Predictors of response for elagolix with add-back therapy in women with heavy menstrual bleeding associated with uterine fibroids.

BACKGROUND: Uterine fibroids are one of the most common neoplasms found among women globally, with a prevalence of approximately 11 million women in the United States alone. The morbidity of this common disease is significant because it is the leading cause of hysterectomy and causes significant functional impairment for women of reproductive age. Factors including age, body mass index, race, ethnicity, menstrual blood loss, fibroid location, and uterine and fibroid volume influence the incidence of fibroids and severity of symptoms. Elagolix is an oral gonadotropin-releasing hormone receptor antagonist that competitively inhibits pituitary gonadotropin-releasing hormone receptor activity and suppresses the release of gonadotropins from the pituitary gland, resulting in dose-dependent suppression of ovarian sex hormones, follicular growth, and ovulation. In Elaris Uterine Fibroids 1 and Uterine Fibroids 2, 2 replicate multicenter, double-blind, randomized, placebo-controlled, phase 3 studies, treatment of premenopausal women with elagolix with hormonal add-back therapy demonstrated reduction in heavy menstrual bleeding associated with uterine fibroids.
OBJECTIVE: This analysis aimed to evaluate the safety and efficacy of elagolix (300 mg twice a day) with add-back therapy (1 mg estradiol/0.5 mg norethindrone acetate once a day) in reducing heavy menstrual bleeding associated with uterine fibroids in various subgroups of women over 6 months of treatment. STUDY
DESIGN: Data were pooled from Elaris Uterine Fibroid-1 and Uterine Fibroid-2 studies, which evaluated premenopausal women (18-51 years) with heavy menstrual bleeding (>80 mL menstrual blood loss per cycle, alkaline hematin methodology) and ultrasound-confirmed uterine fibroid diagnosis. Subgroups analyzed included age, body mass index, race, ethnicity, baseline menstrual blood loss, fibroid location, and uterine and primary fibroid volume (largest fibroid identified by ultrasound). The primary endpoint was the proportion of women with <80 mL menstrual blood loss during the final month and ≥50% menstrual blood loss reduction from baseline to final month. Secondary and other efficacy endpoints included mean change in menstrual blood loss from baseline to final month, amenorrhea, symptom severity, and health-related quality of life. Adverse events and other safety endpoints were monitored.
RESULTS: The overall pooled Elaris Uterine Fibroid-1 and Uterine Fibroid-2 population was typical of women with fibroids, with a mean age of 42.4 (standard deviation, 5.4) years and a mean body mass index of 33.6 (standard deviation, 7.3) kg/m2 and 67.6% of participants being black or African American women. A wide range of baseline uterine and fibroid volumes and menstrual blood loss were also represented in the overall pooled study population. In all subgroups, the proportion of responders to the primary endpoint, mean change in menstrual blood loss, amenorrhea, reduction in symptom severity, and improvement in health-related quality of life were clinically meaningfully greater for women who received elagolix with add-back therapy than those who received placebo and consistent with the overall pooled study population for the primary endpoint (72.2% vs 9.3%), mean change in menstrual blood loss (-172.5 mL vs -0.8 mL), amenorrhea (50.4% vs 4.5%), symptom severity (-37.1 vs -9.2), and health-related quality of life score (39.9 vs 8.9). Adverse events by subgroup were consistent with the overall pooled study population.
CONCLUSION: Elagolix with hormonal add-back therapy was effective in reducing heavy menstrual bleeding associated with uterine fibroids independent of age, body mass index, race, ethnicity, baseline menstrual blood loss, fibroid location, and uterine and primary fibroid volume.

Introduction

Uterine fibroids are the most common neoplasms found among women globally, with a prevalence of approximately 11 million women in the United States.[1-3] Uterine fibroids cause significant morbidity in 25% to 50% of affected women.[4] The most common symptoms include heavy menstrual bleeding, which occurs in 46% to 59% of symptomatic women and can lead to anemia and fatigue; reproductive dysfunction; and bulk symptoms including bowel and bladder dysfunction, pelvic pain, and abdominal protrusion.[2,5,6]

Factors including race, ethnicity, fibroid location, uterine and fibroid volume, age, and body mass index (BMI) influence the incidence of fibroids and symptom severity.[7-14] Race and ethnicity are key risk factors for uterine fibroids.[4] African American women have a 3-fold greater incidence and relative risk of uterine fibroids, and disease onset occurs 10 to 15 years earlier than in women of other races.[9] In addition, women of Latino descent have a 1.3-fold increase in risk of uterine fibroids compared with non-Latina women.[10]

