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. 2021 Sep;3(9):e627-e637.
doi: 10.1016/S2665-9913(21)00212-5. Epub 2021 Jul 8.

"VSports手机版" The effect of methotrexate and targeted immunosuppression on humoral and cellular immune responses to the COVID-19 vaccine BNT162b2: a cohort study

Satveer K Mahil  1 , Katie Bechman  2 , Antony Raharja  1 , Clara Domingo-Vila  3 , David Baudry  1 , Matthew A Brown  2 , Andrew P Cope  2 , Tejus Dasandi  1 , Carl Graham  4 , Thomas Lechmere  4 , Michael H Malim  4 , Freya Meynell  1 , Emily Pollock  3 , Jeffery Seow  4 , Kamila Sychowska  3 , Jonathan N Barker  1 , Sam Norton  5 , James B Galloway  2 , Katie J Doores  4 , Timothy I M Tree  3 , Catherine H Smith  1
Affiliations

The effect of methotrexate and targeted immunosuppression on humoral and cellular immune responses to the COVID-19 vaccine BNT162b2: a cohort study (VSports手机版)

Satveer K Mahil et al. Lancet Rheumatol. 2021 Sep.

Abstract

Background: Patients on therapeutic immunosuppressants for immune-mediated inflammatory diseases were excluded from COVID-19 vaccine trials. We therefore aimed to evaluate humoral and cellular immune responses to COVID-19 vaccine BNT162b2 (Pfizer-BioNTech) in patients taking methotrexate and commonly used targeted biological therapies, compared with healthy controls. Given the roll-out of extended interval vaccination programmes to maximise population coverage, we present findings after the first dose VSports手机版. .

Methods: In this cohort study, we recruited consecutive patients with a dermatologist-confirmed diagnosis of psoriasis who were receiving methotrexate or targeted biological monotherapy (tumour necrosis factor [TNF] inhibitors, interleukin [IL]-17 inhibitors, or IL-23 inhibitors) from a specialist psoriasis centre serving London and South East England. Consecutive volunteers without psoriasis and not receiving systemic immunosuppression who presented for vaccination at Guy's and St Thomas' NHS Foundation Trust (London, UK) were included as the healthy control cohort. All participants had to be eligible to receive the BNT162b2 vaccine. Immunogenicity was evaluated immediately before and on day 28 (±2 days) after vaccination. The primary outcomes were humoral immunity to the SARS-CoV-2 spike glycoprotein, defined as neutralising antibody responses to wild-type SARS-CoV-2, and spike-specific T-cell responses (including interferon-γ, IL-2, and IL-21) 28 days after vaccination. V体育安卓版.

Findings: Between Jan 14 and April 4, 2021, 84 patients with psoriasis (17 on methotrexate, 27 on TNF inhibitors, 15 on IL-17 inhibitors, and 25 on IL-23 inhibitors) and 17 healthy controls were included. The study population had a median age of 43 years (IQR 31-52), with 56 (55%) males, 45 (45%) females, and 85 (84%) participants of White ethnicity. Seroconversion rates were lower in patients receiving immunosuppressants (60 [78%; 95% CI 67-87] of 77) than in controls (17 [100%; 80-100] of 17), with the lowest rate in those receiving methotrexate (seven [47%; 21-73] of 15). Neutralising activity against wild-type SARS-CoV-2 was significantly lower in patients receiving methotrexate (median 50% inhibitory dilution 129 [IQR 40-236]) than in controls (317 [213-487], p=0·0032), but was preserved in those receiving targeted biologics (269 [141-418]). Neutralising titres against the B V体育ios版. 1. 1. 7 variant were similarly low in all participants. Cellular immune responses were induced in all groups, and were not attenuated in patients receiving methotrexate or targeted biologics compared with controls. .

Interpretation: Functional humoral immunity to a single dose of BNT162b2 is impaired by methotrexate but not by targeted biologics, whereas cellular responses are preserved. Seroconversion alone might not adequately reflect vaccine immunogenicity in individuals with immune-mediated inflammatory diseases receiving therapeutic immunosuppression. Real-world pharmacovigilance studies will determine how these findings reflect clinical effectiveness. VSports最新版本.

Funding: UK National Institute for Health Research. V体育平台登录.

