Treatment of Endometriosis-Associated Pain with Elagolix, an Oral GnRH Antagonist: Results from a Phase 2, Randomized Controlled Study
Abstract
Purpose
Elagolix is a novel, oral GnRH antagonist that dose-dependently suppresses estradiol levels. This study evaluated safety and efficacy of elagolix vs. leuprorelin acetate (LA) and placebo in women with endometriosis-associated pain.
Methods
In this multicenter, double-blind study, women with laparoscopically confirmed endometriosis were randomized to oral elagolix 150 or 250 mg once daily, placebo or 3.75 mg LA intramuscularly (i.m.) monthly for 12 weeks. Placebo and LA patients were re-randomized to elagolix, and elagolix patients continued treatment for another 12 weeks.
Results
Baseline demographics were similar among groups (mean age 31.7 years). Significantly greater reductions in monthly mean pelvic pain compared with placebo (p<0.05) were observed in both elagolix doses at week 4, elagolix 250 mg at week 8 and LA at weeks 4, 8 and 12. The mean (95% CI) percentage change in spinal bone mineral density (BMD) from baseline at week 12 was -1.05 (-1.68, -0.43), -0.80 (-1.53, -0.07) and -1.63 (-2.28, -0.99) for elagolix 150-mg, 250-mg and LA groups, respectively, compared with a mean percentage increase in placebo group (0.11 [-0.50, 0.71]). Headache was the most common adverse event for all treatment groups.
Conclusions
Both elagolix and LA reduced endometriosis-associated pain for up to 24 weeks of treatment and were associated with generally acceptable safety profiles in this study. Based on relatively small changes from baseline to week 12 in BMD, elagolix may offer a potential long-term treatment option for endometriosis-associated pain in affected women. Larger clinical studies with elagolix are warranted.
Trial Registration
Clinicaltrials.gov Identifier: NCT00797225.
Get full access to this article
View all access and purchase options for this article.
References
1. Giudice L.C. Clinical practice: endometriosis. N Engl J Med. 2010; 362(25): 2389–2398.
2. Ferrero S., Remorgida V., Venturini P.L. Current pharmacotherapy for endometriosis. Expert Opin Pharmacother. 2010; 11(7): 1123–1134.
3. Practice Committee of American Society for Reproductive Medicine. Treatment of pelvic pain associated with endometriosis. Fertil Steril. 2008; 90(5)(Suppl): S260–S269.
4. Kennedy S, Bergqvist A, Chapron C, et al.; ESHRE Special Interest Group for Endometriosis and Endometrium Guideline Development Group. ESHRE guideline for the diagnosis and treatment of endometriosis. Hum Reprod. 2005; 20(10): 2698–2704.
5. Bulun S.E., Cheng Y.H., Pavone M.E.et al. Estrogen receptor-beta, estrogen receptor-alpha, and progesterone resistance in endometriosis. Semin Reprod Med. 2010; 28(1): 36–43.
6. Dunselman GA, Vermeulen N, Becker C, et al.; European Society of Human Reproduction and Embryology. ESHRE guideline: management of women with endometriosis. Hum Reprod. 2014; 29(3): 400–412.
7. Guo S.W. Recurrence of endometriosis and its control. Hum Reprod Update. 2009; 15(4): 441–461.
8. Tandoi I., Somigliana E., Riparini J., Ronzoni S., Vigano’ P., Candiani M. High rate of endometriosis recurrence in young women. J Pediatr Adolesc Gynecol. 2011; 24(6): 376–379.
9. Olive D.L. Gonadotropin-releasing hormone agonists for endometriosis. N Engl J Med. 2008; 359(11): 1136–1142.
10. Brown J., Pan A., Hart R.J. Gonadotrophin-releasing hormone analogues for pain associated with endometriosis. Cochrane Database Syst Rev. 2010; 12(12): CD008475.
11. Surrey E.S. Gonadotropin-releasing hormone agonist and add-back therapy: what do the data show? Curr Opin Obstet Gynecol. 2010; 22(4): 283–288.
12. Struthers R.S., Nicholls A.J., Grundy J.et al. Suppression of gonadotropins and estradiol in premenopausal women by oral administration of the nonpeptide gonadotropin-releasing hormone antagonist elagolix. J Clin Endocrinol Metab. 2009; 94(2): 545–551.
