An alternative to product-specific pregnancy registries? PRIM; PRegnancy outcomes Intensive Monitoring

Reprod Toxicol. 2020 Jun:94:13-21. doi: 10.1016/j.reprotox.2020.03.004. Epub 2020 Mar 10.

Abstract

Patient safety during pregnancy is an important concern. This article presents a method of using an industry safety database to access prospective pregnancy cases. This method, termed here 'PRegnancy outcomes Intensive Monitoring' (PRIM) was developed for fingolimod (Gilenya ™), a treatment option for multiple sclerosis (MS), due to slow enrollment in the company pregnancy registry. The aim of PRIM was to enhance the process of pregnancy data collection and improve data quality, and in particular to enable estimation of the proportion of major congenital malformation and other pregnancy outcomes. To do this, the spontaneous reports of maternal exposure to fingolimod in pregnancy or in the eight weeks immediately before the last menstrual period of patients not enrolled in the pregnancy registry were identified. Follow up checklists were sent at four time points: initial pregnancy report, end of pregnancy, infant attained 3 and 12 months of age. These focused on core data required for derivation of programmed analyses. From 01 Mar 2014 to 28 Feb 2018, a total of 831 prospective maternal exposures with 843 infants were reported, with fetal outcomes reported in 459/843 (54.4 %) of those infants. This enabled the calculation of proportions of pregnancy cases with the main pregnancy outcomes and of fetal cases with malformation. The number of reported pregnancies was significantly higher in PRIM than in the registry, showing that structured use of pharmacovigilance data enables speedier assessment of risks of maternal drug exposure.

Keywords: Intensive monitoring; Maternal exposure; Multiple sclerosis; Pharmacovigilance; Pregnancy outcome; Targeted follow-up.

MeSH terms

  • Abnormalities, Drug-Induced*
  • Adolescent
  • Adult
  • Drug Industry
  • Female
  • Fingolimod Hydrochloride / adverse effects*
  • Fingolimod Hydrochloride / therapeutic use
  • Humans
  • Immunosuppressive Agents / adverse effects*
  • Immunosuppressive Agents / therapeutic use
  • Maternal-Fetal Exchange
  • Middle Aged
  • Multiple Sclerosis / drug therapy*
  • Pharmacovigilance*
  • Pregnancy
  • Pregnancy Outcome
  • Registries
  • Young Adult

Substances

  • Immunosuppressive Agents
  • Fingolimod Hydrochloride