Crnkic Kapetanovic Meliha, Saxne Tore, Truedsson Lennart, Geborek Pierre
Arthritis Res Ther. 2013 Jan 4;15(1):R1. doi: 10.1186/ar4127.
The aim of this study was to explore the persistence of an antibody response 1.5 years after vaccination with 7-valent pneumococcal conjugate vaccine in patients with rheumatoid arthritis (RA) or spondyloarthropathy (SpA) treated with different antirheumatic drugs.
Of 505 patients initially recruited, data on current antirheumatic treatment and blood samples were obtained from 398 (79%) subjects after mean (SD, range) 1.4 (0.5; 1 to 2) years. Antibody levels against pneumococcal serotypes 23F and 6B were analyzed by using enzyme-linked immunosorbent assay (ELISA). Original treatment groups were as follows: (a) RA receiving methotrexate (MTX); (b) RA taking anti-TNF monotherapy; (c) RA taking anti-TNF+MTX; (d) SpA with anti-TNF monotherapy; (e) SpA taking anti-TNF+MTX; and (f) SpA taking NSAID/analgesics. Geometric mean levels (GMLs; 95% CI) and proportion (percentage) of patients with putative protective antibody levels≥1 mg/L for both serotypes, calculated in different treatment groups, were compared with results 4 to 6 weeks after vaccination. Patients remaining on initial treatment were included in the analysis. Possible predictors of persistence of protective antibody response were analysed by using logistic regression analysis.
Of 398 patients participating in the 1.5-year follow up, 302 patients (RA, 163, and SpA, 139) had unchanged medication. Compared with postvaccination levels at 1.5 years, GMLs for each serotype were significantly lower in all groups (P between 0.035 and <0.001; paired-sample t test), as were the proportions of patients with protective antibody levels for both serotypes (P<0.001; χ2 test). Higher prevaccination antibody levels for both serotypes 23F and 6B were associated with better persistence of protective antibodies (P<0.001). Compared with patients with protective antibody levels at 1.5 years, those not having protective antibody levels were older, more often women, had longer disease duration and higher HAQ and DAS, and had a lower proportion of initial responders to both serotypes.
After initial increase, 1.5 years after pneumococcal vaccination with 7-valent conjugate vaccine, postvaccination antibody levels decreased significantly, reaching levels before vaccination in this cohort of patients with established arthritis treated with different antirheumatic drugs. MTX and anti-TNF treatment predicted low persistence of protective immunity among patients with RA. To boost antibody response, early revaccination with conjugate vaccine might be needed in patients receiving potent immunosuppressive remedies.
EudraCT EU 2007-006539-29 and NCT00828997.
本研究旨在探讨类风湿关节炎(RA)或脊柱关节炎(SpA)患者在使用不同抗风湿药物治疗后,接种7价肺炎球菌结合疫苗1.5年后抗体反应的持续性。
在最初招募的505例患者中,平均(标准差,范围)1.4(0.5;1至2)年后从398例(79%)受试者处获得了当前抗风湿治疗的数据和血样。采用酶联免疫吸附测定(ELISA)分析针对肺炎球菌23F和6B血清型的抗体水平。原治疗组如下:(a)接受甲氨蝶呤(MTX)治疗的RA;(b)接受抗TNF单药治疗的RA;(c)接受抗TNF + MTX治疗的RA;(d)接受抗TNF单药治疗的SpA;(e)接受抗TNF + MTX治疗的SpA;(f)接受非甾体抗炎药/镇痛药治疗的SpA。将不同治疗组中计算得出的两种血清型假定保护性抗体水平≥1 mg/L的患者的几何平均水平(GMLs;95%可信区间)和比例(百分比)与接种疫苗后4至6周的结果进行比较。继续接受初始治疗的患者纳入分析。采用逻辑回归分析分析保护性抗体反应持续性的可能预测因素。
在参与1.5年随访的398例患者中,302例患者(RA 163例,SpA 139例)用药未改变。与1.5年后的接种后水平相比,所有组中每种血清型的GMLs均显著降低(P值在0.035至<0.001之间;配对样本t检验),两种血清型保护性抗体水平的患者比例也显著降低(P<0.001;χ2检验)。23F和6B两种血清型接种前抗体水平较高与保护性抗体的更好持续性相关(P<0.001)。与1.5年后有保护性抗体水平的患者相比,没有保护性抗体水平的患者年龄更大,女性更多,病程更长,HAQ和DAS更高,且两种血清型初始应答者的比例更低。
在接种7价结合疫苗的肺炎球菌疫苗1.5年后,接种后抗体水平在最初升高后显著下降,在这组接受不同抗风湿药物治疗的已确诊关节炎患者中降至接种前水平。MTX和抗TNF治疗预示着RA患者中保护性免疫的低持续性。为增强抗体反应,接受强效免疫抑制治疗的患者可能需要早期再次接种结合疫苗。
EudraCT EU 2007 - 006539 - 29和NCT00828997。