Elagolix 治疗子宫内膜异位症女性的长期结局：两项扩展研究结果。
Long-Term Outcomes of Elagolix in Women With Endometriosis: Results From Two Extension Studies.
机构信息
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.
出版信息
Obstet Gynecol. 2018 Jul;132(1):147-160. doi: 10.1097/AOG.0000000000002675.
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 550.8%) and 78.2% at 200 mg twice daily (Elaris EMIV 575.9%). Elaris EM-III nonmenstrual pelvic pain responder rates were 67.5% at 150 mg once daily (Elaris EM-IV 566.4%) and 69.1% at 200 mg twice daily (Elaris EM-IV 567.2%).”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.
目的
评估口服非肽类促性腺激素释放激素拮抗剂依戈洛昔在子宫内膜异位症相关疼痛女性中 12 个月的疗效和安全性。
方法
Elaris 子宫内膜异位症（EM）-III 和 -IV 是两项扩展研究，在两项为期 6 个月的双盲、安慰剂对照的 3 期试验（共 12 个连续治疗月，使用两种依戈洛昔剂量[每日一次 150mg 和每日两次 200mg]）结束后，评估了另外 6 个月的治疗。主要疗效终点是根据平均每月痛经和非经期盆腔疼痛评分，基于临床有意义的疼痛减轻和稳定或减少急救止痛药物使用的应答者比例。安全性评估包括不良事件、临床实验室检查、子宫内膜和骨密度评估。Elaris EM-III 和 -IV 的效能基于 Elaris EM-I 和 -II 与安慰剂的比较，预计有 25%的脱落率。
结果
2012 年 12 月 28 日至 2014 年 10 月 31 日（Elaris EM-III）和 2014 年 5 月 27 日至 2016 年 1 月 6 日（Elaris EM-IV）期间，共纳入 569 名参与者。治疗 12 个月后，Elaris EM-III 组痛经的应答率为每日 150mg 一次组 52.1%（Elaris EM-IV 为 550.8%），每日 200mg 两次组 78.2%（Elaris EM-IV 为 575.9%）。Elaris EM-III 非经期盆腔疼痛的应答率为每日 150mg 一次组 67.5%（Elaris EM-IV 为 566.4%），每日 200mg 两次组 69.1%（Elaris EM-IV 为 567.2%）。治疗 12 个月后，Elaris EM-III 性交痛的应答率为每日 150mg 一次组 45.2%（Elaris EM-IV 为 45.9%），每日 200mg 两次组 60.0%（Elaris EM-IV 为 58.1%）。热潮红是最常见的不良事件。治疗 12 个月后，骨密度从基线下降，血脂从基线升高。未发现子宫内膜不良发现。
结论
长期依戈洛昔治疗可持续降低痛经、非经期盆腔疼痛和性交痛。安全性与雌激素水平降低一致，长期使用依戈洛昔没有新的安全性问题。
临床试验注册
ClinicalTrials.gov，NCT01760954 和 NCT02143713。
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