Fibroid location and uterine and fibroid volume have been shown to be associated with severity of heavy menstrual bleeding. Submucosal or International Federation of Gynecology and Obstetrics (FIGO) classification system types 0 to 3 fibroids are thought to be the main contributors to heavy menstrual bleeding, with intramural fibroids (FIGO type 4) contributing more than subserosal or cervical ones (FIGO types 5–8).[13-17] Various studies have also shown that even small fibroids can be associated with heavy menstrual bleeding, with an increased risk as fibroid size increases.[14]

Uterine fibroid incidence increases with age until menopause, and symptoms most often resolve after menopause.[7,18] The relationship between BMI and uterine fibroids is mixed, with some studies finding correlations between BMI and uterine weight with fibroids[8] and others demonstrating that weight gain is positively associated with the risk of fibroids only among women with a history of pregnancy.[19]

In addition to contributing to the risk of uterine fibroids, the aforementioned factors also traditionally influence treatment decisions for the disease.[20,21] Multiple treatment options exist for fibroids, including hysterectomy, myomectomy, myolysis, uterine artery embolization, and medical management. Moreover, most women who seek treatment for symptomatic uterine fibroids prefer an alternative to surgery.[22]

Long-term medical therapy specifically for the treatment of heavy menstrual bleeding associated with uterine fibroids is currently unavailable in the United States. Recently, the efficacy of oral gonadotropin-releasing hormone (GnRH) antagonists in reducing heavy menstrual bleeding associated with uterine fibroids has been studied in clinical trials, with GnRH antagonists being considered as potentially long-term treatment options.[23]

Elagolix is an oral GnRH receptor antagonist that competitively inhibits pituitary GnRH receptor activity and suppresses pituitary release of gonadotropins, resulting in a dose-dependent suppression of ovarian sex hormones, follicular growth, and ovulation, without the initial flare effects seen with GnRH agonists.[24,25] Hormonal add-back therapy coadministered with elagolix attenuates hypoestrogenic effects.[25] In 2 replicate multicenter, double-blind, randomized, placebo-controlled, phase 3 studies, Elaris Uterine Fibroids 1 (UF-1) and Uterine Fibroids 2 (UF-2), elagolix with hormonal add-back therapy demonstrated reduction in heavy menstrual bleeding associated with uterine fibroids over 6 months of treatment, with statistically significant reductions in menstrual blood loss as early as 1 month of treatment.[23] This analysis evaluates the efficacy in reducing heavy menstrual bleeding associated with uterine fibroids and the safety of elagolix with hormonal add-back therapy in subgroups that include age, BMI, race, ethnicity, baseline menstrual blood loss, fibroid location, and uterine and primary fibroid volume.

Materials and Methods

Study design

Data were pooled from 2 replicate multicenter, double-blind, randomized, placebo-controlled, phase 3 studies, Elaris UF-1 and UF-2, previously published by Schlaff et al.[23] One patient in UF-1 and 3 patients in UF-2 who underwent randomization were enrolled before the trial registration date on ClinicalTrials.gov because of an administrative error. Premenopausal women aged 18 to 51 years at the time of screening with heavy menstrual bleeding demonstrated by >80 mL of menstrual blood loss per menstrual cycle for at least 2 separate cycles as measured by the alkaline hematin method and pelvic ultrasound (transabdominal or transvaginal)–confirmed uterine fibroid diagnosis were included in the studies. Inclusion and exclusion criteria, as well as patient disposition, were previously reported.[23]

Both clinical trials used a washout period of hormone therapies (if applicable), a screening period of 2.5 to 3.5 months, and a treatment period of 6 months. Women started treatment within 10 days of the start of their menses and were randomly assigned in a 2:1:1 ratio to elagolix 300 mg twice daily with hormonal add-back therapy (estradiol 1 mg/norethindrone acetate 0.5 mg once daily), elagolix 300 mg twice daily alone, or placebo in a matched, double-blind manner. Elagolix alone was included only as a reference arm to characterize the effect of add-back therapy on the safety or tolerability of elagolix. Therefore, the focus of this subgroup analysis was on elagolix with add-back therapy, as compared with placebo.

The trials were conducted in accordance with the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use guidelines and applicable regulations and ethical principles of the Declaration of Helsinki. The study protocols were approved by the Schulman Institutional Review Board for central sites and by an institutional review board or ethics committee for all other study sites. All women provided written, informed consent.

