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PMID-28525302 – Elagolix for Endometriosis Pain Phase III

PMID-28525302 – Elagolix for Endometriosis Pain Phase III

Taylor HS, Giudice LC, Lessey BA, Abrao MS, Kotarski J, Archer DF, Diamond MP, Surrey E, Johnson NP, Watts NB, Gallagher JC, Simon JA, Carr BR, Dmowski WP, Leyland N, et al. Treatment of Endometriosis-Associated Pain with Elagolix, an Oral GnRH Antagonist. N Engl J Med. 2017;377(1):28-40.

Quick Reference

Property Value
PMID 28525302
DOI 10.1056/NEJMoa1700089
Year 2017
Journal New England Journal of Medicine
Study Type RCT (Phase III, two replicate trials)
Evidence Level I
Sample 872 (Elaris EM-I) and 817 (Elaris EM-II) women
Peptide(s) Studied Elagolix

Key Findings

  • Significantly greater proportion of women met clinical response criteria for dysmenorrhea with elagolix vs placebo at 3 months
  • Higher-dose elagolix (200 mg BID): 75.8% and 72.4% dysmenorrhea response rates across two trials (vs ~20% placebo)
  • Lower-dose elagolix (150 mg QD): also significantly superior to placebo for dysmenorrhea
  • Nonmenstrual pelvic pain significantly improved with both dosing regimens
  • Hypoestrogenic side effects occurred dose-dependently: hot flashes, elevated serum lipids, decreased bone mineral density
  • No adverse endometrial findings observed
  • First oral GnRH antagonist specifically developed and approved for endometriosis pain

Study Design

Two replicate, randomized, double-blind, placebo-controlled, Phase III trials (Elaris EM-I and EM-II). Women with surgically diagnosed endometriosis and moderate-to-severe pain were randomized to elagolix 150 mg once daily, elagolix 200 mg twice daily, or placebo for 6 months. Co-primary endpoints were the proportion of women with a clinically meaningful reduction in dysmenorrhea and nonmenstrual pelvic pain.

Limitations

  • Six-month treatment duration (long-term data limited)
  • Dose-dependent bone mineral density loss raises concern for extended use
  • Surgical confirmation of endometriosis required for enrollment (limits generalizability)
  • No active comparator (e.g., leuprolide or oral contraceptives)
  • No fertility outcomes assessed

Clinical Relevance

The Elaris EM-I/II trials were pivotal for FDA approval of elagolix (Orilissa) in 2018 as the first oral GnRH antagonist approved for endometriosis-associated pain. The availability of two dose levels allows clinicians to balance efficacy against hypoestrogenic side effects. This represented a major advance over injectable GnRH agonists by providing an oral, dose-titratable option with partial (rather than complete) estrogen suppression at the lower dose.

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