Study on ADR Signal Detection of Leuprolide and Goserelin Based on the US FAERS Database
陈乾1,2,3,4,, 陈力1,2,3,, 程艺5
1.四川大学华西第二医院药学部,成都 610041
2.四川大学华西第二医院循证药学中心,成都 610041
3.出生缺陷与相关妇儿疾病教育部重点实验室,成都 610041
4.四川省宜宾市第一人民医院药学部,宜宾 644000
5.重庆医科大学附属儿童医院药学部/儿童发育疾病研究教育部重点实验室,重庆 400014
CHEN Qian1,2,3,4,, CHEN Li1,2,3,, CHENG Yi5
1. Department of Pharmacy, West China Second University Hospital, Sichuan University, Chengdu 610041, China
2. Evidence-Based Pharmacy Center, West China Second University Hospital, Sichuan University, Chengdu 610041, China
3. Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Chengdu 610041, China
4. Department of Pharmacy, the First People's Hospital of Yibin City, Sichuan Province, Yibin 644000, China
5. Department of Pharmacy, Children’s Hospital of Chongqing Medical University, Key Lab of Children Development and Disorders, Ministry of Education, Chongqing 400014, China
Objective To explore and evaluate the post-marketing safety warning signals of leuprolide and goserelin, the representative drugs of GnRHa, and to provide references for the safe use of the two drugs. Methods The adverse drug event (ADE) of leuprolide and goserellin received by the US FAERS from the first quarter of 2009 to the first quarter of 2019 were collected, and the adverse drug reactions (ADR) signal mining was performed by reporting odds ratio (ROR) method and proportional reporting ratio (PRR) method.ADR description terms in the reports were standardized with WHO adverse reaction terminology.Signals of adverse reactions which were screened out were analyzed and compared. Results Total 52 ADR signals of leuprolide and 100 ADR signals of goserellin were obtained, of which 17 signals were overlapped.The most specific ADR signals of leuprolide included hilar lymphadenopathy and mediastinal lymphadenopathy; the most specific ADR signals of goserellin included depilation, insomnia, panic disorder, gastric dilatation, and auditory hypersensitivity. Conclusion In this study, ROR and PRR methods were used to explore and compare the adverse reaction signals of leuprolide and goserellin, and to provide references for clinical rational drug use.
Key words:
Leuprolide
;
Goserelin
;
ADR signals
;
Measures of disproportionality
;
Reporting Odds Ratio (ROR)
;
Proportional Reporting Ratio (PRR)
LIN MH,WU SY,HWU YM,et al.Dual trigger with gonadotropin releasing hormone agonist and human chorionic gonadotropin significantly improves live birth rate for women with diminished ovarian reserve[J].Reprod Biol Endocrinol,2019,17(1):7.
BACKGROUND: Diminished ovarian reserve (DOR) remains one of the greatest obstacles affecting the chance of a successful live birth after fertility treatment. The present study was set to investigate whether using a
YANG XH,ZHANG XF,LINB,et al.Combined thera-peutic effects of HIFU,GnRH-a and LNG-IUS for the treatment of severe adenomyosis[J].Int J Hyperthermia,2019,36(1):485-491.
ZANG YQ,DONG MT,ZHANGK,et al.Hormonal the-rapy in uterine sarcomas[J].Cancer Med,2019,8(4):1339-1349.
Uterine sarcomas (USs) are a group of rare but aggressive uterine malignancies, accounting for only 1% of the malignant tumors of female reproductive organs. Due to the high rate of recurrence and metastasis, the prognosis of USs is poor. Given the high mortality rate and limited clinical benefit of surgery and adjuvant chemoradiotherapy, hormonal therapy has shown good prospects in recent years. Hormonal agents include progestins, aromatase inhibitors (AIs), and gonadotropin-releasing hormone analogue (GnRH-a). According to the literature, hormonal therapy has been confirmed effective for recurrent, metastatic or unresectable low-grade endometrial stromal sarcoma (LGESS) and hormone receptor positive (ER+/PR+) uterine leiomyosarcoma (uLMS) with favorable tolerance and compliance. Besides, hormonal therapy can also be used in patients with early-staged disease who desire to preserve fertility. However, due to the rarity of USs, the rationale of hormonal therapy is generally extrapolated from data of hormone-sensitive breast cancer, and present studies of hormonal therapy in USs were almost limited to case reports and small-sized retrospective studies. Therefore, further systematic researches and standardized clinical trials are needed to establish the optimal hormonal therapy regimen of USs. Herein, we reviewed the existing studies related to the hormonal therapy in USs in order to provide reference for clinical management in specific settings.
