Elagolix with add-back therapy found effective and tolerable for endometriosis pain

Elagolix with add-back therapy found effective and tolerable for endometriosis pain | Image Credit: © Chinnapong - © Chinnapong - stock.adobe.com.

Dysmenorrhea (DYS), nonmenstrual pelvic pain (NMPP), and fatigue are significantly improved by elagolix (ELA) with add-back (AB) therapy in patients with endometriosis, according to a recent study published in the American Journal of Obstetrics & Gynecology.¹

Approximately 10% of women worldwide are impacted by endometriosis, an inflammatory disease linked to pain and infertility. Patients with endometriosis often experience DYS, NMPP, dyspareunia (DYSP), and fatigue.

Moderate-to-severe endometriosis may be treated using ELA, an oral antagonist designed to be taken at either 150 mg once daily or 200 mg twice daily, described as low-dose therapy and high-dose therapy, respectively.

High-dose therapy has been linked to hypoestrogenic effects such as reduced bone mineral density (BMD), making the approved treatment duration limited to 6 months.² However, these hypoestrogenic effects may be mitigated through hormonal AB therapy.¹

Investigators conducted a study to evaluate the safety and efficacy of ELA 200 mg twice daily plus AB (ELA+AB) in endometriosis patients. The analysis was of an ongoing phase 3, 48-month trial evaluating the regimen’s efficacy, tolerability, and impact on BMD.

Participants included women aged 18 to 49 years reporting moderate-to-severe endometriosis-associated pain within 35 days before baseline. A surgical diagnosis of endometriosis within 10 years before screening was also necessary for inclusion.

These participants were randomized 4:1:2 to receive ELA+AB therapy, 6 months of ELA 200 mg twice daily monotherapy followed by 6 months of ELA+AB therapy, or placebo, respectively. In the monotherapy group, BMD changes were compared following ELA monotherapy vs ELA+AB therapy.

Individuals with chronic pelvic pain, systemic corticosteroid use before screening, depression history or post-traumatic stress disorder diagnosis, bone disease, clinically significant medical conditions, or conditions contraindicated for AB therapy use were excluded from the analysis.

Daily DYS and NMPP assessments at month 6 were recorded as the coprimary efficacy endpoints. These symptoms were measures using the 4-point Endometriosis Daily Pain Impact Diary. Secondary efficacy endpoints included changes in DYS and NMPP at months 12, 6 and 4, fatigue, DYSP and overall endometriosis-associated pain within the past 7 days.

Treatment-emergent adverse events were reported to determine tolerability. Additionally, BMD comparisons were conducted including lumbar spine, total hip, and femoral neck assessments.

There were 681 patients randomized, with 44% discontinuing the study drug. TEAEs were reported as the most common reason for discontinuation, followed by withdrawal of consent, lost to follow-up, and other. Participants were aged a mean 32.5 years, and similar DYS, NMPP, DYSP, overall pain, and fatigue scores were reported between groups at baseline.

The ELA+AB therapy group reported significantly improved DYS and NMPP at 6 months compared to the placebo group. Responder rates for DYS were 62.8% for ELA+AB therapy vs 23.7% for placebo. For NMPP, these rates were 51.3% vs 36.8%, respectively.

An increased clinical response was also reported for DYS at 12 months in the ELA+AB therapy group vs the placebo group, at 63.8% vs 29.1%. Similarly, NMPP response rates at 12 months were 54.3% vs 42.3%, respectively. Additional improvements found from ELA+AB therapy vs placebo included DYS and NMPP at months 12, 6, and 3, and fatigue at 6 months.

TEAEs were reported in 73.8% of patients receiving ELA+AB vs 66.8% of those receiving placebo. There were no significant differences in rates of severe TEAEs between groups, and rates of TAEs leading to discontinuation were 12.6% vs 9.8%, respectively. Hot flushes, nausea, and headache were the most common TEAEs in the ELA+AB group.

Alongside the placebo group, patients in the ELA+AB therapy group had a change in BMD from baseline to month 6 and month 12 under 1%. At month 6, a statistically significant difference in mean lumbar spine changes of -0.83% was reported in the ELA+AB therapy groups vs the placebo group, but differences in total hip and femoral neck were not statistically significant.

These results indicated significant improvements in endometriosis-associated pain up to 12 months with attenuated BMD loss from ELA+AB therapy vs ELA monotherapy at 6 months. Investigators concluded ELA+AB therapy is tolerated after 12 months of treatment.

References

1. Miller CE, Kim JH, Kroll R, et al. Efficacy, tolerability, and bone density outcomes of elagolix with add-back therapy for endometriosis-associated pain: twelve months of an ongoing randomized phase 3 trial. Am J Obstet Gynecol. 2024;231:630.e1-13. doi:10.1016/j.ajog.2024.06.040
2. Taylor HS, Giudice LC, Lessey BA, et al. Treatment of endometriosis-associated pain with elagolix, an oral GnRH antagonist. N Engl J Med. 2017;377(1):28-40. doi:10.1056/NEJMoa1700089