Changes in symptom burden and quality of life among women with uterine fibroids receiving relugolix combination therapy: a plain language summary

What is this summary about? This is a summary of findings from two research studies (known as clinical trials). The studies looked at how well a medicine called relugolix combination therapy worked in women with heavy menstrual bleeding (heavy bleeding during a period) with uterine fibroids (noncancerous or benign growths in the uterus). In this analysis of the studies, researchers looked at how patients self-reported their uterine fibroid symptoms before and after taking relugolix combination therapy. Researchers also looked at how patients self-reported the impact of uterine fibroids on their health-related quality of life before and after taking relugolix combination therapy. What were the results? Women took either relugolix combination therapy or placebo (a pill that contains no medicine) by mouth once daily for 24 weeks. Women completed the Uterine Fibroid Symptom and Quality of Life questionnaire (where “quality of life” refers to the women's health-related quality of life related to uterine fibroids) before, during, and after treatment. The questionnaire let researchers see if the women felt that relugolix combination therapy decreased the burden of uterine fibroid symptoms and improved the women's health-related quality of life related to uterine fibroids. More women said that they felt less distress due to their uterine fibroid symptoms and that their health-related quality of life related to uterine fibroids was better after taking relugolix combination therapy compared with women who took placebo. What do the results mean? Relugolix combination therapy may lessen distress associated with uterine fibroid symptoms and improve health-related quality of life related to uterine fibroids.

Plain Language Summary of Publication Stewart, Lukes, Venturella and co-authors

What is relugolix combination therapy?
What are uterine fibroids?
Uterine fibroids are non-cancerous (meaning not cancer or benign) growths in the uterus (or womb).
About 1 out of 4 (or 25%) women with uterine fibroids have symptoms (such as heavy menstrual bleeding or pain) that need treatment.About 3 out of 4 (or 75%) premenopausal women (those still having menstrual periods) have uterine fibroids.
Many do not have symptoms.
Impacts of symptoms include depression, social isolation, feelings of helplessness, and increased anxiety.
Uterine fibroids can also affect a woman's social and family life and the ability to work or go to school.
Overall, the symptoms of uterine fibroids cause limitations in womens' physical activities and social life, as well as impact their energy levels, self-consciousness, sexual function and other aspects of daily life.

Who is this article for?
This summary is written to help patients with uterine fibroids, their families, and their healthcare providers understand how relugolix combination therapy impacted patients' uterine fibroids symptoms and health-related quality of life related to uterine fibroids during two research studies.
One tablet of relugolix combination therapy contains:

mg
Relugolix, which is a medicine taken by mouth that can lower the levels of certain sex hormones (chemical messengers in the body) that lead to uterine fibroid growth.
This could ease uterine fibroid symptoms.

Low doses of 2 hormones
Norethindrone acetate, which protects the uterus from the e ffects of taking estrogen alone 0.5 mg Estradiol, which is a type of estrogen (a sex hormone) that reduces the risk of bone loss from taking relugolix alone 1 mg 10.57264/cer-2023-0194 QoL among women with uterine fibroids receiving relugolix therapy

Plain Language Summary of Publication
What did researchers ask in this analysis?
About 3 out of 4 (or 75%) premenopausal women (those still having menstrual periods) have uterine fibroids.
Many do not have symptoms.
How did researchers ask these questions?
Researchers asked the following questions for this analysis: Compared with placebo (a pill that contains no medicine and is taken in the same manner as the study medicine): How severe was the burden of uterine fibroid symptoms?How much did women think that relugolix combination therapy reduced their distress from symptoms of uterine fibroids?
How much did women think their health-related quality of life related to uterine fibroids changed after taking relugolix combination therapy?
Burden, including distress, from uterine fibroid symptoms?
Health-related quality of life related to uterine fibroids?
• Women received either relugolix combination therapy or placebo once each day for 24 weeks (or about 6 months).
• Other measures, including safety and the e ffects of treatment on pain and menstrual bleeding, were evaluated in the same studies; they are not discussed in this summary but are published elsewhere.For further information, please see the web links provided in the section: Where can readers find more information on these studies?
Women were asked to answer a questionnaire called the Uterine Fibroid Symptom and Quality of Life Questionnaire ?
The questionnaire is broken down into sets of questions.These sets focus on different ways uterine fibroid symptoms affect the women and how much their health-related quality of life related to uterine fibroids is affected.
How much distress do you experience due to your symptoms?
How much are your concerns, activities, energy or mood, control, self-consciousness, and sexual function affected?

Health-related quality of life related to uterine fibroids
What happened in this analysis?