Efficacy endpoints and safety assessments

The primary, secondary, and other efficacy endpoints described here assessed the treatment effect of elagolix with hormonal add-back therapy across key variables potentially affecting efficacy. Demographic subgroups analyzed for all key endpoints included age, BMI, race, and ethnicity. Disease severity subgroups based on baseline characteristics included menstrual blood loss, FIGO classification, uterine volume, and primary fibroid volume. Uterine Fibroid Symptom and Health-Related Quality of Life (UFS-QOL) scores were analyzed for the following subgroups: age, BMI, race, menstrual blood loss, FIGO classification, uterine volume, and primary fibroid volume. Uterine volume and primary fibroid volume, defined at baseline as the fibroid with the largest volume, were measured by ultrasound. All ultrasound images were read by independent central reviewers (Parexel International Corporation, Waltham, MA). Median values used to define subgroups were based on the overall median of the pooled Elaris UF-1 and UF-2 data set.

At baseline, fibroids were grouped by the following FIGO types for location: 0–3, 4, and 5–8.[13] The analyses were completed for (1) lowest FIGO type, (2) highest FIGO type, and (3) FIGO type for the primary fibroid. These 3 subgroups were identified to account for bleeding contributed by submucosal fibroids (lower FIGO types), subserosal fibroids (higher FIGO types), and primary fibroids. Although patients with fibroids characterized as FIGO 0 were excluded during screening, 13 patients from Elaris UF-1 and UF-2 were classified as FIGO 0 at baseline. These women were allowed to continue in the study as they were eligible at the time of screening.

Clinically meaningful reduction in menstrual blood loss was measured by the primary efficacy endpoint, which was the proportion of women who had both <80 mL of menstrual blood loss during the final month and ≥50% reduction in menstrual blood loss from baseline to final month. The mean change from baseline in menstrual blood loss to final month was a secondary endpoint, and the other efficacy endpoint was the proportion of women who achieved amenorrhea at the final month. The final month was defined as the last 28 days before and including the last treatment period visit date (if data on menstrual blood loss [measured with the use of the alkaline hematin method] that could be evaluated were available between the last treatment period visit date and the last dose date, then the last dose date was used). All bleeding endpoints were objectively measured using the alkaline hematin method.[26]

Changes from baseline to month 6 in the UFS-QOL questionnaire scores were also analyzed. The 4-week recall version of the UFS-QOL questionnaire includes a symptom severity score and a health-related quality of life (HRQoL) total score that is the sum of 6 subscale scores: concern, activities, energy/mood, control, self-conscious, and sexual function.[27] For symptom severity, scores ranged from 0 to 100, with higher scores indicating increased severity; for HRQoL total and subscales, scores ranged from 0 to 100, with higher scores indicating better quality of life.[28]

Treatment-emergent adverse events were assessed by subgroup and the overall pooled study population.

Statistical analysis

Within each level of a subgroup, analysis for the primary efficacy endpoint consisted of a logistic regression with the responder as the response variable, baseline menstrual blood loss volume as a covariate, and treatment and study as the main effects. Women who prematurely discontinued the study drug use because of “lack of efficacy,” “requires surgery or invasive intervention for treatment of uterine fibroids,” or adverse events were considered as nonresponders, regardless of whether the 2 conditions were met or not.

Statistical analyses for the secondary and other endpoints and sensitivity analyses of the primary endpoint were previously described.[23] Adverse events were summarized based on MedDRA (International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use, Geneva, Switzerland) version 21.0. The Breslow-Day test was used to examine the homogeneity of treatment effect for each event type overall and only if there were at least 10 subjects per treatment group with an event within each subgroup.

SAS software (version 9.4, SAS Institute, Cary, NC), with a 2-sided significance level of .05 and a confidence interval (CI) of 95%, was used to perform statistical analyses. Missing final month menstrual blood loss data were imputed using multiple imputation.

Results

A total of 791 women were randomized in the Elaris UF-1 and UF-2 studies, with 790 treated and 617 (78.0%) completing the treatment period. This overall pooled study population was typical of women with uterine fibroids: most women were black or African American (67.6%), the mean age was 42.4 years (SD, 5.4), and the mean BMI was 33.6 kg/m2 (SD, 7.3).[23] Furthermore, most women in the overall pooled study population had multiple fibroids, and broad ranges of baseline menstrual blood loss volume (83.8–1207.1 mL), uterine volume (71.6–3347.9 cm3), and primary fibroid volume (1.0–1081.5 cm3) were represented.[23] No notable differences were observed among the baseline characteristics of the overall pooled study population and all patient demographic and disease severity subgroups (Supplemental Table 1).

