Elagolix Treatment for Up to 12 Months in Women With Heavy Menstrual Bleeding and Uterine Leiomyomas.

Abstract

OBJECTIVE:

To investigate the safety and efficacy of elagolix, an oral gonadotropin-releasing hormone antagonist, with hormonal add-back therapy for up to 12 months in women with heavy menstrual bleeding associated with uterine leiomyomas.

METHODS:

Elaris UF-EXTEND was a phase 3 extension study that evaluated an additional 6 months (up to 12 months total) of elagolix 300 mg twice daily with hormonal add-back therapy (estradiol 1 mg and norethindrone acetate 0.5 mg once daily) in women who completed an initial 6 months of the same treatment in one of two preceding phase 3 studies. The primary endpoint was the percentage of women with both less than 80 mL menstrual blood loss during final month and a 50% or greater reduction in menstrual blood loss from baseline to final month. Safety evaluations included adverse events and bone mineral density changes. The planned sample size of UF-EXTEND was based on estimated rollover and discontinuation rates in the two preceding studies.

RESULTS:

From September 2016 to March 2019, 433 women were enrolled in UF-EXTEND. Of these women, 218 received up to 12 months of elagolix with add-back therapy; the mean±SD age of this group was 42.4±5.4 years and 67.3% were black. The percentage of women who met the primary endpoint in this elagolix with add-back group was 87.9% (95% CI [83.4-92.3]). The most frequently reported adverse events with up to 12 months of elagolix plus add-back therapy were hot flush (6.9%), night sweats (3.2%), headache (5.5%), and nausea (4.1%). Mean percent decreases in bone mineral density from baseline to extension month 6 were significantly less with elagolix plus add-back therapy than with elagolix alone {between-group difference in lumbar spine: -3.3 (95% CI [-4.1 to -2.5])}.

CONCLUSION:

Up to 12 months of elagolix with add-back therapy provided sustained reduction in menstrual blood loss in women with uterine leiomyomas, with the addition of add-back therapy attenuating the hypoestrogenic effects of elagolix alone. No new or unexpected safety concerns were associated with an additional 6 months of elagolix with addback therapy.

CLINICAL TRIAL REGISTRATION:

ClinicalTrials.gov, NCT02925494.

FUNDING SOURCE:

AbbVie Inc funded this study.

• Authors: James A Simon, Ayman Al-Hendy, David F Archer, Kurt T Barnhart, Linda D Bradley, Bruce R Carr, Thomas Dayspring, Eve C Feinberg, Veronica Gillispie, Sandra Hurtado, JinHee Kim, Ran Liu, Charlotte D Owens, Ozgul Muneyyirci-Delale, Alice Wang, Nelson B Watts, William D Schlaff
• Journal: Obstetrics and gynecology (Obstet Gynecol) Vol. 135 Issue 6 Pg. 1313-1326 (06 2020) ISSN: 1873-233X [Electronic] United States
• PMID: 32459423 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Hydrocarbons, Fluorinated
• Pyrimidines
• Gonadotropin-Releasing Hormone
• Estradiol
• elagolix
• Norethindrone

Topics

• Adult
• Bone Density (drug effects)
• Double-Blind Method
• Drug Therapy, Combination
• Estradiol (administration & dosage, adverse effects)
• Female
• Gonadotropin-Releasing Hormone (antagonists & inhibitors)
• Headache (etiology)
• Hot Flashes (etiology)
• Humans
• Hydrocarbons, Fluorinated (administration & dosage, adverse effects)
• Leiomyoma (complications, drug therapy, pathology)
• Menorrhagia (blood, drug therapy, etiology)
• Middle Aged
• Nausea (etiology)
• Norethindrone (administration & dosage, adverse effects)
• Pyrimidines (administration & dosage, adverse effects)
• Quality of Life
• Uterine Neoplasms (complications, drug therapy, pathology)