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The effect of methotrexate and targeted immunosuppression on humoral and cellular immune responses to the COVID-19 vaccine BNT162b2: a cohort study.
Mahil, Satveer K; Bechman, Katie; Raharja, Antony; Domingo-Vila, Clara; Baudry, David; Brown, Matthew A; Cope, Andrew P; Dasandi, Tejus; Graham, Carl; Lechmere, Thomas; Malim, Michael H; Meynell, Freya; Pollock, Emily; Seow, Jeffery; Sychowska, Kamila; Barker, Jonathan N; Norton, Sam; Galloway, James B; Doores, Katie J; Tree, Timothy I M; Smith, Catherine H.
  • Mahil SK; St John's Institute of Dermatology, Guy's and St Thomas' NHS Foundation Trust, King's College London, London, UK.
  • Bechman K; Centre for Rheumatic Diseases, King's College London, London, UK.
  • Raharja A; St John's Institute of Dermatology, Guy's and St Thomas' NHS Foundation Trust, King's College London, London, UK.
  • Domingo-Vila C; Department of Immunobiology, Faculty of Life Sciences & Medicine, King's College London, London, UK.
  • Baudry D; St John's Institute of Dermatology, Guy's and St Thomas' NHS Foundation Trust, King's College London, London, UK.
  • Brown MA; Centre for Rheumatic Diseases, King's College London, London, UK.
  • Cope AP; Centre for Rheumatic Diseases, King's College London, London, UK.
  • Dasandi T; St John's Institute of Dermatology, Guy's and St Thomas' NHS Foundation Trust, King's College London, London, UK.
  • Graham C; Department of Infectious Diseases, School of Immunology and Microbial Sciences, King's College London, London, UK.
  • Lechmere T; Department of Infectious Diseases, School of Immunology and Microbial Sciences, King's College London, London, UK.
  • Malim MH; Department of Infectious Diseases, School of Immunology and Microbial Sciences, King's College London, London, UK.
  • Meynell F; St John's Institute of Dermatology, Guy's and St Thomas' NHS Foundation Trust, King's College London, London, UK.
  • Pollock E; Department of Immunobiology, Faculty of Life Sciences & Medicine, King's College London, London, UK.
  • Seow J; Department of Infectious Diseases, School of Immunology and Microbial Sciences, King's College London, London, UK.
  • Sychowska K; Department of Immunobiology, Faculty of Life Sciences & Medicine, King's College London, London, UK.
  • Barker JN; St John's Institute of Dermatology, Guy's and St Thomas' NHS Foundation Trust, King's College London, London, UK.
  • Norton S; Psychology Department, Institute for Psychiatry Psychology and Neuroscience, King's College London, London, UK.
  • Galloway JB; Centre for Rheumatic Diseases, King's College London, London, UK.
  • Doores KJ; Department of Infectious Diseases, School of Immunology and Microbial Sciences, King's College London, London, UK.
  • Tree TIM; Department of Immunobiology, Faculty of Life Sciences & Medicine, King's College London, London, UK.
  • Smith CH; St John's Institute of Dermatology, Guy's and St Thomas' NHS Foundation Trust, King's College London, London, UK.
Lancet Rheumatol ; 3(9): e627-e637, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1301109
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.

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.

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.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.

FUNDING:

UK National Institute for Health Research.

Full text: Available Collection: International databases Database: MEDLINE Type of study: Etiology study / Observational study / Randomized controlled trials Topics: Vaccines / Variants Language: English Journal: Lancet Rheumatol Year: 2021 Document Type: Article Affiliation country: S2665-9913(21)00212-5

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Full text: Available Collection: International databases Database: MEDLINE Type of study: Etiology study / Observational study / Randomized controlled trials Topics: Vaccines / Variants Language: English Journal: Lancet Rheumatol Year: 2021 Document Type: Article Affiliation country: S2665-9913(21)00212-5