Primary efficacy endpoint

The efficacy of elagolix with add-back hormonal therapy compared with placebo was maintained across all subgroups (Figure 1 and Supplemental Figure 1). The proportion of women in each subgroup who achieved the primary endpoint was considerably greater with elagolix with add-back (range, 59%–80%) than placebo (range, 4%–16%), consistent with the overall pooled study population (placebo, 9%; elagolix with add-back, 72%) (Supplemental Figure 2). The odds ratios (ORs) for elagolix with add-back were numerically higher in women with larger uteri (≥median, 42.8; 95% CI, 16.615–110.318;

FIGURE 1

Odds ratios for primary endpoint by factors contributing to disease severity

The odds ratios with 95% CIs are shown graphically and listed in the table to the right for each disease severity subgroup treated with elagolix with add-back. Odds ratios were determined by pooling the results from a logistic regression model including treatment and study as the main effects and baseline menstrual blood loss volume as a covariate in each data set from multiple imputation under each subgroup level. Median values for uterine and primary fibroid volumes were based on the overall median of the pooled Elaris Uterine Fibroids 1 and Uterine Fibroids 2 data set.

CI, confidence interval; E2, estradiol; FIGO, International Federation of Gynecology and Obstetrics; NETA, norethindrone acetate.

Menstrual blood loss

There was a statistically significant reduction in mean menstrual blood loss volume from baseline to final month with elagolix with add-back vs placebo in all subgroups (Table 1 and Supplemental Table 2). The change in mean menstrual blood loss in the elagolix with add-back group ranged from −206.4 mL (standard error [SE], 16.7) to −140.9 mL (SE, 10.6), whereas mean menstrual blood loss in the placebo group ranged from −34.4 mL (SE, 19.1) to 25.7 mL (SE, 25.2). This result was similar to the change in mean menstrual blood loss from baseline to final month with elagolix with add-back (−172.5 mL; SE, 7.6) and placebo (−0.8 mL; SE, 10.8) in the overall pooled study population (Table 1).

TABLE 1

Change in MBL from baseline to final month by disease severity subgroup

Factors	Subgroup/treatment	N	Change from baseline in MBL volume to final month, mL (SE)	Difference from placebo, mL (SE)	P value
Overall pooled study population	Placebo	196	−0.8 (10.8)	—	—
	Elagoli+E2/NETA	395	−172.5 (7.6)	−171.7 (13.1)	<.001
Lowest FIGO type classification	0–3
	Placebo	45	−5.9 (25.0)
	Elagolix+E2/NETA	95	−206.4 (16.8)	−200.5 (30.2)	<.001
	4
	Placebo	110	11.8 (14.5)
	Elagolix+E2/NETA	225	−163.3 (10.2)	−175.2 (17.7)	<.001
	5–8
	Placebo	37	−32.8 (20.3)
	Elagolix+E2/NETA	69	−158.2 (14.7)	−125.4 (25.3)	<.001
Highest FIGO type classification	0–3
	Placebo	25	−0.7 (26.9)
	Elagolix+E2/NETA	47	−191.6 (18.2)	−190.9 (32.7)	<.001
	4
	Placebo	85	0.3 (16.1)
	Elagolix+E2/NETA	177	−177.0 (11.4)	−177.3 (19.8)	<.001
	5–8
	Placebo	82	−4.7 (17.3)
	Elagolix+E2/NETA	165	−162.5 (12.1)	−157.8 (21.2)	<.001
Primary fibroid FIGO classification	0–3
	Placebo	38	−7.0 (22.3)
	Elagolix+E2/NETA	78	−216.5 (15.0)	−209.5 (26.9)	<.001
	4
	Placebo	96	5.8 (16.3)
	Elagolix+E2/NETA	191	−173.9 (11.8)	−179.7 (20.1)	<.001
	5–8
	Placebo	58	−16.2 (18.2)
	Elagolix+E2/NETA	120	−142.8 (12.6)	−126.6 (22.3)	<.001
Uterine volume (median=356.5 cm3)	<Median
	Placebo	88	−1.3 (15.7)
	Elagolix+E2/NETA	203	−142.8 (10.3)	−141.5 (18.6)	<.001
	≥Median
	Placebo	108	−3.1 (14.5)
	Elagolix+E2/NETA	192	−203.2 (10.9)	−200.1 (18.2)	<.001
Primary fibroid volume (median=36.2 cm3)	<Median
	Placebo	92	−23.0 (15.2)
	Elagolix+E2/NETA	189	−140.9 (10.6)	−117.9 (18.4)	<.001
	≥Median
	Placebo	100	19.3 (15.2)
	Elagolix+E2/NETA	200	−202.2 (10.7)	−221.6 (18.7)	<.001

Data are least-squares mean (SE).

