Journal of the Women’s Health: Published on April 2021

Endometriosis is an estrogen-dependent, inflammatory condition marked anatomically by the presence of extrauterine lesions containing endometrial glands and stroma. Affecting an estimated 6%–10% of women, endometriosis is one of the most common gynecologic conditions among reproductive-age women.

The symptoms of endometriosis have a tremendous impact on patients' lives, negatively influencing quality of life, emotional well-being, intimate relationships, work life, and daily activities. Endometriosis-associated pelvic pain, which often manifests as dysmenorrhea, nonmenstrual pelvic pain (NMPP), and dyspareunia, plays a dominant role in the effect of endometriosis on patients' daily lives and physical functioning.

A plethora of pharmaceutical agents are prescribed for management of pain associated with endometriosis, although few of these have been approved for this indication by regulatory bodies.

TAKE HOME MESSAGE:

Elagolix is the first orally administered FDA-approved treatment option for endometriosis-associated pain in more than 10 years.

As a newer treatment option, clinicians may be unfamiliar with elagolix and its application in clinical practice. The aim of this review is to provide a practical guide for use of elagolix based on available evidence and clinical experience.

Clinical evidence has shown that elagolix at both approved doses (150 mg once daily and 200 mg twice daily) is effective for reducing symptoms of pelvic pain (dysmenorrhea, nonmenstrual pelvic pain, and dyspareunia), improving quality of life, and decreasing use of rescue analgesics (nonsteroidal anti-inflammatory drugs and/or opioids).

Recommendations for patient selection

Elagolix Dosing

Dosing regimens for elagolix are: 150 mg once daily and 200 mg twice daily. Both doses were effective for improving dysmenorrhea and NMPP, with significantly greater proportions of women demonstrating a clinically meaningful reduction in each pain symptom in association with decreased or stable use of rescue analgesics compared with placebo at month 3

During long-term extension studies, which increased total treatment duration to 12 months, sustained or improved reductions in dysmenorrhea, NMPP, and dyspareunia were observed.

Treatment with elagolix should be initiated at the lowest effective dose. Although for most patients, the lowest effective starting dose will be 150 mg once daily, there are scenarios where beginning treatment with the higher dosing regimen is appropriate.

For example, initiating therapy with elagolix 200 mg twice daily is recommended for patients in whom dyspareunia is the main symptom and may be considered for patients with severe NMPP or a history of endometriosis pain severe enough to require opioid analgesics.

Elagolix dose determinations are not influenced by body weight/BMI or by presence of renal impairment, end-stage renal disease, or mild hepatic impairment.

Treatment should be limited to 6 months of elagolix 150 mg once daily for women with moderate hepatic impairment (Child-Pugh B), and is contraindicated in patients with severe hepatic impairment (Child-Pugh C).

A follow-up assessment of response to therapy and tolerability should be conducted within 3 months or less of starting elagolix.

Safety Considerations

Elagolix is well tolerated, with less pronounced hypoestrogenic effects compared with GnRH agonists.

As this was an anticipated effect, special attention was given to the occurrence of vasomotor symptoms and to changes in BMD, lipids, and endometrial thickness.

In the pivotal studies, hot flushes were reported by 24% of women who received elagolix 150 mg once daily and by up to 48% of women who received elagolix 200 mg twice daily.