Effects of prasterone on corticosteroid requirements of women with systemic lupus erythematosus: A double‐blind, randomized, placebo‐controlled trial

Abstract

Objective. To evaluate whether treatment with prasterone (dehydroepiandrosterone [DHEA]) would allow the dosage of prednisone (or an equivalent corticosteroid) to be reduced to <7.5 mg/day for 2 months or longer while maintaining stable or reduced disease activity in steroid-dependent women with systemic lupus erythematosus (SLE).Methods. In a double-blind, randomized trial, 191 female SLE patients receiving prednisone (10-30 mg/ day) were treated daily with either placebo, 100 mg of oral prasterone (an adrenal androgen), or 200 mg of oral prasterone for 7-9-months. At monthly intervals, corticosteroid dosages were reduced by algorithm in patients whose SLE Disease Activity Index (SLEDAI) score was stable or improved. Patients for whom a sustained reduction in the dosage of prednisone (<7.5 mg/day) was achieved for at least the last 2 months of the 7-9-month treatment period were classified as responders.Results. Response rates were 41% in the placebo group, 44% in the 100-mg prasterone group, and 55% in the 200-mg group (P ‫؍‬ 0.110, 200 mg versus placebo). Among the 137 subjects (45 in the placebo group, 47 in the 100-mg group, and 45 in the 200-mg group) who had active disease at baseline (defined as SLEDAI score >2), 29%, 38%, and 51%, respectively, were responders (P ‫؍‬ 0.031 for 200 mg prasterone versus placebo). Acne was the most common adverse event but was generally mild. Clinical and laboratory changes primarily reflected androgenic effects of prasterone.Conclusion. Among women with lupus disease activity, reducing the dosage of prednisone to <7.5 mg/day for a sustained period of time while maintaining stabilization or a reduction of disease activity was possible in a significantly greater proportion of patients treated with oral prasterone, 200 mg once daily, compared with patients treated with placebo.Systemic lupus erythematosus (SLE) is a chronic, autoimmune, inflammatory disease of unknown etiology. After puberty, SLE is more common in women than in men, with a ratio of 9:1 (1). Abnormalities of both estrogen and androgen metabolism have been described in SLE patients, including enhanced formation of 16-␣ hydroxyestrone, an active metabolite of estradiol (2,3), and depressed blood androgen concentrations (4). Androgen treatment induces a delay in the appearance of anti-DNA antibodies and the onset of nephritis and decreases mortality in female (NZB ϫ NZW)F 1 hybrid mice, a well-characterized animal model of SLE (5-7).

Dehydroepiandrosterone treatment of women with mild‐to‐moderate systemic lupus erythematosus: A multicenter randomized, double‐blind, placebo‐controlled trial

“…DHEA has been reported to reduce the release of IL-6 from human mononuclear cells in vitro (3,10). Decreases in complement levels without SLE flare during DHEA treatment were observed in this study as well as in two other clinical studies (11,12). A presumed reduction in IL-6 production during DHEA administration might be associated with a reduction in the levels of C3, which is an acute-phase reactant (13).…”

“…Furthermore, in two subsequent multicenter studies, DHEA treatment at a dosage of 200 mg/day allowed for a reduction in the prednisone dosage to near-physiologic levels in a significantly greater proportion of patients than did placebo (11), and it stabilized or improved the SLE activity and its symptoms and prevented bone loss (12).…”

Effects of prasterone on disease activity and symptoms in women with active systemic lupus erythematosus

“…This requirement was based upon the outcome of an earlier Genelabs study, which revealed (23). The importance of requiring minimum disease activity as a criterion for enrollment into SLE clinical trials is consistent with the approach taken in other clinical trials of other rheumatologic conditions.…”

“…While the double-blind study was ongoing, the protocol was subsequently amended to incorporate a baseline SLEDAI score of Ͼ2 as an additional entry requirement. This requirement was based upon the outcome of an earlier Genelabs study, which revealed that SLE patients with little or no disease activity (SLEDAI Յ2) are likely to exhibit a high response regardless of treatment (23).…”

“…In open-label and placebo-controlled studies, Van Vollenhoven et al (21,22) reported that SLE patients receiving oral prasterone 200 mg/day had improvement in a number of outcome variables, including reduction of steroid dosages, the number of disease flares, and global assessments of disease activity (21,22). In an initial phase II/III trial comparing placebo with 100 and 200 mg/day of prasterone, it was demonstrated that 200 mg/day of prasterone allowed a sustained reduction in the glucocorticoid dosage (23). In addition, delay in time to SLE flare has been reported for women treated with prasterone (24).…”