VAN PUIJENBROEK EP,BATEA,LEUFKENS HG,et al.A comparison of measures of disproportionality for signal detection in spontaneous reporting systems for adverse drug reaction[J].Pharmacoepidemiol Drug Saf,2002,11(1):3-10.
PURPOSE: A continuous systematic review of all combinations of drugs and suspected adverse reactions (ADRs) reported to a spontaneous reporting system, is necessary to optimize signal detection. To focus attention of human reviewers, quantitative procedures can be used to sift data in different ways. In various centres, different measures are used to quantify the extent to which an ADR is reported disproportionally to a certain drug compared to the generality of the database. The objective of this study is to examine the level of concordance of the various estimates to the measure used by the WHO Collaborating Centre for International ADR monitoring, the information component (IC), when applied to the dataset of the Netherlands Pharmacovigilance Foundation Lareb. METHODS: The Reporting Odds Ratio--1.96 standard errors (SE), proportional reporting ratio--1.96 SE, Yule's Q--1.96 SE, the Poisson probability and Chi-square test of all 17,330 combinations were compared with the IC minus 2 standard deviations. Additionally, the concordance of the various tests, in respect to the number of reports per combination, was examined. RESULTS: In general, sensitivity was high in respect to the reference measure when a combination of point- and precision estimate was used. The concordance increased dramatically when the number of reports per combination increased. CONCLUSION: This study shows that the different measures used are broadly comparable when four or more cases per combination have been collected.
WU DB,HUM,HONGL,et al.Clinical efficacy of add-back therapy in treatment of endometriosis:a meta-analysis[J].Arch Gynecol Obstet,2014,290(3):513-523.
A meta-analysis was conducted to determine the effectiveness of using gonadotropin-releasing hormone analogues (GnRH-a), both with and without hormonal add-back therapy, for the management of endometriosis. Cochrane library, Ovid (Embase) and Pubmed databases were searched between the years 1998 and 2013 for published, prospective, randomised controlled trials (RCT) that assessed the effectiveness of "add-back" therapy for EMs treatment. The meta-analysis was performed using RevMan V5.0. The main outcome measures were as follows: lumbar spine bone mineral density (BMD) immediately after treatment and after 6 months of follow-up; femoral neck BMD; serum estradiol levels; changes in the Kupperman index score; the pelvic pain score, including dysmenorrhoea and dyspareunia; and pelvic tenderness. A total of 13 RCT, including 945 participants, were identified. The evidence suggested that "add-back" therapy was more effective for symptom relief than GnRH-a alone. BMD was significantly different when comparing "add-back" therapy to GnRH-a alone, both immediately after treatment and at 6 months. The "add-back" therapy increased serum oestrogen and did not reduce the efficacy of GnRH-a for treating dysmenorrhoea and dyspareunia. A variety of add-back regimens had a same effect for the treatment of endometriosis. "Add-back" therapy, based on the GnRH-a dose, does not reduce the efficacy of using GNRH-a for the management of endometriosis. "Add-back" therapy reduced the occurrence of side effects that can occur with GnRH-a therapy alone, such as osteoporosis and menopausal syndrome. There were no statistically significant differences when comparing the effectiveness of a variety of "add-back" regimens to each other.
SEO JW,LEE DY,KIM SE,et al.Comparison of long-term use of combined oral contraceptive after gonadotropin-releasing hormone agonist plus add-back therapy versus dienogest to prevent recurrence of ovarian endometrioma after surgery[J].Eur J Obstet Gynecol Reprod Biol,2019,236:53-57.
