Rebound of multiple sclerosis activity after fingolimod withdrawal due to planning pregnancy: Analysis of predisposing factors

Mult Scler Relat Disord. 2020 Feb:38:101483. doi: 10.1016/j.msard.2019.101483. Epub 2019 Oct 30.

Abstract

Background: Rebound of multiple sclerosis (MS) activity has been described after the withdrawal of high-efficacy drugs, but its impact during pregnancy is less known. We describe a series of cases of rebound syndrome after the cessation of fingolimod due to pregnancy planning.

Methods: The clinical and radiological data of 7 MS patients who discontinued fingolimod therapy between May 2012 and March 2018 to plan a pregnancy was analysed.

Results: Three (42.8%) of the 7 patients experienced a rebound effect, all of whom became pregnant. During pregnancy, the 3 patients had a mean (SD) of 5.3 (1.3) relapses, and 13 of the 15 relapses were treated with intravenous steroids and/or immunoglobulin. These patients experienced a median increase of 3 points in the Expanded Disability Status Scale (range, 2-4), as well as a median increase of 27 new gadolinium-enhancing lesions (range, 9-40) and 38 new T2 lesions in a post-partum MRI (range, 21-70). The 3 pregnancies resulted in the delivery of healthy babies. A strong correlation was found between the lymphocyte count at fingolimod onset and the annual relapse rate in the period without therapy (r= -0.84, p = 0.005). The time to first relapse was shorter in patients who had <300/μl lymphocytes at fingolimod onset (median time 46 vs 426 days, p = 0.010).

Conclusion: Rebound activity after fingolimod suspension represents a severe long-lasting inflammatory syndrome that may affect up to 40% of female MS patient who discontinue therapy due to pregnancy planning. Lymphopenia (<300/μl) in the first 3 months of fingolimod onset may predispose patients to suffer earlier and higher disease activity upon cessation.

Keywords: Fingolimod; Multiple sclerosis; Pregnancy; Rebound; Withdrawal.

MeSH terms

  • Adult
  • Female
  • Fingolimod Hydrochloride / administration & dosage*
  • Humans
  • Immunosuppressive Agents / administration & dosage*
  • Live Birth
  • Lymphocytes*
  • Magnetic Resonance Imaging
  • Multiple Sclerosis* / blood
  • Multiple Sclerosis* / drug therapy
  • Multiple Sclerosis* / pathology
  • Multiple Sclerosis* / physiopathology
  • Pregnancy
  • Pregnancy Complications* / blood
  • Pregnancy Complications* / drug therapy
  • Pregnancy Complications* / pathology
  • Pregnancy Complications* / physiopathology
  • Reproductive Behavior
  • Retrospective Studies
  • Severity of Illness Index
  • Symptom Flare Up*
  • Time Factors

Substances

  • Immunosuppressive Agents
  • Fingolimod Hydrochloride