Effects of the Live Attenuated Measles-Mumps-Rubella Booster Vaccination on Disease Activity in Patients With Juvenile Idiopathic Arthritis: A Randomized Trial | Pediatrics | JAMA | JAMA Network
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Original Contribution
June 19, 2013

Effects of the Live Attenuated Measles-Mumps-Rubella Booster Vaccination on Disease Activity in Patients With Juvenile Idiopathic Arthritis: A Randomized Trial

Author Affiliations

Author Affiliations: Department of Pediatric Immunology, University Medical Center Utrecht, Wilhelmina Children's Hospital, Utrecht, the Netherlands (Drs Heijstek, Swart, de Vries, and Wulffraat); Department of Pediatric Rheumatology, Erasmus Medical Center Rotterdam, Sophia Children's Hospital, Rotterdam, the Netherlands (Dr Kamphuis); Department of Pediatric Rheumatology, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands (Dr Armbrust); Department of Pediatrics, VU University Medical Center Amsterdam, Amsterdam, the Netherlands (Dr Swart); Department of Internal Medicine, Division of Rheumatology, Maastricht University Medical Center, CAPHRI Research Institute Maastricht, Maastricht, the Netherlands (Dr Gorter); Center for Infectious Disease Control Netherlands, Laboratory for Infectious Diseases and Screening, National Institute of Public Health and the Environment, Bilthoven, the Netherlands (Ms Smits, Mr van Gageldonk, and Dr Berbers).

JAMA. 2013;309(23):2449-2456. doi:10.1001/jama.2013.6768
Abstract

Importance 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.

Objectives To assess whether MMR booster vaccination affects disease activity and to describe MMR booster immunogenicity in patients with JIA.

Design, Setting, and Participants 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.

Intervention 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.

Main Outcomes and Measures 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.

Conclusion and Relevance 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.

Trial Registration clinicaltrials.gov Identifier: NCT00731965

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