TY - JOUR
T1 - Considerations on implementation of the newest treatment for symptomatic uterine fibroids
T2 - Oral GnRH antagonists
AU - de Lange, Maria E.
AU - Semmler, Annika
AU - Clark, T. Justin
AU - Mol, Ben Willem J.
AU - Bet, Pierre M.
AU - Huirne, Judith A.F.
AU - Hehenkamp, Wouter J.K.
N1 - Funding Information:
T.J.C. declares to have received honoraria from Gedeon Richter, the manufacturer of Ryeqo (an oral GnHR antagonist combination therapy for the treatment of symptomatic fibroid) for a lecture (webinar) in 2022 on the management of fibroids. B.W.J.M. declares to have received an investigator grant (GNT1176437) from NHMRC; to have received consulting fees from ObsEva, Merck KGaA and Guerbet at an hourly rate; to have received travel support from Merck KGaA. J.A.F.H. declares to have received research grants from NOW‐ZonMw/TTW and Samsung on topics not related to the manuscript topic; to have received compensation for expenses made to give an annual course on minimal invasive surgery and for a lecture on imaging on a sponsored session at an international congress. M.D.L, A.S., P.M.B. and W.J.K.H. declare that they have no competing interests.
Publisher Copyright:
© 2023 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.
PY - 2024/2
Y1 - 2024/2
N2 - Novel gonadotrophin releasing hormone (GnRH) antagonist treatments have recently been developed in combination with hormonal add-back therapy, as an oral treatment option for women suffering from uterine fibroids. Registration trials assessing the GnRH antagonist combination preparations with relugolix, elagolix and linzagolix have assessed treatment efficacy for fibroid-related heavy menstrual blood loss in comparison to placebo. Marketing authorization has been granted by several agencies including those in Europe, the United Kingdom and the United States. While the registration trials report a robust effect on the reduction of heavy menstrual blood loss and improvement in quality of life scores, reticence is advised before widespread prescription. In this review, we demonstrate limitations in the trial data, namely a lack of generalizability due to the restricted study population, the lack of transparency in the distribution of disease-level characteristics limiting the predictability of treatment success in the real-world diverse population, and the absence of any comparison to current alternative treatment methods. Importantly, no clinically meaningful volume reductions were found with GnRH antagonist combination preparations, and long-term safety data, particularly concerning modest but stable bone mineral density decline, need further addressing. Symptoms related to uterine fibroids adversely affect many women's quality of life and effective medical treatments are lacking. However, despite the urgent need for conservative treatments, it is vitally important that novel drugs, like combination oral GnRH antagonists, undergo sufficiently rigorous evaluation of safety, effectiveness and cost-effectiveness in a representative population and are compared with alternative treatment methods before introduction into mainstream clinical practice.
AB - Novel gonadotrophin releasing hormone (GnRH) antagonist treatments have recently been developed in combination with hormonal add-back therapy, as an oral treatment option for women suffering from uterine fibroids. Registration trials assessing the GnRH antagonist combination preparations with relugolix, elagolix and linzagolix have assessed treatment efficacy for fibroid-related heavy menstrual blood loss in comparison to placebo. Marketing authorization has been granted by several agencies including those in Europe, the United Kingdom and the United States. While the registration trials report a robust effect on the reduction of heavy menstrual blood loss and improvement in quality of life scores, reticence is advised before widespread prescription. In this review, we demonstrate limitations in the trial data, namely a lack of generalizability due to the restricted study population, the lack of transparency in the distribution of disease-level characteristics limiting the predictability of treatment success in the real-world diverse population, and the absence of any comparison to current alternative treatment methods. Importantly, no clinically meaningful volume reductions were found with GnRH antagonist combination preparations, and long-term safety data, particularly concerning modest but stable bone mineral density decline, need further addressing. Symptoms related to uterine fibroids adversely affect many women's quality of life and effective medical treatments are lacking. However, despite the urgent need for conservative treatments, it is vitally important that novel drugs, like combination oral GnRH antagonists, undergo sufficiently rigorous evaluation of safety, effectiveness and cost-effectiveness in a representative population and are compared with alternative treatment methods before introduction into mainstream clinical practice.
KW - elagolix
KW - fibroids
KW - leiomyoma
KW - linzagolix
KW - oral GnRH antagonist
KW - relugolix
UR - http://www.scopus.com/inward/record.url?scp=85172098091&partnerID=8YFLogxK
U2 - 10.1111/bcp.15897
DO - 10.1111/bcp.15897
M3 - Review Article
C2 - 37653680
AN - SCOPUS:85172098091
SN - 0306-5251
VL - 90
SP - 392
EP - 405
JO - British Journal of Clinical Pharmacology
JF - British Journal of Clinical Pharmacology
IS - 2
ER -