Severe Symptoms Of Uterine Fibroids Research Articles

Linzagolix in moderate to severe symptoms of uterine fibroids: a profile of its use

Linzagolix in moderate to severe symptoms of uterine fibroids: a profile of its use

Ryeqo for the treatment of the symptoms of uterine fibroids

Ryeqo is a combined formulation of relugolix, estradiol and norethisterone for the treatment of moderate to severe symptoms of uterine fibroids. This article outlines its efficacy, adverse effects and place in therapy.

Relugolix/Estradiol/Norethisterone (Norethindrone) Acetate: A Review in Symptomatic Uterine Fibroids.

An oral fixed-dose combination of relugolix/estradiol/norethisterone (also known as norethindrone) acetate (Ryeqo®; Myfembree®) has been approved for the management of heavy menstrual bleeding associated with uterine fibroids in the USA and management of moderate to severe symptoms of uterine fibroids in the EU. Relugolix is a gonadotropin releasing hormone (GnRH) receptor antagonist that decreases serum estradiol and progesterone concentrations to postmenopausal levels. The addition of estradiol/norethisterone acetate to relugolix ameliorates relugolix-induced bone loss and hot flush. In the two phase 3 LIBERTY trials, relugolix + estradiol/norethisterone substantially decreased menstrual bleeding and improved a range of other uterine fibroid symptoms in women with uterine fibroids-associated heavy menstrual bleeding. The combination was generally well tolerated, with vasomotor symptoms being the most common adverse reaction. Treatment with this combination for over up to 2 years did not induce a clinically meaningful bone loss in the majority of women. Relugolix/estradiol/norethisterone acetate, with its convenient once-daily administration, is a useful addition to current pharmacological treatment options for premenopausal women with symptomatic uterine fibroids.

Linzagolix: First Approval.

Linzagolix (Yselty®) is an orally administered, selective, non-peptide small molecule gonadotrophin releasing hormone (GnRH) receptor antagonist that is being developed by Kissei Pharmaceutical for the treatment of uterine fibroids and endometriosis in women of reproductive age. Linzagolix binds to and blocks the GnRH receptor in the pituitary gland, modulating the hypothalamic pituitary-gonadal axis and dose-dependently reducing serum luteinising hormone and follicle-stimulating hormone production and serum estradiol levels. In June 2022, linzagolix was approved for the treatment of moderate to severe symptoms of uterine fibroids in adult women of reproductive age in the EU. Linzagolix is under regulatory review the USA for this indication and is in phase 3 clinical development in the treatment of pain associated with endometriosis. This article summarizes the milestones in the development of linzagolix leading to this first approval for the treatment of moderate to severe symptoms of uterine fibroids in adult women of reproductive age.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40265-022-01753-9.

Absence of predictable long-term molecular effect of ulipristal acetate (UPA) on the endometrium.

What are the effects of ulipristal acetate (UPA) on the expression of endometrial proliferation and maturation markers? A total of 45 endometrium-containing blocks of hysterectomy samples from non-menopausal women with a diagnosis of moderate to severe symptoms of uterine fibroids: 14 women operated on at the end of a 3-month course of UPA; four women who had discontinued UPA treatment 1-12 months before surgery; 27 control unexposed samples (14 in the proliferative and 13 in the secretory phase). Immunohistochemical staining of Ki67, vascular endothelial growth factor-receptor 2 (VEGFR2), oestradiol receptor, progesterone receptor, interleukin-15 (IL-15), indoleamin-2,3-dioxygenase (IDO) and C-C motif chemokine ligand-2 (CCL2) markers were analysed in both endometrial compartments and layers. Under UPA, oestradiol receptor and progesterone receptor expression is similar to the proliferative phase in both layers, although with a decrease in cell proliferation. IL-15, IDO and CCL2 expressions are similar to the proliferative phase, suggesting a progesterone-antagonist effect of UPA. VEGFR2 staining suggests a trend to a mixed agonist-antagonist effect. No significant difference is observed in the post-UPA proliferative phase group compared with the control group in both layers of the endometrium. The effect of 3-month UPA treatment is mostly progesterone receptor antagonist-like. After treatment is discontinued, there are no signs of any long-term effects of this molecule on endometrial proliferation and maturation. Therefore, UPA may be administered to women willing to conceive in the short term without consequences for further implantation.

