Goenka Luxitaa, George Melvin, Sen Maitrayee
Dept of Clinical Pharmacology, SRM MCH & RC, Kattankulathur, Chennai, Tamil Nadu, 603203, India.
Dept of Clinical Pharmacology, SRM MCH & RC, Kattankulathur, Chennai, Tamil Nadu, 603203, India.
Biomed Pharmacother. 2017 Jun;90:575-585. doi: 10.1016/j.biopha.2017.03.092. Epub 2017 Apr 10.
Endometriosis is a gynaecological disease that is characterised by the presence of endometrium like tissue-epithelium and stroma that develops outside the uterine cavity, which is responsible for pelvic pain and infertility. Even though several medical therapies exist for the treatment of endometriosis, each of the drug class has its own limitations such as cost of treatment, side-effects and its short-term effect on the symptoms of endometriosis. In this review, we have attempted to summarize the current status and challenges of drug development for endometriosis.
A systematic review was done and all the RCTs were selected from the identified hits. We included studies that explored the usage of therapeutic drugs on endometriosis patients from inception till November 2016. The search term used was 'Endometriosis' using PubMed and Clinicaltrials.gov. For the final analysis, 60 articles were analyzed and we identified the newly emerging drug therapies for endometriosis treatment and have briefed their current status and challenges in drug development for endometriosis. The quality of the selected studies was assessed based on the degree of bias.
The current classes of drugs that have shown promising therapeutic results include Gonadotropin- releasing hormone (GnRH) antagonists, aromatase inhibitors (AI), and selective progesterone and estrogen receptor modulators, dopamine receptor-2-agonists and statins. The drugs that failed midway during development include tanezumab, rosiglitazone, infliximab, pentoxifylline, telapristone acetate, asoprisnil and raloxifene.
From the literature review, it appears that the most promising molecules for the treatment of endometriosis in the near future include elagolix, mifepristone, TAK-385, KLH-2109 and ASP1707 and cabergoline. It remains to be seen if these molecules would succeed large phase 3 clinical trials and overcome the regulatory hurdles to become an essential tool in the gynaecologist's armamentarium against endometriosis.
子宫内膜异位症是一种妇科疾病，其特征是子宫腔外出现类似子宫内膜的组织——上皮和间质，这会导致盆腔疼痛和不孕。尽管有多种药物疗法可用于治疗子宫内膜异位症，但每类药物都有其自身的局限性，如治疗成本、副作用以及对子宫内膜异位症症状的短期影响。在本综述中，我们试图总结子宫内膜异位症药物研发的现状和挑战。
进行了系统综述，并从已识别的结果中筛选出所有随机对照试验。我们纳入了从开始到2016年11月期间探索治疗性药物在子宫内膜异位症患者中使用情况的研究。使用PubMed和Clinicaltrials.gov的检索词为“子宫内膜异位症”。最终分析时，对60篇文章进行了分析，我们确定了用于子宫内膜异位症治疗的新兴药物疗法，并简要介绍了它们在子宫内膜异位症药物研发中的现状和挑战。根据偏倚程度评估所选研究的质量。
目前已显示出有前景治疗效果的药物类别包括促性腺激素释放激素（GnRH）拮抗剂、芳香化酶抑制剂（AI）、选择性孕激素和雌激素受体调节剂、多巴胺受体2激动剂和他汀类药物。在研发过程中中途失败的药物包括他尼珠单抗、罗格列酮、英夫利昔单抗、己酮可可碱、醋酸特拉司酮、阿索普瑞诺和雷洛昔芬。
从文献综述来看，在不久的将来，治疗子宫内膜异位症最有前景的分子似乎包括艾拉戈利、米非司酮、TAK - 385、KLH - 2109和ASP1707以及卡麦角林。这些分子是否能在大型3期临床试验中取得成功并克服监管障碍，成为妇科医生对抗子宫内膜异位症的重要手段，还有待观察。
