Immunotherapy drugs show ‘clear hierarchy’ of poor COVID-19 vaccine response
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Further research is needed to ‘deconvolute’ the risk of poor COVID-19 vaccine response in patients treated with immunomodulatory drugs, according to a presenter at the Basic and Clinical Immunology for the Busy Clinician symposium.
“There are two clear reasons why we need to protect the immunosuppressed from COVID-19,” Alfred Kim, MD, PhD, assistant professor in the division of medicine at the School of Medicine at Washington University in St. Louis, said in his presentation.
One is that that COVID-19 variants can emerge in these patients after prolonged exposure to the virus. But, perhaps more importantly for the practicing rheumatologist, is the reality that these patients are at increased risk for severe complications and death from the virus, largely due to immunosuppressive medications.
With that, Kim waded into the thorny territory of immunomodulatory drugs and COVID-19 vaccines. “There are attenuated humoral responses with the vaccine,” he said.
Kim acknowledged that patients taking a cross-section of drugs can mount “decent” humoral responses. “But risk is not uniformly distributed across immunotherapy classes that our patients take,” he said. “Rather a clear hierarchy has emerged.”
Unsurprisingly, data show that B-cell depleting therapies pose the highest risk for poor vaccine response. Kim suggested that these drugs may be associated with as much as a 50-fold reduction in antibody response.
“There is reduced proliferative capacity, reduced somatic hypermutation potential, reduced antibody diversity, reduced binding strength,” he said. “Also, memory B-cell generation is greatly impaired.”
Current research is looking at the impact of COVID-19 vaccines in patients treated with B cell depleting drugs over time. “The antibodies generated immediately after vaccination are different from those that emerge over time,” he said.
In short, researchers are still determining when to cease and restart B-cell drugs before and after COVID-19 vaccination.
Regarding glucocorticoids, Kim expressed surprise that even low doses yielded poor humoral responses to COVID-19 vaccines. While some data have shown that prednisone monotherapy did not associate with poor vaccine response, other data have indicated as much as a nine-fold reduction in humoral response in patients being treated with glucocorticoids.
For mycophenolate mofetil, a 21-fold decrease in antibody response to COVID-19 vaccines has been observed in comparison with immunocompetent controls, according to data from the COVaRiPAD study, from Deepak and colleagues in Annals of Internal Medicine.
“Methotrexate and azathioprine had much more modest reductions,” he said.
Similarly, biologic and targeted synthetic disease-modifying anti-rheumatic drugs also had a “modest” effect on antibody titers, according to Kim. Data have shown that janus kinase (JAK) inhibitors yielded a 2.6-fold reduction in response, while the reduction for TNF inhibition was just 2.3-fold.
The news for COVID-19 vaccination in the immunosuppressive setting is not all bad, however. “The good news is that boosting helps antibody titers,” Kim said.
But the impact of boosting in individual drugs and drug classes — along with the necessity and/or timing of drug cessation surrounding vaccination — needs to be further clarified. “Work still needs to be done to deconvolute the effect of multiple immunomodulatory medications and their association with antibody responses,” Kim said.
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Kim A. Vaccine response in IMIDS - challenges and strategies. Presented at Basic and Clinical Immunology for the Busy Clinician; Feb. 26, 2022. (virtual meeting).
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