Elagolix Relieves Short-Term Menstrual Pain, Dysmenorrhea in Endometriosis
Although elagolix had hypoestrogenic effects, most were not significant, particularly in the lower-dose group.
Women with endometriosis experienced short-term relief of dysmenorrhea and menstrual pain when taking the gonadotropin-releasing hormone antagonist elagolix, according to results from 2 large randomized, placebo-controlled trials published in the New England Journal of Medicine.
Hugh S. Taylor, MD, from the Department of Obstetrics, Gynecology, and Reproductive Sciences at Yale School of Medicine in New Haven, Connecticut, and colleagues enrolled patients with endometriosis as confirmed via surgery in the Elaris Endometriosis I (EM-I; ClinicalTrials.gov identifier: NCT01620528; n=872) Elaris Endometriosis II (EM-II; ClinicalTrials.gov identifier: NCT01931670; n=817) trials, Patients had moderate to severe endometriosis-associated pain and received 150 mg elagolix once daily, 200 mg elagolix twice daily, or placebo for 6 months.
The researchers analyzed the women's responses to the medication regarding improvements in nonmenstrual pelvic pain and dysmenorrhea at 6-month follow-up.
There were significantly more patients in both elagolix groups who saw clinical improvement in dysmenorrhea and nonmenstrual pelvic pain compared with the placebo group. In the Elaris EM-1 trial, 46.4% of patients in the low-dose elagolix group and 75.8% of patients in the high-dose elagolix group experienced improvements in dysmenorrhea compared with 19.6% of patients in the placebo group (P <.001). In the Elaris EM-II trial, 43.4% of low-dose elagolix and 72.4% of high-dose elagolix patients reported clinical improvement for dysmenorrhea compared with 22.7% of patients in the placebo group (P <.001).
Regarding nonmenstrual pain, 50.4% of patients in the low-dose elagolix group and 54.5% of patients in the high-dose elagolix group in the Elaris EM-I trial reported improved nonmenstrual pelvic pain compared with 36.5% of patients taking placebo (P =.003). In the Elaris EM-II trial, 49.8% of patients in the low-dose group and 57.8% of patients in the high-dose group reported nonmenstrual pelvic pain clinical improvement compared with 36.5% of patients in the placebo group (P <.001). The researchers noted these results were sustained at 6 months as well.
"Oral elagolix had hypoestrogenic effects — including reduced bone mineral density, increased lipid levels, and an increased incidence of hot flushes — that were similar to those of injectable [gonadotropin-releasing hormone] agonists, but the magnitude of the effects may differ," the researchers wrote.
Both elagolix doses had an effect on bone mineral density, which was significant compared with placebo. However, the lower dose of elagolix and placebo had a less significant range of difference (−0.41% to −1.28%) compared with the higher dose of elagolix.
In addition, there were no adverse effects on the endometrium after 6 months of elagolix treatment.
"This finding suggests that elagolix was associated with an antiproliferative effect at each dose and with endometrial atrophy at the higher dose, which was consistent with decreases in endometrial thickness at this dose," the researchers concluded.
Disclosures: The researchers report financial support from AbbVie.
Taylor HS, Giudice LC, Lessey BA, et al. Treatment of endometriosis-associated pain with elagolix, an oral GnRH antagonist [published online May 19, 2017]. N Engl J Med. doi:10.1056/NEJMoa1700089