The adjusted odds ratios observed for any vaccine and MS flare-ups requiring hospitalization were similar regardless of sex, with the highest odds observed for the pneumococcal vaccine.
Findings from a large cohort study of more than 35,000 patients with multiple sclerosis (MS) showed no association between the risk of hospitalization for an MS flare-up and vaccination, regardless of age. Considering the number of vaccine subtypes available, investigators concluded that further studies are needed to confirm these data.1
Published in Jama Network Open, the trial featured 106,523 patients with MS included in the System of National Health Databases, a national health claims database in France, with about one-third of this group (n = 35,265; 33.1%) who had a flare-up requiring hospitalization and received at least 1 vaccine. Vaccines observed included the diphtheria, tetanus, poliomyelitis, pertussis, or Haemophilus influenzae (DTPPHi) vaccine, influenza vaccine, and pneumococcal vaccine.
In a case-crossover analysis, the adjusted odds ratios (aOR) any vaccine and MS flare-up requiring hospitalization were 1.00 (95% CI, 0.92-1.09) overall and 1.00 (95% CI, 0.90-1.10) in females and 1.02 (95% CI, 0.88-1.18). The aORs for any vaccine by age group were 0.96 (95% CI, 0.58-1.61) for patients younger than 18 years, 1.19 (95% CI, 0.94-1.51) in those aged 18 to 34 years, 0.94 (95% CI, 0.84-1.04) in those aged 35 to 69 years, and 1.15 (95% CI, 0.95-1.39) in those 70 years old or older.
Led by Lamiae Grimaldi, PhD, PharmD, a professor of clinical pharmacology and pharmacoepidemiology at the Paris Saclay University, the study was considered the most extensive investigation conducted on the risk of the onset of MS flare-ups requiring hospitalization associated with vaccine exposure. The mean follow-up after the date of entry in the MS cohort was 8.8 (SD, 3.1) years and the hospitalization rate for MS flare-ups was 5.78 per 100 person-years of follow-up. This rate was decreased to 3.85 per 100 person-years when only hospitalizations lasting more than 1 day were considered.
Over the 11-year study period, 58,195 (54.6%) patients in the source population received a vaccine throughout any point in time. In a nested case-crossover analysis, cases were defined by vaccine exposure prior to the onset of hospitalization due to an MS flare-up, and flare-up rates were compared with those that occurred prior to vaccine exposure in up to 4 control time windows immediately preceding the at-risk time window for each patient.
Overall, the most frequently prescribed vaccines were DTPPHi (30.3%), influenza (19.2%), and pneumococcus (7.0%), while all others had less than 1% use. At the conclusion of the case-crossover analysis, the observed aORs for MS flare-ups requiring hospitalization based on vaccine were 0.95 (95% CI, 0.82-1.11) for DTPPHi, 0.98 (95% CI, 0.88-1.09) for the influenza vaccine, and 1.20 (95% CI, 0.94-1.55) for the pneumococcal vaccine. In sensitivity analyses, using 30-day and 90-day time windows did not substantially alter the observable risk pattern except for an increase in the aOR for pneumococcal vaccine when a 90-day time window was used (aOR, 1.59; 95% CI, 1.27-1.99).
For context, these findings were consistent with those reported in the literature, which found no increased risk of MS flare-ups following vaccination. The present study by Grimaldi et al had several strengths and limitations, including the fact that the case-crossover design canceled multiple individual confounders since patients are used as their own controls. Although no significant risk was found, the study authors noted that the data cannot completely rule out the existence of a small risk, particularly in the case of the pneuomoccocal vaccine.
While the definition of flare-ups were limited to those that led to hospitalizations and link to a specific MS diagnosis, the investigators noted that it’s possible that some hospitalizations for MS flare-ups may have been missed if they were not coded with a specific MS diagnosis.
"One cannot rule out that some hospitalizations considered in the study were not actual MS flare-ups but possibly other causes or consequences of chronic disease management,” Grimaldi et al wrote. “Yet they would constitute a minority of cases considering the careful exclusion of any hospitalization without a specific MS diagnosis or with only a procedure code.”1