Median values for uterine and primary fibroid volumes were based on the overall median of the pooled Elaris UF-1 and UF-2 data set.

Final month was defined as the last 28 days before and including the reference day.

Missing final month MBL was imputed using multiple imputation (subset of the data sets obtained by multiple imputation for the primary analysis for subjects with baseline disease severity).

Statistical significance was determined for the difference between the elagolix with add-back dose group and placebo by pooling the results from a logistic regression model including treatment and study as the main effects and baseline MBL volume as a covariate in each data set from multiple imputation.

E2, estradiol; FIGO, International Federation of Gynecology and Obstetrics; MBL, menstrual blood loss; NETA, norethindrone acetate; SE, standard error; UF-1, Uterine Fibroids 1; UF-2, Uterine Fibroids 2.

Amenorrhea

The proportion of women in each subgroup who achieved amenorrhea at the final month with elagolix with add-back (range, 44.3%–59.7%) was statistically significantly greater than placebo (range, 0.0%–15.8%) and consistent with the results of the overall pooled study opulation (elagolix with add-back: 50.4%; 95% CI, 45.2–55.6 vs placebo: 4.5%; 95% CI, 1.5–7.6) (Supplemental Table 3). In addition, the ORs for elagolix with add-back were consistent across the subgroups.

Symptom severity and health-related quality of life

Among all subgroups, the mean change in symptom severity score from baseline to month 6 in the elagolix with add-back treatment group (range, −42.3 to −33.3) was statistically significantly greater than the mean change in the placebo group (range, −14.6 to −1.4) (Figure 2, A, and Supplemental Figure 3, A). Similarly, the mean change in HRQoL total score from baseline to month 6 in the elagolix with add-back treatment group (range, 36.6–43.5) was statistically significantly greater than the mean change in the placebo group (range, 2.4–14.1) among all subgroups (Figure 2, B, and Supplemental Figure 3, B). Similar results were also seen among all subgroups for each of the 6 UFS-QOL subscales (Supplemental Tables 5–10). The UFS-QOL results for each of the subgroups were consistent with the results from the overall pooled study population (Figure 2 and Supplemental Figure 3; Supplemental Tables 4–10).

FIGURE 2

Mean changes in UFS-QOL scores from baseline to month 6 for disease severity subgroups

A, The mean change in symptom severity score for each subgroup is depicted. B, The mean change in total HRQoL score for each subgroup is depicted. For symptom severity, a higher score indicates worse symptom severity. For HRQoL, a higher score indicates better quality of life. Data are presented as LS means, with error bars representing the standard error of mean. The change from baseline to month 6 in each parameter was analyzed using an analysis of covariance model with treatment as the main effect and baseline value as a covariate. Median values for uterine and primary fibroid volumes were based on the overall median of the pooled Elaris Uterine Fibroids 1 and Uterine Fibroids 2 data set. The asterisk symbol (***) indicates P<.001.

FIGO, International Federation of Gynecology and Obstetrics; HRQoL, health-related quality of life; LS, least-squares; UFS-QOL, Uterine Fibroid Symptom and Health-Related Quality of Life.

Safety

Adverse events were described for each demographic and disease severity subgroup. The percentages of women treated with elagolix with add-back who reported at least 1 adverse event appeared similar among all subgroups, and most adverse events were classified as mild or moderate, consistent with previous results reported in Schlaff et al[23] (Supplemental Tables 11 and 12).

Structured Discussion or Comment

Principal findings

This subgroup analysis demonstrated that treatment with elagolix with hormonal add-back therapy is efficacious in reducing heavy menstrual bleeding, achieving amenorrhea, and improving severity of symptoms and HRQoL in women across all ages and BMIs, various race and ethnicity groups, and over a wide range of baseline menstrual blood loss volume and uterine anatomy parameters.

Clinical implications

These study results show that response to elagolix with add-back therapy is not diminished by clinical or uterine factors that indicate more severe disease. Thus, all women may benefit from medical therapy before resorting to surgery.

