or toxic effects in patients with SLE. PATIENTS AND METHODSEleven adult SLE patients were enrolled in the trial (Table 1). Each patient met the five predetermined selection criteria outlined in Table 2. Patients with one or more of the following findings were excluded: central nervous system lupus; lupus pneumonitis; infection; pregnancy or lactation; earlier cytotoxic drug therapy; uncompensated hemolytic anemia; hematocrit less than 26% or hemoglobin less than 9 gm/ 100 ml; platelet count less than 80,000/mm3; serum creatinine greater than 3 mg/100 ml; blood urea nitrogen greater than 40 mg/100 ml; creatinine clearance less than 50 ml/minUte.Three protocols were utilized in this trial. In each protocol, patients were maintained on previous doses of prednisone, and frentizole was added in a single daily dose for a predetermined length of time. Other concomitantly administered

Effects of Prolactin in Stimulating Disease Activity in Systemic Lupus Erythematosusa

“…The seven remaining patients were 26 to 48 years old and satisfied at least four of the 1982 revised American Rheumatism Association Criteria for the Classification of SLE. 82 Entry guidelines were patterned after those described in an earlier publication 83 and excluded patients with rapidly progressive disease or life‐threatening complications of SLE. Four of the seven study patients were taking stable doses of prednisone at entry (mean dose = 10 mg per day).…”