Who took part in this analysis?
All the women who took part were: Women answered the questionnaire before treatment, after 12 weeks of treatment (about 3 months), and after 24 weeks of treatment (about 6 months)

Researchers then calculated how much the participant's scores changed from before treatment to after treatment
The changes in scores helped researchers to understand how much the women thought their treatment affected their uterine fibroid symptoms and their health-related quality of life related to uterine fibroids by comparing these changes with those in women treated with placebo.
Researchers compared the women's responses before treatment and aft er 24 weeks of treatment.
Researchers scored the participants' answers.
Questions for uterine fibroid symptom severity • Higher scores mean higher levels of distress due to uterine fibroid symptoms including bleeding and pain Questions for health-related quality of life related to uterine fibroids

What was self-reported in this analysis?
Women self-reported how much they felt distressed by uterine fibroid symptoms before starting treatment: "Not at all distressed" to "A very great deal" 100 0 Higher scores indicate a higher level of distress due to uterine fibroid symptoms

to 60
Women self-reported how often symptoms of uterine fibroids impacted their daily life before starting treatment: "All of the time" to "None of the time" 100 0 Higher scores indicate better health-related quality of life related to uterine fibroids What were the main findings of this analysis?

Health
Higher scores indicate a higher level of distress due to uterine fibroid symptoms; decreasing scores indicate decreasing levels of distress

Relugolix combination therapy worked better than placebo at lowering scores for distress from uterine fibroids
Higher scores indicate better health-related quality of life related to uterine fibroids Women who received relugolix combination therapy reported reduced distress due to uterine fibroid symptoms more than those who took placebo.

Relugolix combination therapy Placebo
Before treatment

A fter 12 weeks of treatment A fter 24 weeks of treatment
Women taking relugolix combination therapy had better health-related quality of life related to uterine fibroids than women taking placebo.Women taking relugolix combination therapy had higher scores for health-related quality of life related to uterine fibroids for various aspects of daily life compared with women taking placebo.

Relugolix combination therapy Placebo
Relugolix combination therapy worked better than placebo at increasing scores for health-related quality of life related to uterine fibroids for various aspects of daily life

What do the results of the analysis mean?
• Compared with placebo, participants who received relugolix combination therapy had: -Lower uterine fibroid symptom severity scores, meaning they had reduced distress from their symptoms -Higher scores for health-related quality of life related to uterine fibroids.This included level of concern, daily activities, energy and mood, feeling of control, self-consciousness, and sexual function -The greatest reported improvements in health-related quality of life related to uterine fibroids were within the areas of concern and daily activities • Improvement of uterine fibroid-associated symptoms with relugolix combination therapy may help to: -Decrease levels of distress due to symptoms -Improve health-related quality of life related to uterine fibroids Who sponsored this study?
The studies used for this analysis (LIBERTY 1 and LIBERTY 2) were sponsored by Myovant Sciences GmbH (now Sumitomo Pharma Switzerland GmbH).Where can readers find more information about this study?
Original article: The original article, 'Quality of life with relugolix combination therapy for uterine fibroids: LIBERTY randomized trials', was published in the American Journal of Obstetrics and Gynecology (Stewart EA, et al. Am. J. Obstet. Gynecol. 228:320 e1-320.e11 [2023]).
• You can read the full article at: https://www.ajog.org/article/S0002-9378(22)02166-4/fulltext • You can read the full article about the main findings from the LIBERTY 1 and LIBERTY 2 studies at: https://www.nejm.org/doi/10.1056/NEJMoa2008283 • You can read the plain language summary about the main findings from the LIBERTY 1 and LIBERTY 2 studies at: https://www.tandfonline.com/doi/abs/10.2217/pmt-2022-0085 Trial registration site: You can read more about the studies used for this analysis (LIBERTY 1 and LIBERTY 2) at the following trial registration websites: • LIBERTY 1 study: https://www.clinicaltrials.gov/ct2/show/NCT03049735 • LIBERTY 2 study: https://www.clinicaltrials.gov/ct2/show/NCT03103087 -For more information on clinical studies in general, please visit: https://www.clinicaltrials.gov/ct2/about-studies/learn 18 to 50 years old Diagnosed with uterine fibroids and had heavy bleeding during their menstrual periods* Premenopausal (still having menstrual periods) *Heavy bleeding during menstrual periods was considered menstrual blood loss of about one-third of a cup (80 ml) per cycle for two cycles or about two-thirds of a cup (160 ml) during one cycle worked better than placebo at increasing scores for health-related quality of life related to uterine fibroidsAfter 24 weeks, scores for healthrelated quality of life related to uterine fibroids showed:10.57264/cer-2023-0194QoLamong women with uterine fibroids receiving relugolix therapyPlain Language Summary of PublicationHigher scores indicate better health-related quality of life related to uterine fibroids

-related quality of life related to uterine fibroids score range 36 to 38 509 women
(entered the study between April 2017 and July 2019)

to 1 cup Both groups had similar characteristics at the start of the studies. About 5% were American Indian or Alaska Native, Asian, Other, multiple, or unreported Scores for uterine fibroid symptom severity and health-related quality of life related to uterine fibroids before starting treatment Uterine fibroid symptom severity score range 10
.57264/cer-2023-0194 J.Comp.Eff.Res.(2023)e230194Plain Language Summary of Publication Stewart, Lukes, Venturella and co-authors Plain Language Summary of Publication Stewart, Lukes, Venturella and co-authors