Grand Rounds

Elaris EM-III and Elaris EM-IV Results: Long-Term Endometriosis Outcomes Following Administration of Elagolix

BACKGROUND AND PURPOSE:

Elagolix is an oral, gonadotropin-releasing hormone (GnRH) antagonist
Previous studies demonstrated that elagolix reduced endometriosis pain with an acceptable safety profile (See ‘Related ObG Topics’ below)
- However, these studies provided data up to only 6 months of follow-up
Surrey et al. (Obstetrics and Gynecology, 2018) extended the above studies to evaluate the longer term efficacy and safety of elagolix

Extension studies of double-blind, placebo-controlled phase 3 trials of elagolix
Participants
- Premenopausal women, between 18 and 49 years old with a surgical diagnosis of endometriosis within the past 10 years
- Moderate or severe endometriosis pain
In these Elaris EM-III and Elaris IM-IV extension studies, there was a 6 month extended treatment phase and a 1 year follow up phase
- Patients were maintained on the same elagolix dose as previously taken, either elagolix 150 mg daily or elagolix 200 mg twice daily
Participants also took 400 international units vitamin D with 500–1,000 mg calcium throughout the study
Rescue medications as needed
- NSAIDs
- Opioid ‘according to country’
Primary efficacy endpoints
- Proportion of responders: Those with clinically meaningful pain reduction and
- Stable or decreased rescue analgesic use
Secondary assessments include impact on
- Dyspareunia | Dysmenorrhea | Pelvic pain | Use of rescue analgesic medications
Safety assessments were included in these studies, including adverse events that occurred after treatment was begun

After 12 months of treatment

Dysmenorrhea responder rate was
- 150 mg once daily: 52.1% (Elaris EM-III) and 50.8% (Elaris EM-IV)
- 200 mg twice daily: 78.1% (Elaris EM-III) and 75.9% (Elaris EM-IV)
Nonmenstrual pain responder rate was
- 150 mg once daily: 67.8% (Elaris EM-III) and 66.4% (Elaris EM-IV)
Dysmenorrhea responder rate was
- 150 mg once daily: 45.2% (Elaris EM-III) and 45.9% (Elaris EM-IV)
- 200 mg twice daily: 60.0% (Elaris EM-III) and 58.1% (Elaris EM-IV)
Hot flashes were the most common side effect, while severe adverse events occurred in less than 5% of women in Elaris EM-III and 8% of women in Elaris EM-IV
Additionally, decreases from baseline in bone mineral density and increases from baseline in lipids were observed after 12 months of treatment
- Lipid changes were overall small
  - “Favorable” changes: Increased HDL
  - “Unfavorable” changes: Increased LDL and TG
- Only 1 woman between the two studies had BMD Z-score below -2.0 (lower bound of normal)
Majority of participants reported improved endometriosis associated pain and quality of life improvements were also noted
When looking specifically at decreased opioid use for pain management, there was a 30% mean reduction with 150 mg and > 65% mean reduction in those participants taking 200 mg twice daily

Long-term elagolix treatment reduced dysmenorrhea, nonmenstrual pelvic pain, and dyspareunia
Adverse effects at 12 months similar to those at 6 months, including hot flashes
The authors conclude that these findings are consistent with mechanism of drug action, with lowering of estrogen levels
In select patients, efficacy of elagolix appears sustained at 1 year

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