Pregnancy outcomes in the clinical development program of fingolimod in multiple sclerosis

Neurology. 2014 Feb 25;82(8):674-80. doi: 10.1212/WNL.0000000000000137. Epub 2014 Jan 24.

Abstract

Objective: To report outcomes of pregnancies that occurred during the fingolimod clinical development program.

Methods: Pregnancy outcomes from phase II, phase III, and phase IV clinical studies (with optional extensions) were reported by clinical trial investigators. Fingolimod exposure in utero was defined as fingolimod treatment at the time of conception or in the 6 weeks before conception.

Results: As of October 31, 2011, 89 pregnancies were reported in completed or ongoing clinical studies, with 74 in fingolimod treatment arms. Of 66 pregnancies with in utero exposure to fingolimod, there were 28 live births, 9 spontaneous abortions, 24 elective abortions, 4 ongoing pregnancies, and 1 pregnancy with an unknown outcome (patient lost to follow-up). Two infants were born with malformations: 1 with congenital unilateral posteromedial bowing of the tibia and 1 with acrania. Elective abortions were performed for 1 case each of tetralogy of Fallot, spontaneous intrauterine death, and failure of fetal development. There were 5 cases (7.6%; 95% confidence interval 3%-17%) of abnormal fetal development in the 66 pregnancies that had in utero exposure to fingolimod. In all 5 cases, fetal exposure to the drug took place in the first trimester of pregnancy.

Conclusions: The number of patients becoming pregnant during fingolimod therapy remains small and does not permit firm conclusions to be drawn about fetal safety of fingolimod in humans. Given the known risks of teratogenicity in animals and the present data, women of childbearing potential should use effective contraception during fingolimod therapy and for 2 months after discontinuation.

MeSH terms

  • Abnormalities, Drug-Induced*
  • Abortion, Spontaneous / chemically induced
  • Adult
  • Female
  • Fingolimod Hydrochloride
  • Humans
  • Immunosuppressive Agents / adverse effects*
  • Immunosuppressive Agents / therapeutic use
  • Middle Aged
  • Multiple Sclerosis / drug therapy*
  • Pregnancy
  • Pregnancy Complications / chemically induced*
  • Pregnancy Outcome
  • Propylene Glycols / adverse effects*
  • Propylene Glycols / therapeutic use
  • Sphingosine / adverse effects
  • Sphingosine / analogs & derivatives*
  • Sphingosine / therapeutic use

Substances

  • Immunosuppressive Agents
  • Propylene Glycols
  • Fingolimod Hydrochloride
  • Sphingosine