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Long-Term Outcomes of Elagolix in Women With Endometriosis: Results From Two Extension Studies

Surrey, Eric, MD; Taylor, Hugh S., MD; Giudice, Linda, MD, PhD; Lessey, Bruce A., MD, PhD; Abrao, Mauricio S., MD; Archer, David F., MD; Diamond, Michael P., MD; Johnson, Neil P., MD; Watts, Nelson B., MD; Gallagher, J. Chris, MD; Simon, James A., MD; Carr, Bruce R., MD; Dmowski, W. Paul, MD, PhD; Leyland, Nicholas, MD; Singh, Sukhbir S., MD; Rechberger, Tomasz, MD; Agarwal, Sanjay K., MD; Duan, W. Rachel, MD, PhD; Schwefel, Brittany, PhD; Thomas, James W., MS; Peloso, Paul M., MD, MSc; Ng, Juki, PharmD, PhD; Soliman, Ahmed M., MS, PhD; Chwalisz, Kristof, MD, PhD

doi: 10.1097/AOG.0000000000002675
Contents: Endometriosis: Original Research

OBJECTIVE: To evaluate the efficacy and safety of elagolix, an oral, nonpeptide gonadotropin-releasing hormone antagonist, over 12 months in women with endometriosis-associated pain.

METHODS: Elaris Endometriosis (EM)-III and -IV were extension studies that evaluated an additional 6 months of treatment after two 6-month, double-blind, placebo-controlled phase 3 trials (12 continuous treatment months) with two elagolix doses (150 mg once daily and 200 mg twice daily). Coprimary efficacy endpoints were the proportion of responders (clinically meaningful pain reduction and stable or decreased rescue analgesic use) based on average monthly dysmenorrhea and nonmenstrual pelvic pain scores. Safety assessments included adverse events, clinical laboratory tests, and endometrial and bone mineral density assessments. The power of Elaris EM-III and -IV was based on the comparison to placebo in Elaris EM-I and -II with an expected 25% dropout rate.

RESULTS: Between December 28, 2012, and October 31, 2014 (Elaris EM-III), and between May 27, 2014, and January 6, 2016 (Elaris EM-IV), 569 participants were enrolled. After 12 months of treatment, Elaris EM-III responder rates for dysmenorrhea were 52.1% at 150 mg once daily (Elaris EM-IV=50.8%) and 78.1% at 200 mg twice daily (Elaris EM-IV=75.9%). Elaris EM-III nonmenstrual pelvic pain responder rates were 67.8% at 150 mg once daily (Elaris EM-IV=66.4%) and 69.1% at 200 mg twice daily (Elaris EM-IV=67.2%). After 12 months of treatment, Elaris EM-III dyspareunia responder rates were 45.2% at 150 mg once daily (Elaris EM-IV=45.9%) and 60.0% at 200 mg twice daily (Elaris EM-IV=58.1%). Hot flush was the most common adverse event. Decreases from baseline in bone mineral density and increases from baseline in lipids were observed after 12 months of treatment. There were no adverse endometrial findings.

CONCLUSION: Long-term elagolix treatment provided sustained reductions in dysmenorrhea, nonmenstrual pelvic pain, and dyspareunia. The safety was consistent with reduced estrogen levels and no new safety concerns were associated with long-term elagolix use.

CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT01760954 and NCT02143713.

In women with endometriosis-associated pain, long-term elagolix treatment reduced dysmenorrhea, nonmenstrual pelvic pain, and dyspareunia, with a safety profile consistent with its mechanism of action.

Colorado Center for Reproductive Medicine, Lone Tree, Colorado; Yale School of Medicine, New Haven, Connecticut; the University of California, San Francisco, San Francisco, California; Greenville Health System, Greenville, South Carolina; the University of Sao Paulo and Hospital BP–A Beneficência Portuguesa de Sao Paulo, Sao Paulo, Brazil; Eastern Virginia Medical School, Norfolk, Virginia; Augusta University, Augusta, Georgia; Robinson Research Institute, University of Adelaide, Adelaide, Australia; Repromed Auckland, Auckland, New Zealand; Mercy Health Osteoporosis and Bone Health Services, Cincinnati, Ohio; Creighton University School of Medicine, Omaha, Nebraska; George Washington University, Washington, DC; the University of Texas Southwestern Medical Center, Dallas, Texas; the Institute for the Study and Treatment of Endometriosis, Oak Brook, Illinois; McMaster University, Hamilton, Ontario, Canada; the Department of Obstetrics, Gynecology & Newborn Care, University of Ottawa, Ottawa, Ontario, Canada; the Department of Gynecology, Lublin Medical University, Lublin, Poland; the Center for Endometriosis Research and Treatment, UC San Diego, La Jolla, California; and AbbVie Inc, North Chicago, Illinois.

