A pilot study of zileuton, a novel selective 5-lipoxygenase inhibitor, in patients with systemic lupus erythematosus.
OBJECTIVE
This is a pilot study of zileuton, a selective 5-lipoxygenase inhibitor in systemic lupus erythematosus (SLE).


METHODS
Forty patients with SLE received zileuton 600 mg qid or placebo in an 8 week, randomized prospective, double blind trial. Disease activity was manifested largely by constitutional, articular, and skin manifestations with no evidence of active renal, cardiac, or neurologic involvement. Concomitant administration of nonsteroidal antiinflammatories, corticosteroids, or antimalarials was not permitted. Disease activity was determined at baseline and at Days 15 and 57 by assessment of arthritis severity, the Systemic Lupus Activity Measure (SLAM), investigator and patient global ratings, hematologic indices, and serologic measures including autoantibody titers, complement levels, and interleukin 2 receptors (IL-2R). Total body sulfidopeptide leukotriene synthesis was measured by urinary leukotriene E4 (LTE4) concentrations.


RESULTS
Overall SLAM (the primary measure of efficacy in this study) was significantly improved with zileuton compared with placebo (-2.1 +/- 1.3, compared with an increase of 2.3 +/- 1.3 with placebo by Day 57, p = 0.048). Changes in individual SLAM subscores, arthritis severity, global ratings, and IL-2R levels compared with baseline did not achieve statistical significance, but were generally decreased from baseline with zileuton (indicating trends towards improvement) and increased from baseline with placebo (indicating trends towards clinical worsening). Urine LTE4 levels at Day 57 had increased from baseline in the placebo group (indicating worsening) and decreased in the zileuton group (indicating improvement).


CONCLUSIONS
Selective 5-lipoxygenase inhibition may be beneficial in mild SLE.
Hackshaw
K V
KV
Department of Medicine, Ohio State University, Columbus, Columbus 43210-1228, USA.
Shi
Y
Y
Brandwein
S R
SR
Jones
K
K
Westcott
J Y
JY
D000328:Adult; D000368:Aged; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006918:Hydroxyurea / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D020024:Leukotriene Antagonists; D017999:Leukotriene E4 / Q000652:urine; D016859:Lipoxygenase Inhibitors; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies; D016896:Treatment Outcome
D020024:Leukotriene Antagonists; D016859:Lipoxygenase Inhibitors; D017999:Leukotriene E4; C063449:zileuton; D006918:Hydroxyurea