a Department of Clinical Sciences and Community Health , University of Milan, Division of Clinical Rheumatology, ASST Istituto Gaetano Pini - CTO , Milan , Italy.
b Division of Clinical Rheumatology , ASST Istituto Gaetano Pini - CTO , Milan , Italy.
Expert Rev Clin Pharmacol. 2018 Oct;11(10):987-998. doi: 10.1080/17512433.2018.1525293. Epub 2018 Sep 29.
Biological agents have radically changed the prognosis of rheumatic patients. Current evidence demonstrates that tight disease control during pregnancy is mandatory to minimize adverse outcome risk. As the new therapeutic tools are pivotal to maintain appropriate disease activity, it is timely to review available evidence about the safety of biologics and small molecules in pregnancy. Areas covered: A comprehensive literature review has been performed, reporting available data about the passage into breast milk, rate of pregnancy loss and fetal malformations, and long-term complications due to in utero exposure to biological agents and small molecules. Expert commentary: Data about the safety of agents against tumor necrosis factor in pregnancy are reassuring. Even rituximab, tocilizumab, belimumab, ustekinumab, secukinumab, and abatacept have not been associated with an increased rate of fetal abnormalities or adverse pregnancy outcome. Experience with small molecules is too small to draw any conclusion. Even if further data are warranted to define the possible long-term effects of in utero biologic exposure on the infant immune system development, it is reasonable to speculate that in the next future the use of biologics during pregnancy will continue to expand, at least when maternal benefit justifies the potential risk to the fetus.
生物制剂极大地改变了风湿患者的预后。现有证据表明,妊娠期间必须严格控制疾病,以最大限度地降低不良结局风险。由于新的治疗手段对于维持适当的疾病活动至关重要,因此及时回顾生物制剂和小分子药物在妊娠期间的安全性证据非常重要。
进行了全面的文献回顾,报告了有关生物制剂和小分子药物在母乳中转移、流产率和胎儿畸形率,以及因胎儿暴露于生物制剂和小分子药物而导致的长期并发症的现有数据。
关于妊娠期间抗肿瘤坏死因子制剂安全性的数据令人安心。甚至利妥昔单抗、托珠单抗、贝利尤单抗、乌司奴单抗、司库奇尤单抗和阿巴西普也与胎儿异常或不良妊娠结局发生率增加无关。小分子药物的经验还太少,无法得出任何结论。即使需要进一步的数据来定义胎儿在子宫内暴露于生物制剂对婴儿免疫系统发育的可能长期影响,但可以合理推测,在未来,至少在母体获益证明对胎儿存在潜在风险合理的情况下,妊娠期间使用生物制剂的情况将继续扩大。