OBJECTIVE: The aim of this study was to compare long-term use of combined oral contraceptive (COC) after gonadotropin-releasing hormone (GnRH) agonist plus add-back therapy with dienogest (DNG) treatment as medical treatments after surgery for ovarian endometrioma. METHODS: This prospective cohort study analyzed 52 reproductive-aged women who underwent surgery for ovarian endometrioma and received postoperative medical treatment with either COC after GnRH agonist (n = 20) or DNG (n = 32) for 24 months. Changes in quality-of-life (QOL) and bone mineral density (BMD) were compared according to treatment. In addition, recurrence of pain and lesions were compared. RESULTS: Baseline characteristics did not differ in demographic profiles and factors associated with endometriosis or QOL. During 24 months of treatment, no differences in any component of QOL were found between the two groups. BMD at the lumbar spine significantly decreased after the first 6 months of treatment in both COC after GnRH agonist (-3.5%) and DNG (-2.3%) groups, but the groups did not differ statistically. After 6 months, further decrease in BMD was not observed until 24 months in both groups. In addition, no cases of pain or endometrioma recurrence were found. CONCLUSION: Our results suggest that long-term use of COC after GnRH agonist plus add-back therapy is comparable to dienogest as a long-term postoperative medical treatment for endometriosis.
AKHKUBEKOVA NK,KAYSINOVA AS,FEDOROV AA,et al.The role of the combined balneotherapeutic treatment as the “add-back therapy” against the background of the anti-hormonal effects of the agonists of gonadotropin-releasing hormone in the women suffering from endometriosis genitalis externa[J].Vopr Kurortol Fizioter Lech Fiz Kult,2018,95(5):31-39.
BACKGROUND: The use of agonists of gonadotropin-releasing hormone (GnRH) for the rehabilitation treatment of the patients presenting with endometriosis genitalis externa is known to significantly enhance the risk of development of hypoestrogenism. The so-called 'add-back-therapy' is carried out as a preventive measure to eliminate hypoestrogenism caused by the intake of GnRH agonists without detriment to the effectiveness of anti-hormonal therapy. AIM: The objective of the present study was to estimate the effectiveness of the new method ('add-back hormone replacement therapy') in comparison with anti-hormonal therapy with the use of GRH agonists at the stage of the early postoperative medical rehabilitation based on the drinking of mineral waters (MW) and radon therapy (RT) in the patients who had undergone the laparoscopic interventions for the treatment of endometrioid heterotopies of the ovaries (1-3 months post-operatively). MATERIAL AND METHODS: To evaluate the effectiveness of the spa and health resort-based rehabilitation measures, the long-term effects of GnRH agonists have been studied in 2 groups of the patients formed by the of simple randomization method. The main group (MG) was comprised of 45 women received medical rehabilitation under conditions of a spa and health resort setting with the application of medium-salt water from the Pyatigorsk spring and radon therapy in the combination with triptorelin. The group of comparison (CG) was composed of 44 women given the treatment with the use of triptorelin under the out-patient conditions. The assessment of the results of the study included: the estimation of the intensity of pelvic pain syndrome, indicators of the hormonal status and the quality of life (QL), ultrasonic examination of the pelvic organs, and the occurrence of adverse effects of triptorelin. The duration of the study was 3 years (2014-2016). RESULTS: The analysis of the long-term results of the rehabilitative treatment has demonstrated that the rehabilitation activities under the spa and health resort conditions within 1-3 months after the surgical intervention including the application of MW and RT in the combination with an agonist of gonadotropin-releasing hormone (triptorelin) greatly contributed to the stability of the results of the treatment: specifically, only 2.5% of the patients suffered the recurrence of cystic ovarian endometriosis whereas 24.5% (p<0.001) reported the restoration of the reproductive function. The patients comprising the control group experienced the recurrence of the pathologic process in 7.5% of the cases and the restoration of the reproductive function in 15.8% of the cases (p<0.001). Simultaneously, the quality of life in the patients in the main group improved 3.4 times on the average in comparison with the initial level (p<0.001). The 2.2-fold improvement of the quality of life was documented in the control patients (p<0.001). At the same time, the frequency of adverse reactions to the treatment with triptorelin in the control patients was higher than in the main group including pain in the epigastric area, headache, irritability, hyperhidrosis, and instability of arterial blood pressure (ABP) that significantly deteriorated the life quality in these women. CONCLUSION: The comparative analysis of the results of the follow-up observations has demonstrated that the application of drinking mineral water and radon therapy for the treatment of the women suffering from endometriosis genitalis externa can be recommended as 'add-back therapy' against the background of anti-hormonal effects of agonists of gonadotropin-releasing hormone.