13. Carr B., Dmowski W.P., O'Brien C.et al. Elagolix, an oral GnRH antagonist, versus subcutaneous depot medroxyprogesterone acetate for the treatment of endometriosis: effects on bone mineral density. Reprod Sci. 2014; 21(11): 1341–1351.
14. Diamond M.P., Carr B., Dmowski W.P.et al. Elagolix treatment for endometriosis-associated pain: results from a phase 2, randomized, double-blind, placebo-controlled study. Reprod Sci. 2014; 21(3): 363–371.
15. Biberoglu K.O., Behrman S.J. Dosage aspects of danazol therapy in endometriosis: short-term and long-term effectiveness. Am J Obstet Gynecol. 1981; 139(6): 645–654.
16. Carr B., Giudice L., Dmowski W.et al. Elagolix, an oral GnRH antagonist for endometriosis-associated pain: a randomized controlled study. J Endometriosis. 2013; 5(3): 105–115.
17. Cauley JA, Ewing SK, Taylor BC, et al.; Osteoporotic Fractures in Men Study (MrOS) Research Group. Sex steroid hormones in older men: longitudinal associations with 4.5-year change in hip bone mineral density: the Osteoporotic Fractures in Men study. J Clin Endocrinol Metab. 2010; 95(9): 4314–4323.
18. Baim S., Wilson C.R., Lewiecki E.M., Luckey M.M., Downs R.W. Jr., Lentle B.C. Precision assessment and radiation safety for dual-energy X-ray absorptiometry: position paper of the International Society for Clinical Densitometry. J Clin Densitom. 2005; 8(4): 371–378.
19. Lupron Depot® (leuprolide acetate for depot suspension) 3.75 mg [package insert]. North Chicago, IL, USA: AbbVie Inc.; 2013.
20. Schlaff W.D., Carson S.A., Luciano A., Ross D., Bergqvist A. Subcutaneous injection of depot medroxyprogesterone acetate compared with leuprolide acetate in the treatment of endometriosis-associated pain. Fertil Steril. 2006; 85(2): 314–325.
21. Kelly T., Yang W., Chen C.S., Reynolds K., He J. Global burden of obesity in 2005 and projections to 2030. Int J Obes (Lond). 2008; 32(9): 1431–1437.
22. Macedo A., Baños J.E., Farré M. Placebo response in the prophylaxis of migraine: a meta-analysis. Eur J Pain. 2008; 12(1): 68–75.
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
Cite
Cite
Cite
OR
Download to reference manager
If you have citation software installed, you can download citation data to the citation manager of your choice
Information, rights and permissions
Information
Published In
Article first published online: May 23, 2015
Issue published: April-June 2015
Keywords
Authors
Metrics and citations
Metrics
Journals metrics
This article was published in Journal of Endometriosis and Pelvic Pain Disorders.
View All Journal MetricsPublication usage*
Total views and downloads: 771
*Publication usage tracking started in December 2016
Publications citing this one
Receive email alerts when this publication is cited
Web of Science: 26 view articles Opens in new tab
Crossref: 24
- Short-term Use of GnRH Antagonist for Severe Pain in Endometriosis
- Pharmacokinetic considerations for gonadotropin-releasing hormone agonists and antagonists to treat endometriosis
- Current and emerging therapies for endometriosis-associated pain: a review
- Comparative Analysis of Medical Interventions to Alleviate Endometriosis-Related Pain: A Systematic Review and Network Meta-Analysis
- A systematic literature review on patient-reported outcome domains and measures in nonsurgical efficacy trials related to chronic pain associated with endometriosis: an urgent call to action
- Investigational drugs for the treatment of dysmenorrhea
- A review of phase II and III drugs for the treatment and management of endometriosis
- A systematic review to determine use of the Endometriosis Health Profiles to measure quality of life outcomes in women with endometriosis
- Efficacy and safety of oral gonadotropin-releasing hormone antagonists in moderate-to-severe endometriosis-associated pain: a systematic review and network meta-analysis
- Medical and surgical interventions to improve the quality of life for endometriosis patients: a systematic review
- View More
Figures and tables
Figures & Media
Tables
View Options
Access options
If you have access to journal content via a personal subscription, university, library, employer or society, select from the options below:
I am signed in as:
View my profileSign out
I can access personal subscriptions, purchases, paired institutional access and free tools such as favourite journals, email alerts and saved searches.
loading institutional access options
Alternatively, view purchase options below:
Purchase 24 hour online access to view and download content.
Access journal content via a DeepDyve subscription or find out more about this option.
