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.
Checking for direct PDF access through Ovid
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.