Endometriosis-Related Pain Reduction During Bleeding and Nonbleeding Days in Women Treated with Elagolix

Abstract

Objective: In this post hoc analysis, we evaluated the impact of elagolix on dysmenorrhea and nonmenstrual pelvic pain across menstrual period (bleeding days) and nonmenstrual (nonbleeding) days.

Methods: Data from two randomized, 6-month, placebo-controlled trials (Elaris Endometriosis (EM)-I and EM-II) of elagolix (150 mg once daily (QD) and 200 mg twice daily (BID)) in premenopausal women with moderate to severe endometriosis-associated pain (N = 1686) were pooled. Women recorded the presence of menstrual period and severity of dysmenorrhea or nonmenstrual pelvic pain in a daily electronic diary.

Results: At baseline, women in the placebo group and both elagolix treatment groups reported moderate or severe dysmenorrhea, on average, 81% of their menstrual period days and moderate/severe nonmenstrual pelvic pain, on average, 56% of their nonmenstrual (nonbleeding) days. Compared with placebo at month 6, elagolix-treated women had a significantly lower mean (standard deviation (SD)) percentage of menstrual period days with moderate or severe dysmenorrhea (elagolix 150 mg QD = 52.4 (38.9), p = 0.002; elagolix 200 mg BID = 38.5 (43.6), p < 0.001, placebo = 61.3 (33.7)) and a significantly lower mean (SD) percentage of nonmenstrual (nonbleeding) days with moderate or severe nonmenstrual pelvic pain (elagolix 150 mg QD = 31.1 (35.8), p < 0.001; elagolix 200 mg BID = 19.7 (29.9), p < 0.001; placebo = 35.6 (33.9)).

Conclusion: Following 6 months of elagolix treatment, women who still menstruated had a lower proportion of menstrual period days with moderate or severe dysmenorrhea compared with placebo, demonstrating pain reduction despite continued menses. Additionally, pain did not shift from dysmenorrhea to nonmenstrual pelvic pain, as the percentage of days with moderate or severe nonmenstrual pelvic pain was also reduced for elagolix-treated women compared with placebo.

Trial registration: The Elaris EM-I study is registered with the US National Library of Medicine, www.ClinicalTrials.gov, NCT01620528. The Elaris EM-II study is registered with the US National Library of Medicine, www.ClinicalTrials.gov, NCT01931670. Both studies are registered with the EU Clinical Trial Register, www.clinicaltrialsregister.ed, 2011-004295-11.

Keywords: bleeding; dysmenorrhea; elagolix; endometriosis; nonmenstrual pelvic pain.

Conflict of interest statement

S.K.A. was a study investigator, has received research support from AbbVie and Sobi, and has served on the speakers’ bureau for AbbVie. S.K.A. reports personal fees from AbbVie and Myovant. S.S.S. was a study investigator in therapeutic trials for endometriosis and fibroids sponsored by Allergan, AbbVie, and Bayer, and served as a speaker and advisor for Allergan, AbbVie, Bayer, Hologic, Myovant, and Cooper Surgical. D.F.A. was a study investigator and has received grant support from Actavis and Glenmark; research support from Myovant, Mithra, and ObsEva; grant support, honoraria, and travel support from Bayer Healthcare, Endoceutics, Merck, Radius Health, Shionogi, and TherapeuticsMD; honoraria and travel support from Exeltis/CHEMO France, Pfizer, Sermonix Pharmaceuticals, and TEVA/HR Pharma; research support and consulting fees from AbbVie; and honoraria and travel support from Agile Therapeutics and Innovagyn. He also has an equity interest in Agile Therapeutics and an equity interest in Innovagyn. Y.M. and K.G. are AbbVie employees and have stock or stock/options. K.C. was an employee of AbbVie Inc. at the time the study was conducted and owns stock. K.C. also reports patent for “Methods of treating heavy menstrual bleeding” (PCT/US2018/043321). E.S. was a study investigator, has received research support from AbbVie, and has served on medical advisory boards and speakers’ bureaus for AbbVie, Ferring, and DOT Labs. The authors report no other conflicts of interest in this work.

© 2021 Agarwal et al.

Figures

Figure 1

Mean number of bleeding and nonbleeding days at baseline, month 3, and month 6. Missing due to early discontinuation: month 3 (placebo, 0/726; 150 mg elagolix QD, 0/469; 200 mg BID elagolix, 1/469) and month 6 (placebo, 8/727; 150 mg elagolix QD, 2/468; 200 mg BID elagolix, 7/468). There were no statistically significant differences between either dose group and placebo for baseline age, body mass index, or mean dysmenorrhea or NMPP scores, except for the dysmenorrhea score in the elagolix 200 mg BID dose group (Elaris EM-II data, p = 0.03).

Figure 2

Mean number and mean percent of bleeding days with dysmenorrhea (A and B). Mean number and mean percent of nonbleeding days with nonmenstrual pelvic pain (C and D). p < 0.001 (***) and p < 0.01 (**) vs placebo for percent of women with “moderate or severe” or “none” regarding dysmenorrhea or nonmenstrual pelvic pain (NMPP) from a Wilcoxon rank sum test. Number of days is equal to the number of days the subject reported dysmenorrhea or NMPP as none, mild, moderate, or severe. Missing dysmenorrhea with nonmissing NMPP or missing NMPP with nonmissing dysmenorrhea are imputed as zero days. Percentage of days is equal to the number of days the subject reported dysmenorrhea or NMPP divided by the number of days she answered the e-diary, multiplied by 100. Baseline is defined as the average of the last 35 days prior to and including the first dosing date.

Figure 3

Percent of nonmenstrual pelvic pain responders by bleeding status. Responder equals reduced nonmenstrual pelvic pain and reduced or stable rescue analgesic use. p