Hysterectomy is the long-standing primary management option for symptomatic fibroids; however, it is not without a loss of fertility and surgical complications.[22] In addition, hysterectomy, even with conservation of both ovaries, has also been linked to long-term cardiovascular risks.[29] Despite the risks associated with hysterectomy, many women are not offered alternatives to hysterectomy for the treatment of heavy menstrual bleeding associated with uterine fibroids.[30]

Current medical management options used for symptomatic uterine fibroids include nonhormonal treatments such as nonsteroidal antiinflammatory drugs and antifibrinolytics and hormonal options, such as combination oral contraceptives, levonorgestrel-releasing intrauterine systems, progestogens, and GnRH agonists. In Canada and Europe, ulipristal acetate is also available; however, although effective, it is indicated for only 1 treatment course unless the patient is not a surgical candidate. Treatment breaks and monitoring are also required.[21,31] Current options for medical treatment of symptomatic fibroids have been shown to produce inconsistent results across subsets of women. Furthermore, such options are only approved in the United States for short-term presurgical treatment of women who experience anemia associated with fibroid-related heavy menstrual bleeding.

Further adding to the challenge of medical management of heavy menstrual bleeding associated with uterine fibroids is a paucity of literature on the medical management of different subgroups of women with uterine fibroids and a lack of randomized trials comparing various treatment options.[32] A recent report from the Agency for Healthcare Research and Quality guidance on fibroid management showed that there is little evidence for individualized management.[33] This subgroup analysis aims to close this gap.

Historically, factors such as uterine and fibroid volume, fibroid location, and age have been used to exclude women from medical therapy. Data from this study support the contention that all women should be offered a medical trial for the treatment of heavy menstrual bleeding associated with fibroids to allow women to choose from all available, effective treatment options.[32] This study provides information in an area with limited data and demonstrated that regardless of patient demographics and disease phenotype, elagolix with add-back therapy was effective at reducing heavy menstrual bleeding.

Treatment with elagolix with add-back therapy also demonstrated significantly decreased symptom severity and improved HRQoL in all subgroups of women. Treatment with elagolix with add-back resulted in UFS-QOL scores similar to those of women without uterine fibroids (symptom severity, 22.5; SD, 21.1; HRQoL total score, 86.4; SD, 17.7).[28] Moreover, changes of 9 to 15 points in UFS-QOL are considered to be clinically meaningful, a target achieved across subgroups in this study (Figure 2 and Supplemental Figure 3; Supplemental Tables 4–10).

Research implications

It has been hypothesized that submucosal fibroids contribute to heavy menstrual bleeding; by extension, the further away the fibroid is from the endometrial cavity, the less likely it will be to contribute to bleeding. However, studies have demonstrated that regardless of location, fibroids are biologically active tissues that produce vasoactive and other regulatory factors that can alter the endometrium in a paracrine manner.[34-36] The consistent baseline mean menstrual blood loss (Supplemental Table 1) and efficacy of elagolix with add-back therapy across all fibroid locations by FIGO classification (Figure 1 and Supplemental Figure 2), which demonstrate reduction of heavy menstrual bleeding independent of location in this study, may support the paracrine effect of fibroids.

Strengths and limitations

Women who are at the highest risk for fibroids or who exhibit the most severe symptoms and thus are most likely to be encountered in everyday clinical practice were represented in this study. Although the study was limited by smaller sample sizes for a few of the subgroups, considerable or statistically significant results were still achieved for key endpoints.

Conclusions

Elagolix with hormonal add-back therapy, an oral medical therapy for the treatment of heavy menstrual bleeding associated with uterine fibroids, appears effective across all patient demographics and disease phenotypes and shows a trend to work better with more extensive disease. This broad efficacy opens the door for new ways of thinking regarding patient selection for longer term medical management of women with heavy menstrual bleeding associated with fibroids who previously may not have been offered medical management, only surgical intervention.

Data Sharing

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These clinical trial data can be requested by any qualified researchers who engage in rigorous, independent scientific research and will be provided following review and approval of a research proposal and Statistical Analysis Plan and execution of a Data Sharing Agreement. Data requests can be submitted at any time, and the data will be accessible for 12 months, with possible extensions considered. For more information on the process, or to submit a request, visit the following link: https://www.abbvie.com/our-science/clinical-trials/clinical-trials-data-and-information-sharing/data-and-information-sharing-with-qualified-researchers.html.