tak-385 and elagolix

The aim of this NMA is to comprehensively analyze evidence of oral GnRH antagonist in the treatment of moderate-to-severe endometriosis-associated pain.. Literature searching was performed to select eligible studies published prior to April 2022 in PubMed, Cochrane, Embase and Web of Science. Randomized controlled trials involving patients who suffered from moderate-to-severe endometriosis-associated pain and treated with oral nonpeptide GnRH antagonists or placebo were included.. Elagolix 400 mg and ASP1707 15 mg were most efficient in reducing pelvic pain, dysmenorrhea and dyspareunia. Relugolix 40 mg was best in reducing the analgesics use. The rates of any TEAEs and TEAEs-related discontinuation were highest in relugolix 40 mg and elagolix 250 mg, respectively, while rates of hot flush and headache were highest in relugolix 40 mg and elagolix 150 mg. Significantly decreased spinal BMD was observed in elagolix 250 mg.. Oral GnRH antagonists were effective in endometriosis-associated pain in 12w, and most of the efficiency and safety outcomes were expressed in a dose-dependent manner, but linzagolix 75 mg was an exception.

Topics: Endometriosis; Female; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Network Meta-Analysis; Pelvic Pain

To determine the effect relugolix and elagolix have on the production of extracellular matrix (ECM) proteins in human leiomyoma cells.. Laboratory study.. University hospital.. None. January 5, 2022 Cell culture, protein analysis, immunohistochemistry.. Production of GnRHR, COL1A1, FN1, VCAN, p-ERK, & ERK in treated/untreated leiomyoma cells.. 100 nM relugolix resulted in decreased production of COL1A1 at 24 (1.78 0.06-fold; P < .05) and 48 hours (1.92 0.14-fold; P < .05). Elagolix treatment resulted in a decrease in COL1A1 production at 24 but not 48 hours. In 2D and 3D, 100 nM relugolix resulted in decreased production of FN1 at 24 (1.7 ± 0.07-fold; P < .05) and 48 hours (1.8 ± 0.07-fold; P < .05); 100 nM elagolix resulted in decreased production of FN1 at 24 (1.7 ± 0.14-fold; P < .05) and 48 hours (2.0 ± 0.09-fold; P < .05). For cells treated with relugolix 100 nM resulted in decreased VCAN production by 48 hours (0.66 ± 0.07-fold; P < .05). Contrary to our 3D data, 2D elagolix-treated cells demonstrated a decrease in VCAN production that was identified only at 24 hours. For GnRHR, no significant difference between the drugs was seen at 24 hours; at 48 hours production was only significantly decreased for relugolix (P < .05). Comparing both drugs, there was a significant difference in the concentration of p-ERK to ERK at 24 hours (P < .05); there was no difference by 48 hours.. Our findings demonstrated that treatment with either drug can 1) decrease ECM protein production and 2) inhibit the MAPK pathway.

Topics: Cell Culture Techniques, Three Dimensional; Extracellular Matrix; Extracellular Matrix Proteins; Female; Humans; Hydrocarbons, Fluorinated; Leiomyoma; Phenylurea Compounds; Pyrimidines; Pyrimidinones; Uterine Neoplasms