JAMA：MMR疫苗复种不会使幼年特发性关节炎患儿病情恶化

《美国医学会杂志》2013年6月19日发表的一项研究显示，在接受过初次免疫的幼年特发性关节炎（JIA）患儿中，那些复种麻疹-腮腺炎-风疹增效疫苗（MMR）的患者与未再次接种该疫苗的患者相比，并没有表现出JIA疾病活动恶化的趋势。

文章的背景信息中写道，“幼年特发性关节炎是最常见的儿童期风湿性疾病，每10万人中有16-150人患有这种疾病。JIA患者可能由于其所患疾病的免疫抑制作用或因疾病的治疗而更容易受到感染。JIA患者的感染预防需要有效且安全的疫苗接种，这样的疫苗接种可诱发保护性免疫反应、没有严重不良反应而且不会影响JIA的疾病活动。在世界范围内，各国免疫计划推荐使用的是MMR减毒活疫苗。而对于免疫功能受损的病人，理论上来说，这些病人存在减毒病原体复制扩增的风险，因此减毒活疫苗的安全性仍引发人们的担忧。在JIA患者中进行MMR疫苗接种的安全性尤其受到质疑，因为在既往的小规模无对照研究中曾发现，该疫苗中的风疹组分与关节炎的诱发相关联。”

荷兰Utrecht大学医疗中心Wilhelmina儿童医院的Marloes W. Heijstek博士及其同事开展了一项研究，旨在评估MMR疫苗复种是否会影响JIA患者的疾病活动。在2008年5月至2011年7月间，研究者从荷兰的5家学术医院招募了137名4-9岁的JIA患者。受试者经随机分组后，分别接受MMR疫苗复种（MMR组；n=68）或不再次进行疫苗接种（对照组；n=69）。研究人员通过幼年特发性关节炎疾病活性评分（JADAS-27）对疾病活动性予以衡量，其评分范围为从0（无活动性）至57分（高活动性）。

研究人员发现，在63名MMR组患者（JADAS-27，2.8）及68名对照者（JADAS-27，2.4）之间，在整个随访期间，两组患者的JADAS-27评分均值未见显著差异。随访期间，MMR组（0.44）与对照组（0.34）的平均疾病恶化次数未见明显差异；发生至少1次病情加剧的患者百分比同样未见明显的差异。

在接种之后，所有患者都获得了针对麻疹和风疹的血清学保护。第12个月时，与对照组患者相比，MMR组患者的血清学保护率较高（麻疹：MMR组为100%，对照组为92%；腮腺炎：MMR组为97%，对照组为81%；风疹：MMR组为100%，而对照组为94%），且麻疹、腮腺炎及风疹的相应抗体浓度比对照组高。

文章作者写道，“MMR疫苗接种的安全性之所以受到质疑，是因为对MMR疫苗接种之后疾病恶化的描述。我们的试验没有显示疫苗接种对疾病活性造成某种影响。”“需要进行更大规模的研究来评估MMR在使用生物制剂的病人中的影响。

编者注：荷兰关节炎学会资助了该项研究。

Effects of the live attenuated measles-mumps-rubella booster vaccination on disease activity in patients with juvenile idiopathic arthritis: a randomized trial.
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.