Sustained weight loss in patients treated with mifepristone for Cushing’s syndrome: a follow-up analysis of the SEISMIC study and long-term extension

BMC Endocrine Disorders

Dat Nguyen⁴  David Cram⁴  Harvey Kushner²  T. Brooks Vaughan¹  Henry G. Fein³ 

[1] Division of Endocrinology, Diabetes & Metabolism, University of Alabama at Birmingham School of Medicine, BDB 706, 1720 2nd Avenue South, Birmingham 35294, AL, USA;BioMedical Computer Research Institute, 9743 Redd Rambler Place, Philadelphia 19115, PA, USA;Johns Hopkins University School of Medicine and Sinai Hospital of Baltimore, 2435 W. Belvedere Avenue, Baltimore 21215, MD, USA;Corcept Therapeutics, 149 Commonwealth Drive, Menlo Park 94025, CA, USA

关键词: Weight loss;    SEISMIC;    Obesity;    Mifepristone;    Long-term;    Korlym;    Cushing’s syndrome;   

Others  :  1230191
DOI  :  10.1186/s12902-015-0059-5

 received in 2015-04-15, accepted in 2015-10-16,  发布年份 2015

【 摘 要 】

Background

Overweight and obesity are common among patients with Cushing’s syndrome (CS) and may persist in some patients even after ostensibly curative surgery, contributing to cardiometabolic dysfunction and increased cardiovascular risk. Mifepristone, a selective glucocorticoid receptor antagonist, was effective in controlling hyperglycemia in a 24-week trial of adults (N = 50) with endogenous CS and associated type 2 diabetes mellitus/impaired glucose tolerance or hypertension who had failed or were not candidates for surgery (SEISMIC, Study of the Efficacy and Safety of Mifepristone in the Treatment of Endogenous Cushing’s Syndrome). This analysis examines long-term weight change among patients who received mifepristone in SEISMIC and enrolled in a long-term safety extension (LTE) study.

Methods

Patients completing the 24-week SEISMIC study and subsequent 6-week off-drug safety evaluation were invited to enroll in the LTE study. Mifepristone doses at the end of SEISMIC were the LTE starting doses. Body weight measures were reviewed at baseline and week 24 of SEISMIC and at LTE month 6, 12, 18, 24, and final visit (last observation collected during the LTE study).

Results

Of the 30 patients enrolled in the LTE, evaluable weight data were available for 29 (20/29 female; mean age of 44.7 ± 11.2 years). These patients received mifepristone for a median of 29.2 months (range 8.4–41.9). Mean ± SD weight from SEISMIC baseline to LTE final visit decreased by 10.3 ± 16.3 kg (mean 105.4 ± 34.3 kg to 95.1 ± 32.9 kg), a 9.3 % decrease from baseline weight (P = 0.0008). Of the 29 LTE patients, 18 (62.1 %) lost ≥5 % of body weight by the end of the initial 24-week treatment period; this ≥5 % weight loss persisted in 83.3 % (15/18) at LTE final visit. Ten patients (34.5 %) lost ≥10 % of initial body weight by week 24 of SEISMIC, which persisted in 80 % at LTE final visit. No new safety signals were detected with long-term mifepristone use.

Conclusion

Clinically meaningful weight loss achieved during a 24-week study of mifepristone for CS persisted for two additional years in patients who remained on therapy. Long-term treatment with mifepristone appears to have a beneficial effect on weight in patients with endogenous CS.

Trial Registration

NCT00569582 (SEISMIC); NCT00936741 (Long-Term Extension).

【 授权许可】

   
2015 Fein et al.

【 图 表 】

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