Repeated intermittent ulipristal acetate in the treatment of uterine fibroids: a cost-effectiveness analysis.

There are limited treatment options available for women with moderate to severe symptoms of uterine fibroids (UFs) who wish to avoid surgery. For these women, treatment with standard pharmaceuticals such as contraceptives is often insufficient to relieve symptoms, and patients may require surgery despite their wish to avoid it. Clinical trials demonstrate that ulipristal acetate 5 mg (UPA) is an effective treatment for this patient group, but its cost-effectiveness has not been assessed in this population. A decision-analytic model was developed to simulate a cohort of patients in this population under treatment with UPA followed by surgery as needed compared to treatment with iron and non-steroidal anti-inflammatory drug (NSAID) followed by surgery as needed (best supportive care, BSC). The analysis took the perspective of the National Health Service (NHS) in England, UK, and was based on the published UPA clinical trials. Results were calculated for the long-term costs and quality-adjusted life years (QALYs) for each treatment arm and combined into an incremental cost-effectiveness ratio (ICER) as the primary outcome. The impact of parameter uncertainty on the results was assessed using scenario, deterministic, and probabilistic sensitivity analyses. The results show that treating patients with the UPA strategy, instead of the BSC strategy, results in an additional cost of £1,115 and a gain of 0.087 QALYs, resulting in an ICER of £12,850. Given commonly accepted cost-effectiveness thresholds in England, the use of UPA as a repeated, intermittent treatment for women with moderate to severe symptoms of UF wishing to avoid surgery is likely to be a cost-effective intervention when compared to BSC.

Real-world data of 197 patients treated with ulipristal acetate for uterine fibroids: PREMYA study French population main outcomes

ObjectivesTo characterize and describe treatment with ulipristal acetate (UPA) in a preoperative setting and to evaluate the safety, effectiveness, and Health Related Quality of Life (HRQoL) outcomes in a French population treated according to standard clinical practice. Materials and methodsMulticentre, prospective, non-interventional study (PREMYA) of patients diagnosed with moderate to severe symptoms of uterine fibroids and undergoing a preoperative treatment with UPA 5mg (Esmya®). Patients were followed for a total of 15months (3months UPA treatment and 12months after). Data were collected approximatively every 3months according to centre usual visit schedule. ResultsA total of 206 women were enrolled in France, of whom 197 were found to be eligible for data analysis. Physicians’ assessments of patients’ overall symptomatic changes, as measured on the Clinical Global Impression-Improvement (CGI-I) scale, indicated that 83.7% of patients were improved at end of treatment (month 3). On the patients’ treatment benefit scale (PTBS), 94.7% of patients reported an improvement. These 2 measurements, pain and quality of life, remained improved after treatment cessation and during the entire period of follow-up. Only 58.4% of patients underwent surgery within the timeframe of the study follow-up of which the majority were of a conservative/minimal invasive nature. ConclusionMany patients did not undergo surgery during the planned 12months follow-up period after treatment whereas all patients had an indication of surgery. All measurements of treatment outcome were markedly improved by 3 months of UPA 5mg treatment. Clinical trial numberNCT01635452.

Real world data of 1473 patients treated with ulipristal acetate for uterine fibroids: Premya study results

ObjectivesTo characterize and describe treatment with Ulipristal acetate (UPA) in a pre-operative setting and to evaluate the safety, effectiveness, and Health Related Quality of Life (HRQoL) outcomes in a population treated according to standard clinical practice in the EU. Study designMulti-centre, prospective, non-interventional study (PREMYA) of patients diagnosed with moderate to severe symptoms of uterine fibroids and undergoing a pre-operative treatment with UPA (Esmya®) at 73 clinical practice sites within the EU. Patients were followed during UPA treatment and for 12 months after treatment discontinuation for a total of 15 months follow-up. Data was collected every 3 months in accordance with standard care visits. ResultsA total of 1568 women were enrolled, of whom 1473 were found to be eligible for data analysis. Only 38.8% of patients underwent surgery, of which the majority were of a conservative/minimally invasive nature. Physicians’ assessments of patients’ overall symptomatic change, as measured on the Clinical Global Impression-Improvement (CGI-I) scale, indicated that 60% of patients were much improved or very much improved at 3 months. Pain and quality of life after treatment cessation remain lower than baseline during the entire period of follow-up ConclusionsThe majority of patients do not undergo surgery immediately after treatment cessation. Quality of life and pain are highly improved by Esmya® treatment.

