title: Effects of the live attenuated measles-mumps-rubella booster vaccination on disease activity in patients with juvenile idiopathic arthritis: a randomized trial.
abstract: OBJECTIVE
  The immunogenicity and the effects of live attenuated measles-mumps-rubella (MMR) vaccination on disease activity in patients with juvenile idiopathic arthritis (JIA) are matters of concern, especially in patients treated with immunocompromising therapies.
  
  
  OBJECTIVE
  To assess whether MMR booster vaccination affects disease activity and to describe MMR booster immunogenicity in patients with JIA.
  
  
  METHODS
  Randomized, multicenter, open-label clinical equivalence trial including 137 patients with JIA aged 4 to 9 years who were recruited from 5 academic hospitals in The Netherlands between May 2008 and July 2011.
  
  
  METHODS
  Patients were randomly assigned to receive MMR booster vaccination (n=68) or no vaccination (control group; n=69). Among patients taking biologics, these treatments were discontinued at 5 times their half-lives prior to vaccination.
  
  
  METHODS
  Disease activity as measured by the Juvenile Arthritis Disease Activity Score (JADAS-27), ranging from 0 (no activity) to 57 (high activity). Disease activity in the year following randomization was compared between revaccinated patients and controls using a linear mixed model. A difference in JADAS-27 of 2.0 was the equivalence margin. Primary immunogenicity outcomes were seroprotection rates and MMR-specific antibody concentrations at 3 and 12 months.
  
  
  RESULTS
  Of 137 randomized patients, 131 were analyzed in the modified intention-to-treat analysis, including 60 using methotrexate and 15 using biologics. Disease activity during complete follow-up did not differ between 63 revaccinated patients (JADAS-27, 2.8; 95% CI, 2.1-3.5) and 68 controls (JADAS-27, 2.4; 95% CI, 1.7-3.1), with a difference of 0.4 (95% CI, -0.5 to 1.2), within the equivalence margin of 2.0. At 12 months, seroprotection rates were higher in revaccinated patients vs controls (measles, 100% vs 92% [95% CI, 84%-99%]; mumps, 97% [95% CI, 95%-100%] vs 81% [95% CI, 72%-93%]; and rubella, 100% vs 94% [95% CI, 86%-100%], respectively), as were antibody concentrations against measles (1.63 vs 0.78 IU/mL; P = .03), mumps (168 vs 104 RU/mL; P = .03), and rubella (69 vs 45 IU/mL; P = .01). Methotrexate and biologics did not affect humoral responses, but low patient numbers precluded definite conclusions.
  
  
  CONCLUSIONS
  Among children with JIA who had undergone primary immunization, MMR booster vaccination compared with no booster did not result in worse JIA disease activity and was immunogenic. Larger studies are needed to assess MMR effects in patients using biologic agents.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00731965.
authors.affiliation: Department of Pediatric Immunology, University Medical Center Utrecht, Wilhelmina Children's Hospital, Room KC03.063.0, PO Box 85090, 3508 AB, Utrecht, The Netherlands. m.w.heijstek@umcutrecht.nl
authors.forename: Marloes W
authors.initials: MW
authors.lastname: Heijstek
authors.forename: Sylvia
authors.initials: S
authors.lastname: Kamphuis
authors.forename: Wineke
authors.initials: W
authors.lastname: Armbrust
authors.forename: Joost
authors.initials: J
authors.lastname: Swart
authors.forename: Simone
authors.initials: S
authors.lastname: Gorter
authors.forename: Lara D
authors.initials: LD
authors.lastname: de Vries
authors.forename: Gaby P
authors.initials: GP
authors.lastname: Smits
authors.forename: Pieter G
authors.initials: PG
authors.lastname: van Gageldonk
authors.forename: Guy A M
authors.initials: GA
authors.lastname: Berbers
authors.forename: Nico M
authors.initials: NM
authors.lastname: Wulffraat
mesh_terms: D000917:Antibody Formation; D001171:Arthritis, Juvenile / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D005260:Female; D006801:Humans; D007117:Immunization, Secondary / Q000009:adverse effects; D008297:Male; D022542:Measles-Mumps-Rubella Vaccine / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D012720:Severity of Illness Index; D014611:Vaccination; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology
chemical_list: D022542:Measles-Mumps-Rubella Vaccine; D014613:Vaccines, Attenuated