Vaccinations and the risk of relapse in multiple sclerosis. Vaccines in Multiple Sclerosis Study Group

N Engl J Med. 2001 Feb 1;344(5):319-26. doi: 10.1056/NEJM200102013440501.


Background: There has been some concern that vaccination may precipitate the onset of multiple sclerosis or lead to relapses. Since the recent hepatitis B vaccination program in France, there have been new reports of an increased risk of active multiple sclerosis after vaccination.

Methods: We conducted a case-crossover study to assess whether vaccinations increase the risk of relapse in multiple sclerosis. The subjects were patients included in the European Database for Multiple Sclerosis who had a relapse between 1993 and 1997. The index relapse was the first relapse confirmed by a visit to a neurologist and preceded by a relapse-free period of at least 12 months. Information on vaccinations was obtained in a standardized telephone interview and confirmed by means of medical records. Exposure to vaccination in the two-month risk period immediately preceding the relapse was compared with that in the four previous two-month control periods for the calculation of relative risks, which were estimated with the use of conditional logistic regression.

Results: Of 643 patients with relapses of multiple sclerosis, 15 percent reported having been vaccinated during the preceding 12 months. The reports of 94 percent of these vaccinations were confirmed. Of all the patients, 2.3 percent had been vaccinated during the preceding two-month risk period as compared with 2.8 to 4.0 percent who were vaccinated during one or more of the four control periods. The relative risk of relapse associated with exposure to any vaccination during the previous two months was 0.71 (95 percent confidence interval, 0.40 to 1.26). There was no increase in the specific risk of relapse associated with tetanus, hepatitis B, or influenza vaccination (range of relative risks, 0.22 to 1.08). Analyses based on risk periods of one and three months yielded similar results.

Conclusions: Vaccination does not appear to increase the short-term risk of relapse in multiple sclerosis.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Case-Control Studies
  • Female
  • Humans
  • Influenza Vaccines / adverse effects
  • Logistic Models
  • Male
  • Multiple Sclerosis / etiology*
  • Recurrence
  • Risk
  • Tetanus Toxoid / adverse effects
  • Vaccination / adverse effects*
  • Viral Hepatitis Vaccines / adverse effects


  • Influenza Vaccines
  • Tetanus Toxoid
  • Viral Hepatitis Vaccines