Adalimumab and Infliximab Impair SARS-CoV-2 Antibody Responses: Results from a Therapeutic Drug Monitoring Study in 11 422 Biologic-Treated Patients.
Adalimumab and Infliximab Impair SARS-CoV-2 Antibody Responses: Results from a Therapeutic Drug Monitoring Study in 11 422 Biologic-Treated Patients.
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DOI：
10.1093/ecco-jcc/jjab153
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发表时间：
2022-03-14
期刊：
影响因子：
--
通讯作者：
Ahmad T
中科院分区：
文献类型：
--
作者：
Chanchlani N;Lin S;Chee D;Hamilton B;Nice R;Arkir Z;Bewshea C;Cipriano B;Derikx LAAP;Dunlop A;Greathead L;Griffiths RL;Ibraheim H;Kelleher P;Kok KB;Lees CW;MacDonald J;Sebastian S;Smith PJ;McDonald TJ;Irving PM;Powell N;Kennedy NA;Goodhand JR;Ahmad T
英夫利西单抗减弱SARS-CoV-2感染的血清学应答这是否是类效应，或者抗肿瘤坏死因子[抗TNF]水平是否影响血清学应答，仍不清楚。在2020年1月29日至9月30日期间储存在六个治疗药物监测实验室的11422名（53.3% [6084]男性;中位年龄36.8岁）免疫介导的炎症性疾病患者的剩余血清中测量了血清阳性率和SARS-CoV-2核衣壳抗体反应的幅度。数据与截至2021年7月11日的全国SARS-CoV-2 PCR结果相关联。PCR证实的SARS-CoV-2感染率在治疗组之间相似。英夫利西单抗和阿达木单抗治疗患者的血清阳性率低于Vedolizumab治疗患者（英夫利西单抗：3.0% [178/5893]，阿达木单抗：3.0% [152/5074]，Vedolizumab：6.7% [25/375]，p = 0.003）。 英夫利西单抗与阿达木单抗治疗患者的SARS-CoV-2反应程度相似（中位数4.30临界指数[COI] [1.94-9.96] vs 5.02 [2.18-18.70]，p = 0.164），但Vedolizumab治疗患者的SARS-CoV-2反应程度较高（中位数21.60 COI [4.39-68.10，p <0.004）。 与可检测到英夫利西单抗和阿达木单抗药物水平的患者相比，无法检测到药物水平[<0.8 mg/L]的患者更有可能出现SARS-CoV-2抗体血清阳性。在抗体检测前进行PCR检测的患者中，有三分之一未能发生血清转化，所有患者均接受了抗TNF治疗。中位时间为183.5天[129.8-235.3]后，7.9% [12/152]的患者出现后续PCR证实的SARS-CoV-2阳性，药物之间无差异。与Vedolizumab治疗的患者相比，抗TNF治疗与较低的SARS-CoV-2核衣壳血清阳性率和抗体反应性相关。尽管混杂因素（如与免疫调节剂联合治疗）可能影响结果，但抗TNF水平不可检测的患者的血清阳性率较高，支持因果关系。
Infliximab attenuates serological responses to SARS-CoV-2 infection. Whether this is a class effect, or if anti-tumour necrosis factor [anti-TNF] level influences serological responses, remains unknown. Seroprevalence and the magnitude of SARS-CoV-2 nucleocapsid antibody responses were measured in surplus serum from 11 422 (53.3% [6084] male; median age 36.8 years) patients with immune-mediated inflammatory diseases, stored at six therapeutic drug monitoring laboratories between January 29 and September 30, 2020. Data were linked to nationally held SARS-CoV-2 PCR results to July 11, 2021. Rates of PCR-confirmed SARS-CoV-2 infection were similar across treatment groups. Seroprevalence rates were lower in infliximab- and adalimumab- than vedolizumab-treated patients (infliximab: 3.0% [178/5893], adalimumab: 3.0% [152/5074], vedolizumab: 6.7% [25/375], p = 0.003). The magnitude of SARS-CoV-2 reactivity was similar in infliximab- vs adalimumab-treated patients (median 4.30 cut-off index [COI] [1.94–9.96] vs 5.02 [2.18–18.70], p = 0.164), but higher in vedolizumab-treated patients (median 21.60 COI [4.39–68.10, p < 0.004). Compared to patients with detectable infliximab and adalimumab drug levels, patients with undetectable drug levels [<0.8 mg/L] were more likely to be seropositive for SARS-CoV-2 antibodies. One-third of patients who had PCR testing prior to antibody testing failed to seroconvert, all were treated with anti-TNF. Subsequent positive PCR-confirmed SARS-CoV-2 was seen in 7.9% [12/152] of patients after a median time of 183.5 days [129.8–235.3], without differences between drugs. Anti-TNF treatment is associated with lower SARS-CoV-2 nucleocapsid seroprevalence and antibody reactivity when compared to vedolizumab-treated patients. Higher seropositivity rates in patients with undetectable anti-TNF levels support a causal relationship, although confounding factors, such as combination therapy with a immunomodulator, may have influenced the results.
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DOI：
10.2807/1560-7917.es.2021.26.20.2100428
发表时间：
2021-05
期刊：
Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin
影响因子：
--
作者：
Hodgson D;Flasche S;Jit M;Kucharski AJ;CMMID COVID-19 Working Group;Centre for Mathematical Modelling of Infectious Disease (CMMID) COVID-19 Working Group
通讯作者：
Centre for Mathematical Modelling of Infectious Disease (CMMID) COVID-19 Working Group
影响因子：
27.4
作者：
Park, Jin Kyun;Lee, Min Ah;Lee, Eun Bong
通讯作者：
Lee, Eun Bong
影响因子：
29.4
作者：
Wong SY;Dixon R;Martinez Pazos V;Gnjatic S;Colombel JF;Cadwell K;ICARUS-IBD Working Group
通讯作者：
ICARUS-IBD Working Group
影响因子：
27.4
作者：
Salinas, Gabriela Franco;De Rycke, Leen;Baeten, Dominique
通讯作者：
Baeten, Dominique
影响因子：
7.6
作者：
Casteele, N. Vande;Buurman, D. J.;Dijkstra, G.
通讯作者：
Dijkstra, G.