Diabetes Zentrum Mergentheim, Bad Mergentheim, Germany.
Medizinische Klinik und Poliklinik II, Klinikum der Universität Würzburg, Würzburg, Germany.
Clin Rheumatol. 2022 Dec;41(12):3707-3714. doi: 10.1007/s10067-022-06329-2. Epub 2022 Aug 15.
Recently, a number of studies have explored the possible attenuation of the immune response by disease-modifying antirheumatic drugs (DMARDs) in patients with rheumatoid arthritis (RA). Our study objective was to investigate the presumed attenuated humoral response to vaccination against SARS-CoV-2 in patients with RA treated with Janus kinase (JAK) inhibitors with or without methotrexate (MTX). The immune responses were compared with controls without RA.
The humoral vaccination response was evaluated by determining titres of neutralising antibodies against the S1 antigen of SARS-CoV-2. One hundred and thirteen fully vaccinated individuals were included at 6 ± 1 weeks after second vaccination (BioNTech/Pfizer (69.9%), AstraZeneca (21.2%), and Moderna (8.9%)). In a cross-sectional and single-centre study design, we compared titres of neutralising antibodies between patients with (n = 51) and without (n = 62) medication with JAK inhibitors.
Treatment with JAK inhibitors led to a significantly reduced humoral response to vaccination (P = 0.004). A maximum immune response was seen in 77.4% of control patients, whereas this percentage was reduced to 54.9% in study participants on medication with JAK inhibitors (effect size d = 0.270). Further subanalyses revealed that patients on combination treatment (JAK inhibitors and MTX, 9 of 51 subjects) demonstrated an even significantly impaired immune response as compared to patients on monotherapy with JAK inhibitors (P = 0.028; d = 0.267).
JAK inhibitors significantly reduce the humoral response following dual vaccination against SARS-CoV-2. The combination with MTX causes an additional, significant reduction in neutralising IgG titres. Our data suggest cessation of JAK inhibitors in patients with RA in the context of vaccination against SARS-CoV-2. Key Points • It was shown that DMARD therapy with JAK inhibitors in patients with rheumatoid arthritis leads to an attenuation of the humoral vaccination response against SARS-CoV-2. • The effect under medication with JAK inhibitors was significant compared to the control group and overall moderate. • The combination of JAK inhibitors with MTX led to an additive and significant attenuation of the humoral response.
最近，许多研究探讨了疾病修饰抗风湿药物（DMARDs）对类风湿关节炎（RA）患者免疫反应的可能抑制作用。我们的研究目的是探讨接受 Janus 激酶（JAK）抑制剂联合或不联合甲氨蝶呤（MTX）治疗的 RA 患者对 SARS-CoV-2 疫苗接种的假定减弱的体液免疫反应。将免疫反应与无 RA 的对照组进行比较。
通过测定针对 SARS-CoV-2 S1 抗原的中和抗体滴度来评估体液疫苗接种反应。在第二次接种后 6 ± 1 周，纳入了 113 名完全接种疫苗的个体（BioNTech/Pfizer（69.9%）、阿斯利康（21.2%）和 Moderna（8.9%））。在一项横断面和单中心研究设计中，我们比较了接受（n=51）和不接受（n=62）JAK 抑制剂治疗的患者之间中和抗体滴度。
JAK 抑制剂治疗导致疫苗接种后的体液反应显著降低（P=0.004）。在对照组患者中，最大免疫反应出现在 77.4%的患者中，而接受 JAK 抑制剂治疗的研究参与者中，这一比例降至 54.9%（效应大小 d=0.270）。进一步的亚分析显示，与接受 JAK 抑制剂单药治疗的患者相比，接受联合治疗（JAK 抑制剂和 MTX，51 名受试者中的 9 名）的患者免疫反应甚至显著受损（P=0.028；d=0.267）。
JAK 抑制剂显著降低了双重接种 SARS-CoV-2 后的体液反应。与 MTX 联合使用会导致中和 IgG 滴度进一步显著降低。我们的数据表明，在接种 SARS-CoV-2 疫苗时，RA 患者应停止使用 JAK 抑制剂。
研究表明，类风湿关节炎患者接受 DMARD 治疗联合 JAK 抑制剂会导致针对 SARS-CoV-2 的体液疫苗接种反应减弱。
与对照组相比，接受 JAK 抑制剂治疗的患者的效果显著，总体中等。
JAK 抑制剂联合 MTX 会导致体液反应的叠加和显著减弱。
