类风湿关节炎患者应用灭活 SARS-CoV-2 疫苗后，联合治疗与单药治疗对免疫原性的影响不同。
Distinct impact of DMARD combination and monotherapy in immunogenicity of an inactivated SARS-CoV-2 vaccine in rheumatoid arthritis.
机构信息
Rheumatology Division, Hospital das Clinicas da Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil.
Pediatric Rheumatology Unit, Instituto da Criança, Hospital das Clinicas da Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil.
出版信息
Ann Rheum Dis. 2022 May;81(5):710-719. doi: 10.1136/annrheumdis-2021-221735. Epub 2022 Feb 8.
OBJECTIVES
To evaluate the distinct impact of disease modifying antirheumatic drugs (DMARD) combination and monotherapy in immune response to an inactivated SARS-CoV-2 vaccine in patients with rheumatoid arthritis (RA).
METHODS
This phase 4 prospective study analysed seroconversion (SC) of anti-SARS-CoV-2 immunoglobulin G (IgG) and neutralising antibodies (NAb) induced by the inactivated vaccine (CoronaVac) in patients with RA in comparison to controls (CG). Disease activity and treatment were also assessed. Only participants with baseline negative IgG/NAb were included.
RESULTS
Patients with RA (N=260) and CG (N=104) had comparable median ages (59 years (50-65 years) vs 58 years (49.8-64 years), p=0.483). Patients with RA had moderate but lower SC (61.8% vs 94.2%, p<0.001) and NAb positivity (45% vs 78.6%, p<0.001) in comparison to CG after full vaccination. Baseline disease activity did not influence immunogenicity (p>0.05). After multivariate analyses, factors independently related to reduced SC were: older age (OR=0.79 (0.70-0.89) for each 5-year interval, p<0.001), methotrexate (OR=0.54 (0.29-0.98), p=0.044), abatacept (OR=0.37 (0.19-0.73), p=0.004) and number of DMARD (OR=0.55 (0.33-0.90), p=0.018). Regarding NAb, age (OR=0.87 (0.78-0.96) for each 5-year interval, p=0.007) and prednisone >7.5 mg/day (OR=0.38 (0.19-0.74), p=0.004) were negatively related to the presence of NAb. Further comparison of SC/NAb positivity among RA treatment subgroups and CG revealed that methotrexate/tofacitinib/abatacept/tocilizumab use, in monotherapy or in combination, resulted in lower responses (p<0.05), while tumour necrosis factor inhibitor and other conventional synthetic DMARD interfered solely when combined with other therapies.
CONCLUSIONS
Patients with RA under DMARD have a moderate immunogenicity to CoronaVac. We identified that nearly all DMARD combinations have a deleterious effect in immunogenicity, whereas a more restricted number of drugs (methotrexate/tofacitinib/abatacept/tocilizumab) also hampered this response as monotherapy. These findings reinforce the need of a broader approach, not limited to specific drugs, to improve vaccine response for this population.
TRIAL REGISTRATION DETAILS
NCT04754698.
目的
评估疾病修饰抗风湿药物（DMARD）联合治疗与单药治疗对类风湿关节炎（RA）患者对灭活 SARS-CoV-2 疫苗免疫应答的影响。
方法
本 4 期前瞻性研究比较了 RA 患者（N=260）和对照组（CG，N=104）对灭活疫苗（科兴疫苗）诱导的抗 SARS-CoV-2 免疫球蛋白 G（IgG）和中和抗体（NAb）的血清转化率（SC）。还评估了疾病活动度和治疗情况。仅纳入基线 IgG/NAb 阴性的患者。
结果
RA 患者和 CG 的中位年龄相当（59 岁（50-65 岁）vs 58 岁（49.8-64 岁），p=0.483）。与 CG 相比，RA 患者在完全接种疫苗后 IgG 阳性率（61.8% vs 94.2%，p<0.001）和 NAb 阳性率（45% vs 78.6%，p<0.001）较低。基线疾病活动度与免疫原性无关（p>0.05）。多变量分析后，与 SC 降低相关的因素为：年龄较大（每 5 岁间隔 OR=0.79（0.70-0.89），p<0.001）、甲氨蝶呤（OR=0.54（0.29-0.98），p=0.044）、阿巴西普（OR=0.37（0.19-0.73），p=0.004）和 DMARD 数量（OR=0.55（0.33-0.90），p=0.018）。关于 NAb，年龄（每 5 岁间隔 OR=0.87（0.78-0.96），p=0.007）和泼尼松>7.5mg/天（OR=0.38（0.19-0.74），p=0.004）与 NAb 存在呈负相关。进一步比较 RA 治疗亚组和 CG 的 SC/NAb 阳性率显示，甲氨蝶呤/托法替尼/阿巴西普/托珠单抗单药或联合使用导致应答降低（p<0.05），而肿瘤坏死因子抑制剂和其他传统合成 DMARD 仅在联合其他疗法时受到干扰。
结论
接受 DMARD 治疗的 RA 患者对科兴疫苗具有中等的免疫原性。我们发现，几乎所有的 DMARD 联合治疗都会对免疫原性产生有害影响，而一些更有限的药物（甲氨蝶呤/托法替尼/阿巴西普/托珠单抗）作为单药治疗也会阻碍这种反应。这些发现强调了需要采取更广泛的方法，而不仅仅是特定药物，来提高这一人群的疫苗反应。
试验注册详情
NCT04754698。
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