Economic Evaluation of Ulipristal Acetate For The Treatment of Patients With Moderate And Severe Symptoms of Uterine Fibroids Before Surgery In Mexico

Economic Evaluation of Ulipristal Acetate For The Treatment of Patients With Moderate And Severe Symptoms of Uterine Fibroids Before Surgery In Mexico

Ulipristal acetate for use in moderate to severe symptoms of uterine fibroids.

Although it has been known for a long time that uterine fibroids respond to changes in sex steroid concentrations, it is the availability of selective progesterone receptor modulators such as ulipristal acetete that has provided the gynecologist with a novel option for medical management of uterine fibroids. Ulipristal acetate is presently licensed in Europe for use in women with symptomatic fibroids up to 3 months prior to surgery and has demonstrated good clinical efficacy and safety for this indication. Future trials will define the long-term safety of this drug and its role in medical management of uterine fibroids.

PIH33 - Economic Evaluation of Ulipristal Acetate for the Treatment of Patients With Moderate and Severe Symptoms of Uterine Fibroids in Romania

PIH33 Economic Evaluation of Ulipristal Acetate for the Treatment of Patients with Moderate and Severe Symptoms of Uterine Fibroids in Romania Laszlo Lorenzovici1*, Andrea Szekely1, Tamas Agh2, Istvan Vamossy3, Laszlo Kelemen4, Hajnal Finta 5, Zoltan Kalo 6 1. Syreon Research Romania Ltd, Tirgu Mures, Romania; 2. Syreon Research Institute, Budapest, Hungary; 3. Gedeon Richter Plc, Budapest, Hungary; 4. Gedeon Richter Romania SA, Corunca, Romania; 5. University of Medicine and Pharmacy of Tirgu Mures, Tirgu Mures, Romania; 6. Eotvos Lorand University, Budapest, Hungary; * lorenzovici@syreon.ro BACKGROUND Ulipristal acetate 5mg (Esmya®) is a Selective Progesterone Receptor Modulator indicated for the preoperative treatment of moderate to severe symptoms of uterine fibroids in adult women of reproductive age. The aim of this analysis was to assess the cost-effectiveness of ulipristal acetate 5 mg as a 3-month add-on therapy to standard pre-surgical observation and immadiate hysterectomy in Romanian health care settings.

Ulipristal acetate: a novel pharmacological approach for the treatment of uterine fibroids

Uterine fibroids are the most common benign tumors of the female genital tract. The management of symptomatic fibroids has traditionally been surgical; however, alternative pharmacological approaches have been proposed to control symptoms. To date, gonadotropin-releasing hormone analogs are the only available drugs for the preoperative treatment of fibroids. However, the US Food and Drug Administration recently authorized ulipristal acetate (UPA), an oral selective progesterone-receptor modulator, for the same indication. UPA is a new, effective, and well-tolerated option for the preoperative treatment of moderate and severe symptoms of uterine fibroids in women of reproductive age. According to clinical data, UPA shows several advantages: it is faster than leuprolide in reducing the fibroid-associated bleeding, it significantly improves hemoglobin and hematocrit levels in anemic patients, and it grants a significant reduction in the size of fibroids, which lasts for at least 6 months after the end of the treatment. Furthermore, UPA displays a better tolerability profile when compared to leuprolide; in fact, it keeps estradiol levels at mid follicular phase range, thereby reducing the incidence of hot flushes and exerting no impact on bone turnover. On the grounds of this evidence, the administration of 5 mg/day ulipristal acetate for 3 months is suggested for different patient categories and allows for planning a treatment strategy tailored to meet an individual patient’s needs.

