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PMID-31971678 – Elagolix for Uterine Fibroids Phase III

PMID-31971678 – Elagolix for Uterine Fibroids Phase III

Schlaff WD, Ackerman RT, Al-Hendy A, Archer DF, Barnhart KT, Bradley LD, Carr BR, Feinberg EC, Hurtado SM, Kim J, Liu R, Mabey RG Jr, Owens CD, Poindexter A, Puscheck EE, Rodriguez-Ginorio H, Simon JA, Soliman AM, Stewart EA, Watts NB, Muneyyirci-Delale O. Elagolix for Heavy Menstrual Bleeding in Women with Uterine Fibroids. N Engl J Med. 2020;382(4):328-340.

Quick Reference

Property Value
PMID 31971678
DOI 10.1056/NEJMoa1904351
Year 2020
Journal New England Journal of Medicine
Study Type RCT (Phase III, two replicate trials)
Evidence Level I
Sample Two trials with premenopausal women with heavy menstrual bleeding due to uterine fibroids
Peptide(s) Studied Elagolix

Key Findings

  • Elagolix 300 mg BID with hormonal add-back therapy (estradiol 1 mg / norethindrone acetate 0.5 mg) was effective in reducing heavy menstrual bleeding
  • Primary endpoint response rates: approximately 68-76% elagolix + add-back vs 9-10% placebo
  • Hormonal add-back therapy attenuated hypoestrogenic side effects, particularly bone density loss
  • Clinically meaningful reduction in menstrual blood loss sustained throughout the treatment period
  • The combination approach allowed higher elagolix dosing while mitigating estrogen-deprivation effects

Study Design

Two replicate, randomized, double-blind, placebo-controlled, Phase III trials (Elaris UF-I and UF-II). Premenopausal women with heavy menstrual bleeding associated with uterine fibroids were randomized to elagolix 300 mg BID plus add-back therapy, elagolix 300 mg BID alone, or placebo for 6 months. Primary endpoint was menstrual blood loss volume reduction below 80 mL per cycle and at least 50% reduction from baseline.

Limitations

  • Six-month treatment duration
  • Add-back therapy required to manage side effects
  • Twice-daily dosing may affect adherence
  • No comparison with surgical interventions (myomectomy, hysterectomy) or uterine artery embolization
  • No fertility outcomes assessed

Clinical Relevance

These trials supported the FDA approval of elagolix with add-back therapy (marketed as Oriahnn) in 2020 for management of heavy menstrual bleeding associated with uterine fibroids in premenopausal women. The add-back therapy strategy — using low-dose estrogen/progestin alongside the GnRH antagonist — was innovative in allowing effective uterine fibroid treatment while preserving bone health, addressing a key limitation of older GnRH agonist approaches.

Related

#research #RCT #peptide #reproductive #evidence-level-I