Danish Centre for Expertise in Rheumatology (CeViG), Danish Hospital for Rheumatic Diseases, Sønderborg, Denmark; Department of Regional Health Research, University of Southern Denmark, Odense, Denmark; Thrombosis and Haemostasis, Guy's and St Thomas' NHS Foundation Trust, London, UK.
Danish Centre for Expertise in Rheumatology (CeViG), Danish Hospital for Rheumatic Diseases, Sønderborg, Denmark; Department of Rheumatology, Århus University Hospital, Århus, Denmark.
Lancet Rheumatol. 2024 Aug;6(8):e560-e572. doi: 10.1016/S2665-9913(24)00118-8. Epub 2024 Jun 11.
Rheumatic and musculoskeletal diseases often affect individuals of childbearing age. The incidence and prevalence of rheumatic and musculoskeletal diseases is rising. More pregnancies in patients with rheumatic and musculoskeletal diseases are anticipated and some rheumatic and musculoskeletal diseases are associated with pregnancy complications (eg, miscarriages, fetal deaths, preterm births, and hypertensive disorders in pregnancy). Despite the need to understand the use of drugs to treat rheumatic and musculoskeletal diseases in pregnancy, clinical trials in pregnancy are rare, therapeutics in pregnancy are understudied, and pregnant individuals are routinely excluded as premarketing trial participants. Data on the effectiveness and safety of disease-modifying antirheumatic drugs are most often based on post-marketing observational data. Observational studies assessing the bidirectional relationship between rheumatic and musculoskeletal diseases and pregnancy, as well as interventional studies of treatments during pregnancy, are scarce. Historical reluctance to perform studies in what was deemed an at-risk group persists in pharmaceutical companies, regulatory bodies, and ethics boards. Additionally, patients must be engaged partners, which requires trust that the research respects the needs and interests of the patient and complies with the rules intended to protect the pregnant person and the fetus from harm. In this Series paper, we share challenges we have encountered in conducting prospective cohort studies and interventional trials of postmarketing approved medications, assessing pregnancy specific outcomes in pregnant women with rheumatic and musculoskeletal diseases in the EU, the UK, and the USA. We discuss the changing landscape around trials in pregnancy and present possible solutions to our challenges.
风湿和肌肉骨骼疾病常影响育龄人群。风湿和肌肉骨骼疾病的发病率和患病率正在上升。预计患有风湿和肌肉骨骼疾病的孕妇会增加，一些风湿和肌肉骨骼疾病与妊娠并发症相关（例如，流产、胎儿死亡、早产和妊娠高血压疾病）。尽管需要了解治疗风湿和肌肉骨骼疾病的药物在妊娠期间的使用情况，但妊娠期间的临床试验很少，妊娠期间的治疗方法研究不足，通常将孕妇排除在上市前试验参与者之外。关于疾病修饰抗风湿药物有效性和安全性的数据主要基于上市后观察性数据。评估风湿和肌肉骨骼疾病与妊娠之间双向关系的观察性研究以及妊娠期间治疗的干预性研究都很稀缺。制药公司、监管机构和伦理委员会仍然存在对在被认为存在风险的人群中开展研究的历史抵触情绪。此外，患者必须是参与合作的伙伴，这需要信任研究尊重患者的需求和利益，并遵守旨在保护孕妇和胎儿免受伤害的规则。在本系列论文中，我们分享了在欧盟、英国和美国开展上市后批准药物的前瞻性队列研究和干预性试验、评估风湿和肌肉骨骼疾病孕妇妊娠特异性结局方面遇到的挑战。我们讨论了妊娠试验的变化情况，并提出了我们挑战的可能解决方案。
