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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Ravelli A, Martini A. Juvenile idiopathic arthritis.  Lancet. 2007;369(9563):767-77817336654PubMedGoogle ScholarCrossref
Beukelman T, Xie F, Chen L,  et al; SABER Collaboration.  Rates of hospitalized bacterial infection associated with juvenile idiopathic arthritis and its treatment.  Arthritis Rheum. 2012;64(8):2773-278022569881PubMedGoogle ScholarCrossref
Salvana EM, Salata RA. Infectious complications associated with monoclonal antibodies and related small molecules.  Clin Microbiol Rev. 2009;22(2):274-29019366915PubMedGoogle ScholarCrossref
British Society for Rheumatology.  Vaccinations in the Immunocompromised Person: Guidelines for the Patient Taking Immunosuppressants, Steroids and the New Biologic Therapies. London, England: British Society for Rheumatology; 2002
Chantler JK, Tingle AJ, Petty RE. Persistent rubella virus infection associated with chronic arthritis in children.  N Engl J Med. 1985;313(18):1117-11234047116PubMedGoogle ScholarCrossref
Ray P, Black S, Shinefield H,  et al; Vaccine Safety Datalink Team.  Risk of chronic arthropathy among women after rubella vaccination.  JAMA. 1997;278(7):551-5569268275PubMedGoogle ScholarCrossref
Borte S, Liebert UG, Borte M, Sack U. Efficacy of measles, mumps and rubella revaccination in children with juvenile idiopathic arthritis treated with methotrexate and etanercept.  Rheumatology (Oxford). 2009;48(2):144-14819074187PubMedGoogle ScholarCrossref
Heijstek MW, Pileggi GC, Zonneveld-Huijssoon E,  et al.  Safety of measles, mumps and rubella vaccination in juvenile idiopathic arthritis.  Ann Rheum Dis. 2007;66(10):1384-138717284544PubMedGoogle ScholarCrossref
Petty RE, Southwood TR, Manners P,  et al; International League of Associations for Rheumatology.  International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001.  J Rheumatol. 2004;31(2):390-39214760812PubMedGoogle Scholar
Heijstek MW, Ott de Bruin LM, Bijl M,  et al; EULAR.  EULAR recommendations for vaccination in paediatric patients with rheumatic diseases.  Ann Rheum Dis. 2011;70(10):1704-171221813547PubMedGoogle ScholarCrossref
Consolaro A, Ruperto N, Bazso A,  et al; Paediatric Rheumatology International Trials Organisation.  Development and validation of a composite disease activity score for juvenile idiopathic arthritis.  Arthritis Rheum. 2009;61(5):658-66619405003PubMedGoogle ScholarCrossref
Giannini EH, Ruperto N, Ravelli A, Lovell DJ, Felson DT, Martini A. Preliminary definition of improvement in juvenile arthritis.  Arthritis Rheum. 1997;40(7):1202-12099214419PubMedGoogle Scholar
Lovell DJ, Ruperto N, Goodman S,  et al; Pediatric Rheumatology Collaborative Study Group; Pediatric Rheumatology International Trials Organisation.  Adalimumab with or without methotrexate in juvenile rheumatoid arthritis.  N Engl J Med. 2008;359(8):810-82018716298PubMedGoogle ScholarCrossref
Centers for Disease Control and Prevention.  Manual for the Surveillance of Vaccine-Preventable Diseases. In: Roush SW, McIntyre L, Baldy LM, eds. 4th ed. Atlanta, GA: Centers for Disease Control and Prevention; 2008
Rümke HC, Visser HK. Vaccinaties op de kinderleeftijd anno 2004, I: effectiviteit en acceptatie van het Rijksvaccinatieprogramma.  Ned Tijdschr Geneeskd. 2004;148(8):356-36315032088PubMedGoogle Scholar
Smits GP, van Gageldonk PG, Schouls LM, van der Klis FR, Berbers GA. Development of a bead-based multiplex immunoassay for simultaneous quantitative detection of IgG serum antibodies against measles, mumps, rubella, and varicella-zoster virus.  Clin Vaccine Immunol. 2012;19(3):396-40022237896PubMedGoogle ScholarCrossref
Thakur A, Pedersen LE, Jungersen G. Immune markers and correlates of protection for vaccine induced immune responses.  Vaccine. 2012;30(33):4907-492022658928PubMedGoogle ScholarCrossref
Andrews N, Pebody RG, Berbers G,  et al.  The European Sero-Epidemiology Network: standardizing the enzyme immunoassay results for measles, mumps and rubella.  Epidemiol Infect. 2000;125(1):127-14111057968PubMedGoogle ScholarCrossref
Consolaro A, Bracciolini G, Ruperto N,  et al; Paediatric Rheumatology International Trials Organization.  Remission, minimal disease activity, and acceptable symptom state in juvenile idiopathic arthritis: defining criteria based on the Juvenile Arthritis Disease Activity Score.  Arthritis Rheum. 2012;64(7):2366-237422231288PubMedGoogle ScholarCrossref
Korematsu S, Miyahara H, Kawano T,  et al.  A relapse of systemic type juvenile idiopathic arthritis after a rubella vaccination in a patient during a long-term remission period.  Vaccine. 2009;27(37):5041-504219576941PubMedGoogle ScholarCrossref
Scheinberg M, Guedes-Barbosa LS, Mangueira C,  et al.  Yellow fever revaccination during infliximab therapy.  Arthritis Care Res (Hoboken). 2010;62(6):896-89820535801PubMedGoogle ScholarCrossref
Plotkin SA. Correlates of protection induced by vaccination.  Clin Vaccine Immunol. 2010;17(7):1055-106520463105PubMedGoogle ScholarCrossref
Pebody RG, Gay NJ, Hesketh LM,  et al.  Immunogenicity of second dose measles-mumps-rubella (MMR) vaccine and implications for serosurveillance.  Vaccine. 2002;20(7-8):1134-114011803074PubMedGoogle ScholarCrossref
Pileggi GS, de Souza CB, Ferriani VP. Safety and immunogenicity of varicella vaccine in patients with juvenile rheumatic diseases receiving methotrexate and corticosteroids.  Arthritis Care Res (Hoboken). 2010;62(7):1034-103920235203PubMedGoogle ScholarCrossref
Frenkel LM, Nielsen K, Garakian A, Jin R, Wolinsky JS, Cherry JD. A search for persistent rubella virus infection in persons with chronic symptoms after rubella and rubella immunization and in patients with juvenile rheumatoid arthritis.  Clin Infect Dis. 1996;22(2):287-2948838185PubMedGoogle ScholarCrossref
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

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