Corresponding author: Eric Surrey, MD, Colorado Center for Reproductive Medicine, 10290 Ridgegate Circle, Lone Tree, CO 80124; email: ESurrey@colocrm.com.

AbbVie Inc. funded these studies and participated in the study design, research, analysis, data collection, interpretation of data, reviewing, and approval of the publication. Amy M. Spiegel, PhD, and Jane Rodgers, PhD, both of AbbVie Inc, provided medical writing assistance.

Financial Disclosure Dr. Surrey served on medical advisory boards; speaker for AbbVie and Ferring Laboratories. Dr. Taylor received research support from OvaScience and Pfizer; and was a consultant for AbbVie, Pfizer, Bayer, Obseva, and OvaScience. Dr. Giudice received research support from Bayer Healthcare; serves on advisory boards for AbbVie, NextGen Jane, and Myovant Pharmaceuticals; and was past-President of the World Endometriosis Society. Dr. Lessey was a study investigator; and received research support from AbbVie and Pfizer. Dr. Abrao was an advisor for AbbVie and BayerSchering; was a consultant for Olympus; was Editor-in-Chief of the Journal of Endometriosis and Pelvic Pain Disorders; and was a scientific advisor for CiceroDx. Dr. Archer received research support from AbbVie, TherapeuticsMD, Bayer HealthCare, Endoceutics, Glenmark, Shionogi, Symbio, and Radius; and received compensation from AbbVie, TherapeuticsMD, Bayer HealthCare, Endoceutics, Agile Pharmaceuticals, Exeltis/CHEMO France, and TEVA/HR Pharma for consulting. Dr. Diamond was a study investigator for AbbVie, ObsEva, and Bayer; received research support from AbbVie; and was a Board of Directors member and stockholder for Advanced Reproductive Care, Inc. Dr. Johnson was a study investigator; received research support from AbbVie; and received compensation for consultancy or speaker honoraria from Vifor Pharma and Guerbet, Bayer Pharma, Merck-Serono, and MSD. Dr. Watts received research support from Shire; received compensation from Amgen, Merck, Shire AbbVie, Amgen, Janssen, Merck, Radius, and Sanofi for consulting or speaker honoraria; and has stock options/royalties as an owner of OsteoDynamics. Dr. Gallagher was a consultant for AbbVie. Dr. Simon received research support from AbbVie, Actavis, Agile Therapeutics, Bayer Healthcare, New England Research Institute, Novo Nordisk, Palatin Technologies, Symbio Research, and TherapeuticsMD; was a speaker for Amgen, Eisai, Merck, Noven Pharmaceuticals, Novo Nordisk, and Shionogi; was a consultant for AbbVie, AMAG Pharmaceuticals, Amgen, Apotex, Ascend Therapeutics, JDS Therapeutics, Merck & Co, Noven Pharmaceuticals, Novo Nordisk, Nuelle, Perrigo Company, Radius Health, Regeneron Pharmaceutical, Sanofi SA, Sermonix Pharmaceuticals, Shionogi, Sprout Pharmaceuticals, Symbiotec Pharmalab, and TherapeuticsMD; and was a stockholder in Sermonix Pharmaceuticals. Dr. Carr was a study investigator; received research support from AbbVie and Agile Therapeutics; and served on the Repros Therapeutics Data and Safety Monitoring Board. Dr. Leyland received research support from AbbVie, Bayer, and Allergan; was a consultant for AbbVie, Bayer, Allergan, and Johnson & Johnson. Dr. Singh was a study investigator for Allergan, AbbVie, and Bayer; and was a speaker and advisor for Allergan, AbbVie, Bayer, Hologic, and Cooper Surgical. Dr. Rechberger was a study investigator; received research support from Astellas, Allergan, and Bayer; was a consultant for Astellas and Allergan; and received travel grants from Astellas and Allergan. Dr. Agarwal was a study investigator; received research support from AbbVie; and was a speaker for AbbVie. Drs. Duan and Schwefel, Mr. Thomas, and Drs. Peloso, Ng, Soliman, and Chwalisz are AbbVie employees who hold stock or stock options. Dr. Dmowski did not report any potential conflicts of interest.

Presented at the 73rd Annual Meeting of the American Society for Reproductive Medicine, October 28–November 1, 2017, San Antonio, Texas; and at the American College of Obstetricians and Gynecologists Annual Clinical and Scientific Meeting, April 27–30, 2018, Austin, Texas.

Each author has indicated that he or she has met the journal's requirements for authorship.

Received January 11, 2018. Received in revised form March 8, 2018. Accepted March 23, 2018.

© 2018 by The American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.