The cost-effectiveness of ulipristal acetate tablets in treating patients with moderate to severe symptoms of uterine fibroids

ObjectivesUlipristal acetate is a selective progesterone receptor modulator that has been demonstrated to be an effective 3-month pre-operative treatment for moderate to severe symptoms of uterine fibroids in adult women of reproductive age. The aim of this analysis was to assess the cost-effectiveness of 5mg ulipristal as an add-on therapy to standard pre-surgical observation and treatment in Hungary. Study designA Markov model was developed using a 10-year time horizon. Ulipristal was compared with pre-surgical observation and immediate hysterectomy. The model comprised the following mutually exclusive health states: mild, moderate, severe, or persistent severe excessive bleeding disorder; myomectomy; post-myomectomy with mildly to moderately excessive bleeding disorder; post-myomectomy with severely excessive bleeding disorder; hysterectomy; post-hysterectomy; post-menopause; and death. Transition probabilities and utility values were obtained from clinical trials and the scientific literature. Resource utilisation and unit costs were derived from a consensus panel of clinical experts, National Health Insurance Fund tariffs, and publications. ResultsAdding a 3-month course of ulipristal to pre-operative observation was predicted to achieve an additional 0.021 quality-adjusted life years (QALYs) at an estimated incremental cost of €397, which would result in an incremental cost of €19,200/QALY. When 3 months of ulipristal therapy was compared with immediate hysterectomy, the incremental cost-effectiveness ratio was reduced to €3575/QALY. The results were most sensitive to the utility value of the post-hysterectomy health state but responsive to changes in other model parameters. ConclusionsThe results of this analysis suggest that adding ulipristal treatment to standard pre-surgical therapy represents a good value for money in Hungary. The inclusion of societal benefits may considerably reduce the cost-effectiveness ratio.

Ulipristal acetate – a review of the new therapeutic indications and future prospects

Uterine leiomyomata (ULM) are benign smooth muscle neoplasms that are hormone-dependent. Menorrhagia and anemia are the most common symptoms associated with this disorder. As many as 200000 cases of ULM per year are registered in the USA, and hysterectomy remains the major therapeutic option for treatment. Because gonadal hormones induce or maintain leiomyoma growth, selective progesterone receptor modulators have been evaluated as suitable therapeutic agents. Ulipristal acetate (UPA) is a therapeutic agent used as an emergency contraceptive agent. The therapeutic spectrum of the agent has been expanded by a new indication at the end of 2012. Based on two large-scale international randomized trials (PEARL I and PEARL II), UPA (Esmya tab. 5 mg) received European approval for preoperative treatment of ULM in the spring of 2012. The drug is indicated for treatment of moderate to severe symptoms of uterine fibroids. The duration of the treatment with UPA is limited to no more than 3 months when it is used to reduce the size of the tumor, to stop or reduce bleeding and to increase the red blood count prior to surgery. A disadvantage of the cited studies is that the course of treatment is limited to 3 months. Therefore, more data are needed regarding the benefits and risks of long-term treatment with UPA. The use of UPA in some forms of hypermenorrhoea is discussed as a future therapeutic option but the data are not yet conclusive.

PIH24 Economic Evaluation of Ulipristal Acetate Tablets for the Treatment of Patients with Moderate and Severe Symptoms of Uterine Fibroids

The cost effectiveness analysis compares ulipristal acetate to (1) pre-surgical observation and (2) immediate hysterectomy. A Markov state-transition economic model was developed over a 10 year time horizon. The model comprises mutually exclusive health states: no/mild bleeding disorder, heavy bleeding disorder, persistent heavy bleeding disorder, myomectomy, post-myomectomy with no/mild bleeding disorder, post-myomectomy with heavy bleeding disorder, hysterectomy, posthysterectomy, post-menopausa and death.

Ulipristal acetate: a guide to its use in uterine fibroids

Oral ulipristal acetate (Esmya™), a selective progesterone-receptor modulator, is an effective and well tolerated option for the pre-operative treatment of moderate to severe symptoms of uterine fibroids in adult women of reproductive age. It is associated with rapid control of excessive uterine bleeding and sustained reductions in uterine fibroid volume.