Methotrexate use tied to weakened antibody response after first Pfizer-BioNTech vaccine shot

Reuters Health - 21/07/2021 - The antibody, but not the T-cell, response to the first dose of the Pfizer SARS-CoV-2 vaccine is impaired in patients taking the immunosuppressant methotrexate, while both antibody and T-cell responses are preserved in patients taking targeted biologics such as anti-tumor necrosis factor (TNF) agents, new research suggests.

"Our data showing that the T-cell responses following the first dose of the Pfizer COVID-19 vaccine were not affected in those taking methotrexate or a biologic therapy - including in some of those who didn't seroconvert - is reassuring," the authors say in a statement from the European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) where the study was presented, with simultaneous publication in The Lancet Rheumatology.

"However, ongoing monitoring of these patients is needed to determine what this means for the clinical effectiveness of the vaccines," they add.

Dr. Satveer Mahil with Guy's and St. Thomas' NHS Foundation Trust, in London, and colleagues studied 84 patients with psoriasis receiving monotherapy with methotrexate, TNF inhibitors, interleukin (IL)-17 inhibitors or IL-23 inhibitors, and 17 healthy volunteers. None of the participants had a history of COVID-19.

The primary outcomes were humoral immunity to the SARS-CoV-2 spike glycoprotein, defined as neutralizing antibody responses to wild-type SARS-CoV-2, and spike-specific T-cell responses 28 days after vaccination.

Patients taking immunosuppressant agents had lower rates of seroconversion. All 17 healthy volunteers had evidence of seroconversion, compared to 78% of those on immunosuppressants. Patients taking methotrexate had the lowest seroconversion rate at 47%.

In addition, neutralizing activity against wild-type SARS-CoV-2 was significantly lower in patients on methotrexate than in healthy volunteers (median 50% inhibitory dilution, 129 vs. 317; P=0.0032), but was preserved in those receiving targeted biologics (median 50% inhibitory dilution, 269).

"Neutralizing titers against the B.1.1.7 variant were similarly low in all participants, underlining the need to continue to take preventative measures after having the first dose of the vaccine, the authors say.

"Cellular immune responses were induced in all groups, and were not attenuated in patients receiving methotrexate or targeted biologics compared with controls," they add.

The team is awaiting data on the participants' humoral and cellular responses after second vaccine dose.

The current data, they say, add to ongoing concern over the efficacy of SARS-CoV-2 vaccines in immunocompromised patients.

The authors of a linked editorial say these patients might "remain vulnerable after the first dose" and should engage in risk mitigation strategies.

"Furthermore, given the promising findings after two-dose vaccination, we believe that both doses of the (Pfizer) vaccine should be administered per the approved schedule to reduce the burden of COVID-19 in this vulnerable population," write Dr. Caoilfhionn Connolly and Dr. Julie Park of the Division of Rheumatology, Johns Hopkins University School of Medicine, in Baltimore, Maryland.

"Patients receiving immunosuppressive therapies should be prioritized for the regular schedule of vaccination (not a prolonged interval between doses) and should be aware of the potential for suboptimal vaccine responses, even after completion of the vaccine series," they say.

"With the specter of variants looming, vaccination will allow patients to achieve maximum protection and reduce the burden of COVID-19. In the interim, there is a need for ongoing vigilance in observing non-pharmacological preventive measures in these patients," they conclude.

SOURCE: https://bit.ly/3wXcTOF and https://bit.ly/2UmtkHr Lancet Rheumatology, online July 8, 2021.

By Reuters Staff



Posted on 21 July 20213 August 2021