Appendix B
NATIONAL INSTITUTE FOR HEALTH AND CARE EXCELLENCE
Health Technology Appraisal
Relugolix with oestradiol and norethindrone acetate for treating uterine
fibroids
Final scope
Remit/appraisal objective
To appraise the clinical and cost effectiveness of relugolix with oestradiol and
norethindrone acetate within its marketing authorisation for treating uterine fibroids.
Background
Uterine fibroids are noncancerous growths of the uterus. The exact cause of fibroids
is not known, but they have been linked to the hormone oestrogen.1 Most are
asymptomatic, but they can cause significant morbidity. The most common symptom
of uterine fibroids is heavier than normal or prolonged menstrual bleeding. Other
symptoms include pelvic pressure or pain, frequent urination, constipation and pain
or discomfort during sex. In rare cases, complications with fibroids can interfere with
pregnancy or cause infertility.1 The type and severity of symptoms is influenced by
the location, size and number of fibroids.2 Fibroids are generally classified by their
location. Intramural fibroids grow within the muscular uterine wall. Submucosal
fibroids grow in the muscle layer beneath the uterus’s inner lining and grow into the
uterine cavity. Subserosal fibroids develop outside of the uterus and grow into the
pelvis.
Fibroids usually develop during the reproductive years (from around 16 to 50 years)
when oestrogen levels are at their highest.1 The prevalence of symptomatic fibroids
is low in women younger than 30 years but is between 20 to 50% in women older
than 30 years.3 Risk factors for uterine fibroids include race, family history of fibroids,
age and obesity.4
Oestrogen and progesterone control the proliferation and maintenance of uterine
fibroids. Most medical treatments act by interfering with their production or function.4
For people with uterine fibroids less than 3 cm in diameter and not causing distortion
of the uterine cavity, NICE guideline 88 (NG88) recommends considering a
levonorgestrel-releasing intrauterine system (LNG-IUS) for the treatment of heavy
menstrual bleeding. If heavy menstrual bleeding worsens or an LNG-IUS is not
suitable, pharmacological treatments (such as tranexamic acid and non-steroidal
anti-inflammatory drugs) and hormonal treatments (such as combined hormonal
contraception, cyclical oral progestogens and gonadotrophin-releasing hormone
analogues) are recommended. Surgery (second-generation endometrial ablation or
hysterectomy) is recommended as an option if treatment is unsuccessful or declined,
or symptoms are severe. For people with submucosal uterine fibroids less than 3 cm
in diameter hysteroscopic removal should be considered. For people with uterine
fibroids of 3 cm or more in diameter, the same pharmacological and surgical
treatments are recommended as options as well as uterine artery embolisation and
myomectomy. Pretreatment with a gonadotrophin-releasing hormone analogue
before hysterectomy and myomectomy should be considered if uterine fibroids are
causing an enlarged or distorted uterus.
Final scope for the appraisal of relugolix with oestradiol and norethindrone acetate for treating
uterine fibroids
Issue Date: April 2021 Page 1 of 4
© National Institute for Health and Care Excellence 2021. All rights reserved.
Appendix B
The technology
Relugolix (Ryeqo, Gedeon Richter) is a small molecule that binds to the
gonadotrophin-releasing hormone receptor in the pituitary gland, decreasing the
downstream production of oestrogen and progesterone by the ovaries. It is
administered orally, in combination with oestradiol and norethindrone acetate.
Relugolix does not currently have a marketing authorisation in the UK for treatment of
uterine fibroids. It has been studied in clinical trials in combination with oestradiol and
norethindrone acetate compared with placebo in premenopausal women aged 18 to
50 years old with heavy menstrual bleeding associated with uterine fibroids.