OSUGAY,TORNG PL,JENG CJ.Clinical studies investi-gating the use of leuprorelin in Asian women with endometriosis:a review[J].J Obstet Gynaecol,2019,39(3):291-296.
We aimed to examine how leuprorelin has been studied for the treatment of women with endometriosis in Asia. We conducted a literature search of PubMed, the Cochrane Library and ClinicalTrials.gov. This review includes randomised trials of women with endometriosis treated with leuprorelin in Asia. Phase I-IV clinical trials published between January 1 2000 and December 31 2016 and written in English were included. Four studies were identified, showing that leuprorelin significantly improves pain and quality of life. The oestrone and oestradiol levels are decreased by leuprorelin but can be increased using an 'add-back' therapy with conjugated equine oestrogen and methoxyprogesterone. Menopause is more common in women treated with leuprorelin. The bone mineral density is reduced in women treated with leuprorelin. There are limited studies investigating the use of leuprorelin for the treatment of endometriosis in Asian populations. However, the research that has been conducted supports the use of leuprorelin in an Asian population.
GEOFFRONS,COHENJ,SAUVANM,et al.Endometriosis medical treatment:hormonal treatment for the management of pain and endometriotic lesions recurrence.CNGOF-HAS Endometriosis Guidelines[J].Gynecol Obstet Fertil Senol,2018,46(3):231-247.
The available literature, from 2006 to 2017, on hormonal treatment has been analysed as a contribution to the HAS-CNGOF task force for the treatment of endometriosis. Available data are heterogeneous and the general level of evidence is moderate. Hormonal treatment is usually offered as the primary option to women suffering from endometriosis. It cannot be used in women willing to conceive. In women who have not been operated, the first line of hormonal treatment includes combined oral contraceptives (COC) and the levonorgestrel-releasing intra uterine system (52mg LNG-IUS). As a second line, desogestrel progestin only pills, etonogestrel implants, GnRH analogs (GnRHa) with add back therapy and dienogest can be offered. Add back therapy should include estrogens to prevent bone loss and improve quality of life, it can be introduced before the third month of treatment to prevent side effects. The literature does not support preoperative hormonal treatment for the sole purpose of reducing complications or recurrence, or facilitating surgical procedures. After surgical treatment, hormonal treatment is recommended to prevent pain recurrence and improve quality of life. COCs or LNG IUS are recommended as a first line. To prevent recurrence of endometriomas COC is advised and maintained as long as tolerance is good in the absence of pregnancy plans. In case of dysmenorrhea, postoperative COC should be used in a continuous scheme. GnRHa are not recommended in the sole purpose of reducing endometrioma recurrence risk.
Dual trigger with gonadotropin releasing hormone agonist and human chorionic gonadotropin significantly improves live birth rate for women with diminished ovarian reserve
Comparison of long-term use of combined oral contraceptive after gonadotropin-releasing hormone agonist plus add-back therapy versus dienogest to prevent recurrence of ovarian endometrioma after surgery
The role of the combined balneotherapeutic treatment as the “add-back therapy” against the background of the anti-hormonal effects of the agonists of gonadotropin-releasing hormone in the women suffering from endometriosis genitalis externa
, 陈力