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Conflict of interest statement

CHS reports grants from AbbVie, Sanofi, Novartis, and Pfizer, outside the submitted work. JBG reports personal fees from AbbVie, Sanofi, Novartis, Pfizer, Janssen, and UCB, and grants from Eli Lilly, outside the submitted work. SKM reports departmental income from AbbVie, Celgene, Eli Lilly, Janssen-Cilag, Novartis, Sanofi, and UCB, outside the submitted work. MAB reports departmental income from Clementia, Eli Lilly, Ipsen, Novartis, Pathios Therapeutics, Regeneron, and UCB, outside the submitted work V体育官网入口. JNB reports grants and personal fees from AbbVie, Novartis, Lilly, and J&J, outside the submitted work. SN reports personal fees from Pfizer and Janssen, outside of the submitted work. APC reports grants from Bristol Myers Squibb and Janssen, and speaker bureau and consultancy fees from AbbVie, Bristol Myers Squibb, and UCB. TIMT reports grants from GlaxoSmithKline, Sanofi, and Imcyse, and consultancy fees from GlaxoSmithKline, Novartis, UCB, and Quell Therapeutics, outside the submitted work. All other authors declare no competing interests.

"VSports手机版" Figures

Figure 1
Figure 1
Study overview IL=interleukin. TNF=tumour necrosis factor.
Figure 2
Figure 2
Serological immune responses to COVID-19 vaccine BNT162b2 Spike-specific IgG titres (EC50) in plasma samples on day 28 after vaccination in healthy controls and patients with psoriasis receiving methotrexate or targeted biological monotherapy. The circles represent individual values. The red diamonds and range lines indicate the median and IQR. In the IL-23 inhibitor group, filled circles represent participants receiving IL-23p19 inhibitors and hollow circles represent participants receiving an IL-12/23p40 inhibitor. The horizontal dashed line indicates the seroconversion threshold. EC50=half maximal effective concentration. IL=interleukin. TNF=tumour necrosis factor.
Figure 3
Figure 3
Functional humoral immunogenicity of the COVID-19 vaccine BNT162b2 (A) Neutralisation titres against wild-type SARS-CoV-2 on day 28 after the first dose of BNT162b2. (B) Neutralisation titres against B.1.1.7 SARS-CoV-2 variant on day 28 after the first dose of BNT162b2. The circles represent individual values. The red diamonds and range lines indicate the median and IQR. In the IL-23 inhibitor group, filled circles represent participants receiving IL-23p19 inhibitors and hollow circles represent participants receiving an IL-12/23p40 inhibitor. The horizontal dashed line indicates neutralisation activity threshold. (C) Correlation between spike-specific IgG and neutralisation titres against wild-type or the B.1.1.7 variant. Blue diamonds show individual patients, shading indicates the 95% CI. EC50=half maximal effective concentration. ID50=50% inhibitory dilution. IL=interleukin. TNF=tumour necrosis factor.
Figure 4
Figure 4
Cellular immunogenicity of the COVID-19 vaccine BNT162b2 (A) Total T-cell response, as determined by combined interferon-γ, IL-2, and IL-21 responses to stimulation with peptides from total spike peptide pools, reported as number of cytokine-secreting cells per 106 cells in PBMC samples on day 28 after the first dose of BNT162b2. The horizontal line indicates the T-cell response threshold. (B) IL-17A and IL-22 responses to stimulation with peptides from total spike peptide pools, reported as number of cytokine-secreting cells per 106 cells in PBMC samples on day 28 after the first dose of COVID-19 vaccine BNT162b2. The horizontal line indicates the T helper 17 response threshold. The circles represent individual values. The red diamonds and range lines indicate the median and IQR. In the IL-23 inhibitor group, filled circles represent participants receiving IL-23p19 inhibitors and hollow circles represent participants receiving an IL-12/23p40 inhibitor. (C) Spearman correlation between T-cell responses (cytokine-secreting cells per 106 PBMCs) and humoral immune responses as determined by ELISA and neutralisation assays. The colour scale indicates the Spearman R values; all p values are less than 0·01. EC50=half maximal effective concentration. ID50=50% inhibitory dilution. IL=interleukin. PBMCs=peripheral blood mononuclear cells. TNF=tumour necrosis factor.
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