Reductions in endometriosis-associated pain among women treated with elagolix are consistent across a range of baseline characteristics reflective of real-world patients

Abstract

Background: Elagolix is an oral, gonadotropin-releasing hormone (GnRH) receptor antagonist, that significantly reduces dysmenorrhea and non-menstrual pelvic pain (NMPP) in women with moderate to severe endometriosis-associated pain.

Methods: Data were pooled from two 6-month, placebo-controlled, phase 3 studies (Elaris Endometriosis [EM]-I and II) in which 2 doses of elagolix were evaluated (150 mg once daily and 200 mg twice daily). Pooled data from > 1600 women, aged 18-49, were used to evaluate the efficacy of elagolix and health-related quality of life (HRQoL) in prespecified subgroups of women with various baseline characteristics.

Results: Of the 1686 women treated, 1285 (76.2%) completed the studies. The percentages of women with clinically meaningful reductions in dysmenorrhea and NMPP were generally consistent by subgroup. Significant treatment by subgroup interaction was demonstrated for dysmenorrhea response in baseline analgesic use (p < 0.01) and previous history of pregnancy (p < 0.05) subgroups, and for NMPP response in the baseline NMPP score (p < 0.05) and history of pregnancy (p < 0.05) subgroups. Patient-reported reduction in pain at month 3 was significant across all subgroups taking elagolix 200 mg BID, and significant across most subgroups with elagolix 150 mg QD. Women across subgroups experienced improvement within each domain of the Endometriosis Health Profile-30 (EHP-30), although significant treatment by subgroup interactions were observed in several categories.

Conclusions: Elagolix was effective in reducing dysmenorrhea and NMPP, and improving HRQoL, compared with placebo across numerous subgroups of women with various baseline characteristics, covering a broad segment of the endometriosis disease and patient types.

Clinical trial registration: ClinicalTrials.gov: https://www.clinicaltrials.gov/ct2/show/NCT01620528 ; https://www.clinicaltrials.gov/ct2/show/NCT01931670 .

Keywords: Dysmenorrhea; Dyspareunia; Endometriosis; Gonadotropin-releasing hormone; Health-related quality of life.

Fig. 1

Co-primary endpoints at month 3 for integrated Elaris EM-I and Elaris EM-II by baseline demographic subgroups. A Dysmenorrhea responders. B Non-menstrual pelvic pain responders. Ratios equal the number of responders over the total number of women in each treatment group per subgroup. Green indicates placebo, purple indicates elagolix 150 mg QD and orange indicates elagolix 200 mg BID. BID twice daily; BMI body mass index; QD once daily

Fig. 2

Co-primary endpoints at month 3 for integrated Elaris EM-I and Elaris EM-II by baseline disease severity subgroups. The treatment by subgroup interaction was significant (*p < 0.05, **p < 0.01). p values were obtained from a logistic regression model: responder/non-responder = base pain score + treatment + subgroup + treatment × subgroup for dysmenorrhea responders by previous analgesic use and history of pregnancy at baseline subgroups (A), and non-menstrual pelvic pain responders, non-menstrual pelvic pain baseline score, and history of pregnancy at baseline subgroups (B). Previous GnRH therapy includes both GnRH agonists and antagonists. Ratios equal the number of responders over the total number of women in each treatment group per subgroup. Green indicates placebo, purple indicates elagolix 150 mg QD, and orange indicates elagolix 200 mg BID. BID twice daily; DYS dysmenorrhea; DYSP dyspareunia; GnRH gonadotropin-releasing hormone; NARC narcotic/opioid; NMPP non-menstrual pelvic pain; NSAID non-steroidal anti-inflammatory drug; QD once daily

Fig. 3

Patient Global Impression of Change (PGIC) at month 3 for integrated Elaris EM-I and Elaris EM-II by baseline demographic subgroups. PGIC uses a 7-point scale ranging from 1 = very much improved through 7 = very much worse. p values were obtained from a logistic regression model: “very much” or “much improved/otherwise” = treatment + subgroup + treatment × subgroup. p values for between-group comparisons were obtained using a contrast within the subgroup from the logistic regression model. *p < 0.05. Green indicates placebo, purple indicates elagolix 150 mg QD, and orange indicates elagolix 200 mg BID. BID twice daily; BMI body mass index; QD once daily

Fig. 4

Patient Global Impression of Change (PGIC) at month 3 for integrated Elaris EM-I and Elaris EM-II by baseline disease severity subgroups. PGIC uses a 7-point scale ranging from 1 = very much improved through 7 = very much worse. p values were obtained from a logistic regression model: “very much” or “much improved/otherwise” = treatment + subgroup + treatment × subgroup. p values for between-group comparisons were obtained using a contrast within the subgroup from the logistic regression model. *p < 0.05. Green indicates placebo, purple indicates elagolix 150 mg QD, and orange indicates elagolix 200 mg BID. BID twice daily; DYS dysmenorrhea; DYSP dyspareunia; GnRH gonadotropin-releasing hormone; NARC narcotic/opioid; NMPP non-menstrual pelvic pain; NSAID non-steroidal anti-inflammatory drug; QD once daily