Department of Rheumatology, Clinical Research Center for Rheumatic Disease, NHO Kumamoto Saishunsou National Hospital, Kohshi, Kumamoto, Japan.
Ann Rheum Dis. 2013 Aug;72(8):1362-6. doi: 10.1136/annrheumdis-2012-202658. Epub 2013 Jan 23.
We assessed the impact of tocilizumab (TCZ), a humanised monoclonal anti-interleukin-6 receptor antibody, on antibody response following administration of the 23-valent pneumococcal polysaccharide vaccine (PPV23).
A total of 190 patients with rheumatoid arthritis (RA) received PPV23. Patients were classified into TCZ (n=50), TCZ + methotrexate (MTX) (n=54), MTX (n=62) and RA control (n=24) groups. We measured serotype-specific IgG concentrations of pneumococcal serotypes 6B and 23F using ELISA and functional antibody activity using a multiplexed opsonophagocytic killing assay, reported as the opsonisation indices (OIs), before and 4-6 weeks after vaccination. Positive antibody response was defined as a 2-fold or more increase in the IgG concentration or as a ≥10-fold or more increase in the OI.
IgG concentrations and OIs were significantly increased in all treatment groups in response to vaccination. The TCZ group antibody response rates were comparable with those of the RA control group for each serotype. MTX had a negative impact on vaccine efficacy. Multivariate logistic analysis confirmed that TCZ is not associated with an inadequate antibody response to either serotype. No severe adverse effect was observed in any treatment group.
TCZ does not impair PPV23 immunogenicity in RA patients, whereas antibody responses may be reduced when TCZ is used as a combination therapy with MTX.
评估人源化抗白细胞介素-6 受体单克隆抗体托珠单抗(TCZ)对 23 价肺炎球菌多糖疫苗(PPV23)接种后抗体应答的影响。
共 190 例类风湿关节炎(RA)患者接受了 PPV23 接种。将患者分为 TCZ(n=50)、TCZ+甲氨蝶呤(MTX)(n=54)、MTX(n=62)和 RA 对照组(n=24)。我们使用 ELISA 法检测肺炎球菌血清型 6B 和 23F 的血清型特异性 IgG 浓度,并用多重调理吞噬杀伤测定法检测功能性抗体活性,报告为调理指数(OI),在接种前和接种后 4-6 周进行检测。阳性抗体应答定义为 IgG 浓度增加 2 倍或以上,或 OI 增加 10 倍或以上。
所有治疗组在接种后 IgG 浓度和 OI 均显著增加。TCZ 组对每种血清型的抗体应答率与 RA 对照组相当。MTX 对疫苗疗效有负面影响。多变量逻辑分析证实,TCZ 与任一血清型的抗体应答不足无关。任何治疗组均未观察到严重不良事件。
TCZ 不会损害 RA 患者的 PPV23 免疫原性,而当 TCZ 与 MTX 联合治疗时,抗体应答可能会降低。