Biologic drug makes recurrent COVID infection more likely

Pharma News: A powerful biologic that is used to treat inflammatory bowel disease (IBD) blunts the body’s immune response to COVID-19 infection, according to research published in the journal Gut.

The impaired response caused by infliximab (Janssen’s Remicade, Pfizer’s Inflectra or Organon’s Renflexis) may boost susceptibility to recurrent COVID-19 and help drive the evolution of new variants of SARS-CoV-2, warn the researchers.

Careful monitoring of IBD patients treated with infliximab will be needed after vaccination against COVID-19 to ensure they mount a strong enough antibody response to ward off the infection.

Researchers compared the antibody responses to SARS-CoV-2 in IBD patients treated with infliximab or Takeda’s Entyvio (vedolizumab).

Vedolizumab is a gut monoclonal antibody that has a dosing schedule similar to that of infliximab. But it isn’t associated with increased susceptibility to systemic infection or blunted immune responses to vaccination.

In all, 6,935 IBD patients (average age 39) were recruited from 92 UK hospitals between September and December 2020 for the CLARITY IBD study: around two thirds (4,685) of them were being treated with infliximab and around a third (2,250) with vedolizumab.

Only around half (48%; 39/81) of the patients treated with infliximab whose COVID-19 infection was confirmed by a swab test subsequently developed antibodies compared to 83% (30/36) of those treated with vedolizumab.

The addition of other commonly used drugs to dampen down the inflammatory response, such as thiopurine or methotrexate, further blunted the antibody response to SARS-CoV-2 in patients treated with infliximab, only a third of whom had detectable antibodies to SARS-CoV-2.

An increase in antibodies to SARS-CoV-2 was observed 4 weeks after a positive swab test in patients taking vedolizumab, but not in those treated with infliximab.

“Similar rates of symptomatic and proven SARS-CoV-2 infection and hospitalisations between infliximab-treated and vedolizumab-treated patients suggest that our findings cannot be explained by differences in acquisition or severity of infection alone. Rather, infliximab seems to be directly influencing the serological response to infection,” explain the researchers.

“Infliximab may directly impede the immune mechanisms responsible for generating antibody responses,” the authors suggest.

This is an observational study, and so can’t establish cause. Nevertheless, the researchers suggest that a weakened antibody response has potentially far reaching implications.

“It may increase susceptibility to recurrent COVID-19 in patients treated with infliximab, which might then lead to chronic colonisation of the virus in the nose and throat. This “may act as a reservoir to drive persistent transmission and the evolution of new SARS-CoV-2 variants,” they warn.

The authors conclude “Serological testing and virus surveillance should be considered to detect suboptimal vaccine responses, persistent infection, and viral evolution to inform public health policy. If attenuated serological responses following vaccination are also observed, then modified immunisation strategies will need to be designed for millions of patients worldwide.”

The study was funded by Roche, Biogen, Celltrion and Galapagos.