林扎戈利克治疗子宫肌瘤患者的疼痛减轻：PRIMROSE 1和2期3试验的二次中介分析
Pain Reduction in Linzagolix-Treated Patients With Uterine Fibroids: A Secondary Mediation Analysis of the PRIMROSE 1 and 2 Phase 3 Trials.
作者信息
Becker Sven, Dolmans Marie-Madeleine, Herrera Francisco Carmona, Petraglia Felice, Renner Stefan P, Ionescu-Ittu Raluca, St-Pierre Julien, Boolell Mitra, Bestel Elke, Hori Satoshi, Donnez Jacques
机构信息
Department of Gynecology and Obstetrics, University Hospital Frankfurt, Frankfurt, Germany.
Gynecology Research Laboratory, Institut de Recherche Expérimentale et Clinique, Department of Gynecology, Université Catholique de Louvain, Brussels, Belgium.
出版信息
BJOG. 2025 Aug;132(9):1297-1306. doi: 10.1111/1471-0528.18190. Epub 2025 May 6.
OBJECTIVE
Among women with uterine fibroids (UFs), we assess the extent to which the linzagolix effect on pain alleviation is explained by its effect on reducing heavy menstrual bleeding (HMB) and fibroid volume (FV).
DESIGN
Post hoc analysis on the pooled data from two randomised double-blind placebo-controlled phase 3 trials.
SETTING
94 sites in the US (PRIMROSE 1 trial) and 95 sites in Europe/US (PRIMROSE 2 trial).
POPULATION
Women aged ≥ 18 years with ultrasound-confirmed UFs and HMB (n = 1012).
METHODS
Participants were randomised to linzagolix (100 mg and 200 mg, with and without hormonal add-back therapy) versus placebo. A post hoc mediation analysis was conducted on the pooled PRIMROSE 1 and PRIMROSE 2 data. The effect of linzagolix versus placebo on pain reduction was divided into three components (effect explained by HMB reduction associated with linzagolix, FV reduction associated with linzagolix, and remaining [not yet explained] treatment effect), with proportions of each component reported.
MAIN OUTCOME MEASURES
The mediation analysis outcome was clinically significant pain reduction, defined as a change of ≥ 2 pain categories from baseline to Week 24 using the Numeric Rating Scale (pain categories: no pain (0), and mild (1-3), moderate (4-6), severe pain (7-10)).
RESULTS
In the mediation analysis, 28%-51% (depending on treatment arm) of linzagolix effect on pain reduction was explained by its effect on HMB reduction, while 2%-8% was explained by its effect on FV reduction. The residual proportion ranged between 44% and 67%, depending on treatment arm, and was statistically significant only in the linzagolix 200 mg without add-back therapy arm (p = 0.002).
CONCLUSIONS
This analysis showed that reductions in pain were significantly mediated by reductions in HMB (all doses) and FV (200 mg alone) in linzagolix-treated women with UFs. Further research is needed to identify additional mediating factors.
TRIAL REGISTRATION
ClinicalTrials.gov: NCT03070899 and NCT03070951.
目的
在患有子宫肌瘤（UFs）的女性中，我们评估林扎戈利克对减轻疼痛的效果在多大程度上可由其对减少月经过多（HMB）和子宫肌瘤体积（FV）的作用来解释。
设计
对两项随机双盲安慰剂对照3期试验的汇总数据进行事后分析。
地点
美国的94个研究点（PRIMROSE 1试验）和欧洲/美国的95个研究点（PRIMROSE 2试验）。
研究对象
年龄≥18岁、经超声确诊患有UFs和HMB的女性（n = 1012）。
方法
参与者被随机分配至林扎戈利克组（100 mg和200 mg，有或无激素补充治疗）与安慰剂组。对PRIMROSE 1和PRIMROSE 2的汇总数据进行事后中介分析。将林扎戈利克与安慰剂相比对减轻疼痛的效果分为三个部分（由林扎戈利克相关的HMB减少所解释的效果、由林扎戈利克相关的FV减少所解释的效果以及剩余的[尚未解释的]治疗效果），并报告每个部分的比例。
主要观察指标
中介分析的结果为临床上显著减轻疼痛，定义为使用数字评定量表从基线到第24周疼痛类别改变≥2级（疼痛类别：无疼痛（0）、轻度（1 - 3）、中度（4 - 6）、重度疼痛（7 - 10））。
结果
在中介分析中，林扎戈利克对减轻疼痛的效果有28% - 51%（取决于治疗组）可由其对HMB减少的作用来解释，而有2% - 8%可由其对FV减少的作用来解释。剩余比例在44%至67%之间，取决于治疗组，且仅在林扎戈利克200 mg无补充治疗组有统计学意义（p = 0.002）。
结论
该分析表明，在接受林扎戈利克治疗的患有UFs的女性中，疼痛减轻显著由HMB减少（所有剂量）和FV减少（仅200 mg）介导。需要进一步研究以确定其他中介因素。
试验注册
ClinicalTrials.gov：NCT03070899和NCT03070951。
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