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TNF 阻滞剂在炎性关节炎患者中对大流行性甲型 H1N1 流感疫苗表现出不同的免疫反应模式。

TNF blockers show distinct patterns of immune response to the pandemic influenza A H1N1 vaccine in inflammatory arthritis patients.

机构信息

Disciplina de Reumatologia, Faculdade de Medicina da Universidade de São Paulo, Av. Dr. Arnaldo, n° 455, 3° andar, sala 3190, Cerqueira César São Paulo, 05403-010, São Paulo, Brazil.

出版信息

Rheumatology (Oxford). 2012 Nov;51(11):2091-8. doi: 10.1093/rheumatology/kes202. Epub 2012 Aug 20.

Abstract

OBJECTIVE

To evaluate the immunogenicity of the anti-influenza A H1N1/2009 vaccine in RA and spondyloarthritis (SpA) patients receiving distinct classes of anti-TNF agents compared with patients receiving DMARDs and healthy controls.

METHODS

One hundred and twenty patients (RA, n = 41; AS, n = 57; PsA, n = 22) on anti-TNF agents (monoclonal, n = 94; soluble receptor, n = 26) were compared with 116 inflammatory arthritis patients under DMARDs and 117 healthy controls. Seroprotection, seroconversion (SC), geometric mean titre, factor increase in geometric mean titre and adverse events were evaluated 21 days after vaccination.

RESULTS

After immunization, SC rates (58.2% vs 74.3%, P = 0.017) were significantly lower in SpA patients receiving anti-TNF therapy, whereas no difference was observed in RA patients receiving this therapy compared with healthy controls (P = 0.067). SpA patients receiving mAbs (infliximab/adalimumab) had a significantly lower SC rate compared with healthy controls (51.6% vs 74.3%, P = 0.002) or those on DMARDs (51.6% vs 74.7%, P = 0.005), whereas no difference was observed for patients on etanercept (86.7% vs 74.3%, P = 0.091). Further analysis of non-seroconverting and seroconverting SpA patients revealed that the former group had a higher mean age (P = 0.003), a higher frequency of anti-TNF (P = 0.031) and mAbs (P = 0.001) and a lower frequency of MTX (P = 0.028). In multivariate logistic regression, only older age (P = 0.015) and mAb treatment (P = 0.023) remained significant factors for non-SC in SpA patients.

CONCLUSION

This study revealed a distinct disease pattern of immune response to the pandemic influenza vaccine in inflammatory arthritis patients receiving anti-TNF agents, illustrated by a reduced immunogenicity solely in SpA patients using mAbs.

TRIAL REGISTRATION

ClinicalTrials.gov, www.clinicaltrials.gov, NCT01151644.

摘要

目的

评估抗流感 A H1N1/2009 疫苗在接受不同类别抗 TNF 药物治疗的类风湿关节炎(RA)和脊柱关节炎(SpA)患者中的免疫原性,与接受 DMARD 治疗的患者和健康对照者进行比较。

方法

120 名接受抗 TNF 药物(单克隆抗体,n = 94;可溶性受体,n = 26)治疗的患者(RA,n = 41;AS,n = 57;PsA,n = 22)与 116 名接受 DMARD 治疗的炎症性关节炎患者和 117 名健康对照者进行比较。在接种疫苗后 21 天评估血清保护率、血清转化率(SC)、几何平均滴度、几何平均滴度的倍数增加和不良事件。

结果

接种疫苗后,SpA 患者(58.2% vs 74.3%,P = 0.017)接受抗 TNF 治疗后的 SC 率明显低于接受该治疗的 RA 患者(与健康对照者相比,P = 0.067)。与健康对照组(51.6% vs 74.3%,P = 0.002)或 DMARD 组(51.6% vs 74.7%,P = 0.005)相比,接受 mAbs(英夫利昔单抗/阿达木单抗)治疗的 SpA 患者的 SC 率明显较低,而接受依那西普治疗的患者之间无差异(86.7% vs 74.3%,P = 0.091)。对未发生血清转化率和发生血清转化率的 SpA 患者进行进一步分析显示,前者的平均年龄更高(P = 0.003),抗 TNF 治疗(P = 0.031)和 mAbs(P = 0.001)的频率更高,而 MTX(P = 0.028)的频率更低。在多变量逻辑回归中,仅年龄较大(P = 0.015)和 mAb 治疗(P = 0.023)是 SpA 患者非 SC 的显著因素。

结论

本研究揭示了接受抗 TNF 药物治疗的炎症性关节炎患者对大流行性流感疫苗的免疫反应存在明显的疾病模式,仅在使用 mAbs 的 SpA 患者中观察到免疫原性降低。

试验注册

ClinicalTrials.gov,www.clinicaltrials.gov,NCT01151644。

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