Safety and efficacy of elagolix (with and without add-back therapy) for the treatment of heavy menstrual bleeding associated with uterine leiomyomas: a systematic review and meta-analysis
Open Access
- 5 July 2021
- journal article
- review article
- Published by Springer Science and Business Media LLC in Middle East Fertility Society Journal
- Vol. 26 (1), 1-12
- https://doi.org/10.1186/s43043-021-00064-5
Abstract
Background: Heavy menstrual bleeding (HMB) is a common clinical finding in patients with uterine leiomyomas that can negatively impact their quality of life. Recently, a novel oral GnRH-antagonist (elagolix) has emerged as a possible therapeutic agent for this ailment. Herein data was pooled from clinical trials assessing the safety and efficacy of elagolix with and without add-back therapy. Main text: PubMed and Cochrane library were systematically searched for RCTs that measured the efficacy and safety of elagolix for the treatment of uterine fibroid-associated HMB. All safety and efficacy endpoints were compared between elagolix-alone, elagolix w/add-back therapy, and placebo. The primary efficacy endpoint was defined as the number of women who achieved menstrual blood loss (MBL) < 80 ml and a reduction in MBL from baseline of > 50% at the end of treatment. Secondary outcomes assessed included change in hemoglobin levels, incidence suppression of bleeding and amenorrhea, and the incidence of adverse events. The random effects model was used to pool data, and heterogeneity was assessed using I2. Our search identified 4 clinical trials meeting our PICO criteria, with a total of 916 patients. Analysis of the primary outcome revealed that elagolix-alone was the most effective treatment compared to both placebo (LOR = 3.47, CI = 3.03–3.91, p = 0.000, I2 = 0.0%) and add-back therapy (LOR = 0.64, CI = 0.12–1.16, p = 0.016, I2 = 43.1%). Furthermore, both elagolix groups (irrespective of add-back therapy) observed a significant improvement in post-treatment hemoglobin levels as compared to the placebo group (elagolix-alone vs PBO: LOR = 1.44, CI = 0.66–2.22, I2 = 66.0%, p = 0.000; elagolix-w/add-back therapy vs PBO: LOR = 1.22, CI = 0.78–1.66, I2 = 0.0%, p = 0.000). Concerning safety, while elagolix without add-back therapy had the highest overall incidence of adverse effects (elagolix-alone vs placebo LOR = 0.84, CI = 0.48–1.20, I2 = 7.8%, p = 0.000; elagolix-alone vs elagolix-w/add-back LOR = 0.68, CI = 0.09–1.26, p = 0.024, I2 = 64.6%), the incidence of serious (life threatening) adverse events between all 3 treatment groups was not statistically different. The inclusion of add-back therapy with elagolix made the treatment noticeably safer (elagolix-w/add-back vs placebo: LOR = 0.19, CI = − 0.10 to 0.48, I2 = 0.0%, p = 0.194) without seriously compromising its efficacy. Conclusion: High-quality evidence from 4 trials suggests that elagolix is an effective treatment for leiomyoma-associated HMB, with a marked improvement in all efficacy endpoints. Furthermore, the inclusion of add-back therapy in the treatment regimen should be considered as it mitigates the hypoestrogenic effects of elagolix.Keywords
This publication has 21 references indexed in Scilit:
- Elagolix, a Novel, Orally Bioavailable GnRH Antagonist under Investigation for the Treatment of Endometriosis-Related PainWomen's Health, 2015
- Menopausal hot flashes: Mechanisms, endocrinology, treatmentThe Journal of Steroid Biochemistry and Molecular Biology, 2013
- The impact of uterine leiomyomas: a national survey of affected womenAmerican Journal of Obstetrics and Gynecology, 2013
- Iron deficiency and fatigue in adolescent females with heavy menstrual bleedingHaemophilia, 2012
- The Cochrane Collaboration's tool for assessing risk of bias in randomised trialsBMJ, 2011
- Suppression of Gonadotropins and Estradiol in Premenopausal Women by Oral Administration of the Nonpeptide Gonadotropin-Releasing Hormone Antagonist ElagolixJournal of Clinical Endocrinology & Metabolism, 2009
- GnRH analogs: Options for endometriosis-associated pain treatmentJournal of Minimally Invasive Gynecology, 2006
- Incidence of migraine relative to menstrual cycle phases of rising and falling estrogenNeurology, 2006
- Suppression of Serum Luteinizing Hormone in Postmenopausal Women by an Orally Administered Nonpeptide Antagonist of the Gonadotropin-Releasing Hormone Receptor (NBI-42902)Journal of Clinical Endocrinology & Metabolism, 2006