Chronic pelvic pain and endometriosis
Joseph S. Sanfilippo, Eduardo Lara-Torre, Veronica Gomez-Lobo in Sanfilippo's Textbook of Pediatric and Adolescent GynecologySecond Edition, 2019
More recently, the safety and efficacy of oral GnRH antagonists have been evaluated for the treatment of endometriosis in the adult population. This drug acts by competitively inhibiting the GnRH receptors in the pituitary gland, resulting in a rapid decrease in circulating gonadotropins and estradiol. Recent randomized phase 2 and phase 3 trials have demonstrated the ability of GnRH antagonists to significantly reduce the symptoms related to moderate and severe endometriosis.78 However, these agents were also found to result in hypoestrogenic side effects, including reduced BMD, increased lipid levels, and vasomotor symptoms.78 The pharmaceutical name, Elagolix, is now approved in the United States and Canada under the trade name, Orlissa. Partial suppression can be achieved with a dose of 150 mg daily (for up to 24 months) and full suppression with a higher regimen of 200 mg twice daily (for up to 6 months). Addback therapy is recommended with use of the higher dosing to reduce the risk of bone loss. Elagolix should not be considered a contraceptive and estrogen-containing contraceptive options have been shown to reduce efficacy so consideration towards progestin-only options or barrier protection should be used if appropriate. Studies using this drug in the adolescent population are lacking.
Medical Options for Uterine Fibroids in the Context of Reproduction
Botros R.M.B. Rizk, Yakoub Khalaf, Mostafa A. Borahay in Fibroids and Reproduction, 2020
Currently, available treatment options are restricted, and approved market medications are often used for short-term treatment to control HMB. Progestogens and COCs usually provide a brief improvement in HMB. The LNG-IUS is valuable in decreasing bleeding, but it is used only in women with a normal uterine cavity. These medications reduce bleeding by targeting the endometrium and do not diminish fibroid volume. GnRH agonists are highly effective in suppressing bleeding and reducing fibroids and uterine mass. Leuprolide acetate is FDA approved for presurgery short-term treatment. No hormonal add-back therapies have been approved as GnRH agonists for long-term treatment of fibroids. However, some medications currently under investigation in the United States, such as PRMs and oral GnRH antagonists, offer a promise of new fertility-sparing medical therapies that could provide a long-term treatment option for women with fibroids. Alternative treatment using UPA has recently been approved in Europe and Canada for the long-term management of symptomatic fibroids. Vilaprisan has been evaluated only in women with symptomatic fibroids, and it has an advantage over other SPRMs, such as UPA. Vilaprisan exhibits more rapid action on bleeding related to fibroids but shows effects with lower doses than other SPRMs. Elagolix is an FDA-approved oral treatment for controlling endometriosis with symptoms from a moderate to severe degree. A recent phase IIb study of therapy with elagolix combined with low-dose add-back therapy exhibited high efficiency and improvements in HMB. This combination treatment shows a low rate of hypoestrogenic side effects such as vasomotor signs and changes in BMD. Continuous studies of the pathogenesis of uterine fibroids and a new pharmacological target, nonhormonal effect, and long-term medical regimen to eradicate this disease are needed.
Endometriosis
S Paige Hertweck, Maggie L Dwiggins in Clinical Protocols in Pediatric and Adolescent Gynecology, 2022
Available in oral or intramuscular formsElagolix 150 mg daily or 200 mg twice dailyIs not approved for use in women under age 18
Emerging treatment options for uterine fibroids
Published in Expert Opinion on Emerging Drugs, 2018
Jacques Donnez, Pablo Arriagada, Olivier Donnez, Marie-Madeleine Dolmans
Three orally formulated GnRH receptor antagonists are currently well advanced in their clinical development. Elagolix (elagolix sodium; NBI-56418; NBI-56418, AbbVie) could have a range of potential applications for conditions like endometriosis, uterine fibroids, and prostate hyperplasia, and is thought to be an anti-cancer agent. Because of the antagonistic effect on the GnRH receptor, use of add-back therapy is required to counteract the anti-estrogenic impact when administered continuously. Elagolix is now being tested in two phase III studies comparing 6 and 12 months of treatment with the drug against use of a placebo or estradiol/norethindrone acetate. These studies are due to be completed in 2022. The second compound in this class is relugolix (TAK-385, Takeda/Myovant), with one phase III trial for uterine fibroids under way in and two multinational phase III trials initiated by Myovant, one in women with heavy menstrual bleeding associated with uterine fibroids, and the second in women with endometriosis-associated pain (NCT03049735, NCT03103087). The third compound, OBE-2109 (ObsEva), will shortly enter phase III of its program, with two trials investigating treatment of uterine fibroids (NCT03049735) and endometriosis (NCT03103087), including add-back therapy for up to 48 weeks.
Elagolix in the treatment of heavy menstrual bleeding associated with uterine fibroids in premenopausal women
Published in Expert Review of Clinical Pharmacology, 2021
Mohamed Ali, Sara A.R., Ayman Al Hendy
Starting from Phase II trials, elagolix was investigated in patients with endometriosis and UFs. The first stage of one Phase II study lasted 12 weeks and compared 3 groups with one another: a placebo control group; a group of patients receiving 150 mg elagolix once daily; and a third group receiving 250 mg once daily. Endometriosis-associated pain had decreased in all three groups by the end of the 12 weeks, as assessed by the Numeric Rating Scale. After 12 weeks, the patients of the placebo group were reallocated to one of the groups receiving elagolix. In this second stage, there was a further reduction of dysmenorrhea in both groups. Similar results were achieved for dyspareunia. Statistical significance was seen between elagolix 150 mg and placebo during weeks 8–12, as well as between elagolix 250 mg and placebo during weeks 4–8. Furthermore, a decrease in the use of prescription analgesics was seen in the elagolix groups, while the biggest improvement in quality of life was noted specifically in the elagolix 150 mg group [38].
Successes and failures of uterine leiomyoma drug discovery
Published in Expert Opinion on Drug Discovery, 2018
Mohamed Ali, Zunir Tayyeb Chaudhry, Ayman Al-Hendy
Elagolix (NBI-56,418), a short acting second-generation non-peptide GnRH antagonist, is one of the newest addition to the family of GnRH antagonists with the added advantage of an oral dosing. It has been primarily researched in endometriosis as opposed to uterine leiomyomas [18]. Elagolix has shown promise as it successfully suppresses LH and FSH in a dose-dependent manner with a better side-effect profile than the other agents in this category [18]. A proof-of-concept study was conducted in 2017 regarding efficacy of Elagolix for UFs and heavy menstrual bleeding, and the study concluded that an oral 300 mg BID regimen of Elagolix showed a 36% mean reduction in leiomyoma and uterine volume when compared to a placebo that had a 7% mean increase [21]. Elagolix is currently in phase III trials for endometriosis but may show promise in uterine fibroid management in the future [22].
Related Knowledge Centers
- Benign Prostatic Hyperplasia
- Uterine Fibroid
- Menopause
- Pain
- Endometriosis
- Prostate Cancer
- Gonadotropin-Releasing Hormone Antagonist
- Heavy Menstrual Bleeding
- Oral Administration
- Side Effect