Intervention(s) Relugolix with oestradiol and norethindrone acetate (also
known as norethisterone acetate), alone, or as an add on to
non-hormonal pharmacological treatments
Population(s) People with moderate to severe symptoms associated with
uterine fibroid(s)
Comparators Hormonal treatments, including:
• levonorgestrel-releasing intrauterine system (LNG-
IUS; off-label for some LNG-IUSs)
• combined hormonal contraception (off-label for some
combined hormonal contraceptives)
• cyclical oral progestogens
• gonadotrophin-releasing hormone analogues (off-label
for some gonadotrophin-releasing hormone
analogues)
Outcomes The outcome measures to be considered include:
• change in menstrual blood loss volume
• time to menstrual blood loss response
• pain
• uterine fibroid volume
• haemoglobin levels
• change in bone mineral density
• rates and route of surgery
• impact on fertility and pregnancy and teratogenic
effects
• mortality
• adverse effects of treatment, including but not limited
to vasomotor symptoms, incontinence and pelvic
organ prolapse
• health-related quality of life.
Final scope for the appraisal of relugolix with oestradiol and norethindrone acetate for treating
uterine fibroids
Issue Date: April 2021 Page 2 of 4
© National Institute for Health and Care Excellence 2021. All rights reserved.
Appendix B
Economic analysis The reference case stipulates that the cost effectiveness of
treatments should be expressed in terms of incremental cost
per quality-adjusted life year.
The reference case stipulates that the time horizon for
estimating clinical and cost effectiveness should be
sufficiently long to reflect any differences in costs or
outcomes between the technologies being compared.
Costs will be considered from an NHS and Personal Social
Services perspective.
The availability of any commercial arrangements for the
intervention, comparator and subsequent treatment
technologies will be taken into account.
Other Guidance will only be issued in accordance with the
considerations marketing authorisation. Where the wording of the therapeutic
indication does not include specific treatment combinations,
guidance will be issued only in the context of the evidence
that has underpinned the marketing authorisation granted by
the regulator.
Related NICE Related Technology Appraisals:
recommendations
Fluid-filled thermal balloon and microwave endometrial
and NICE Pathways
ablation techniques for heavy menstrual bleeding (2004).
NICE Technology Appraisal 78. Guidance on the static list.
Related Guidelines:
Heavy menstrual bleeding: assessment and management
(2020). NICE guideline NG88. Review date to be confirmed.
Related Interventional Procedures:
Transcervical ultrasound-guided radiofrequency ablation for
symptomatic uterine fibroids (2021) NICE interventional
procedures guidance 689.
Ultrasound-guided high-intensity transcutaneous focused
ultrasound for symptomatic uterine fibroids (2019). NICE
interventional procedures guidance 657.
Hysteroscopic morcellation of uterine leiomyomas (fibroids)
(2015). NICE interventional procedures guidance 522.
Magnetic resonance image-guided transcutaneous focused
ultrasound for uterine fibroids (2011). NICE interventional
procedures guidance 413.
Uterine artery embolisation for fibroids (2010). NICE
interventional procedures guidance 367.
Magnetic resonance (MR) image-guided percutaneous laser
ablation of uterine fibroids (2003). NICE interventional
procedures guidance 30.
Final scope for the appraisal of relugolix with oestradiol and norethindrone acetate for treating
uterine fibroids
Issue Date: April 2021 Page 3 of 4
© National Institute for Health and Care Excellence 2021. All rights reserved.
Appendix B
Laparoscopic laser myomectomy (2003). NICE interventional
procedures guidance 23.
Interventional Procedures in development:
Laparoscopic morcellation of uterine fibroids. Publication
expected August 2021.
Hysteroscopic removal of uterine fibroids with power
morcellation. Publication expected August 2021.
Related Quality Standards:
Heavy menstrual bleeding (2020). NICE quality standard 47.
Related NICE Pathways:
Heavy menstrual bleeding (2020). NICE pathway
The NHS Long Term Plan, 2019. NHS Long Term Plan
Related National
Policy Department of Health and Social Care, NHS Outcomes
Framework 2016-2017: Domains 2, 4 and 5.
[Link]
framework-2016-to-2017
References
1. NHS. Fibroids. Accessed April 2021 .
2. Mayo Clinic. Uterine fibroids: symptoms and causes. Accessed April 2021.
3. BMJ Best Practice: uterine fibroids. Accessed April 2021.
4. Lumsden M.A.; Fibroids: diagnosis and management; BMJ; 351:h4887; 2015
Final scope for the appraisal of relugolix with oestradiol and norethindrone acetate for treating
uterine fibroids
Issue Date: April 2021 Page 4 of 4
© National Institute for Health and Care Excellence 2021. All rights reserved.