New data offer 'first glimpse' of COVID-19 vaccine efficacy in IMIDs, rheumatic diseases
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Emerging data are showing solid efficacy and safety of COVID-19 vaccines in individuals with rheumatic and immune-mediated diseases, according to a presentation at the United Rheumatology Spring Virtual conference.
“Several handfuls of papers have come out in the last 3 weeks,” Leonard Calabrese, DO, RJ Fasenmyer Chair of the Center for Clinical Immunology at Cleveland Clinic, said in his presentation. “They have given us the first glimpse of efficacy and safety in a few patients.”
While Calabrese spent significant time on the topic of vaccines, he stressed that some combination of vaccination and antiviral therapy will be necessary to ultimately contain COVID-19, particularly with variant strains emerging.
Cautious optimism
In the study by Geisen and colleagues in Annals of Rheumatic Diseases, a German cohort of 42 patients with a “mixed bag” of immune-mediated diseases (IMIDs) — “mostly rheumatoid arthritis,” according to Calabrese — provided reason for cautious optimism. “The 30,000-foot view is that their vaccine responses were in the same ballpark as controls,” he said. “But clearly nothing definitive can be concluded yet.”
One reason for this is that the results were assessed only after the first dose. But this is not the only study that Calabrese found intriguing.
Deepak and colleagues in their study in medRxiv provided the “first frame of what will be a moving picture of vaccine efficacy in our patients,” according to Calabrese. Findings showed that patients were producing antibodies after mRNA vaccines. “By and large, when you look in aggregate, people are making responses,” he said.
However, Calabrese acknowledged that, compared with controls, there is a “knockdown” in the response among individuals with connective tissue and chronic inflammatory diseases.
Looking deeper, Calabrese noted that, as expected, “B-cell depleting therapies are the greatest concern as most patients do not appear to respond with meaningful antibody responses when vaccinated within 6 months of treatment.” Unknown, however, is whether they are capable of mounting a meaningful cellular response that offers protection. “Further studies are urgently needed,” he said.
Perhaps more concerning because of their widespread use are glucocorticoids which, based on the study of Deepak and colleagues, appear to significantly inhibit antibody responses even at low doses. “In that same study, while the numbers were small, there was also a suppressive signal with JAK inhibitors which needs more detailed assessment,” Calabrese said.
Regarding other drugs in the rheumatology armamentarium, TNF inhibitors “do not seem to do much” to vaccine efficacy, according to Calabrese. He added that the same seems to be true, so far, for anti-integrin therapy and interleukin-12/23 therapies.
“Not everybody is going to respond, but there are enough data to show that there is reason enough for people to get vaccinated,” Calabrese said.
But more data are necessary, given that among the tens of thousands of patients who received the vaccines during clinical trials, patients with IMIDs were not represented at all. “Thus, making conclusions regarding efficacy and safety does not apply equally,” Calabrese said. “We go into this with our eyes open.”
If there is a final consideration on the vaccine front, it pertains to the COVID-19 variants currently circulating worldwide. “The most important thing we know is that our vaccines are highly effective against this,” he said. “However, there are some trials done in South Africa where there was a lower response to variants.”
The reason for this reduced response is not currently clear at the moment. It is important for rheumatologists to stay up to date on vaccine-related findings as they emerge, Calabrese said.
Antivirals and variants
“The next time I talk to you, we will be talking about antiviral therapy,” Calabrese said. “Which is a huge area of unmet need.”
Calabrese provided an overview of how the virus enters the cell, unpackages the single strand of RNA, creates proteins and then coopts the endoplasmic reticulum to encrypts RNA to make new viral progeny.
“The new horizon is: How do we stop this?” Calabrese said.
Inhibiting the replication may be one approach. “Poisoning” the process by using drugs similar to azidothymidine is another, according to Calabrese. “This is moving along very rapidly right now,” he said. “I think there will be some interesting data by the third quarter of 2021.”
While the world awaits herd immunity and an effective antiviral therapy, Calabrese urged rheumatologists to continue to treat their patients. “Having a well-controlled rheumatic disease puts you in a better position to cope with this infection,” he said.
As for specific diseases and how COVID-19 affects those patients, there is “no smoking gun,” Calabrese added. Patients with conditions ranging from RA and the psoriatic diseases to lupus and vasculitis all fare about the same, provided their disease is properly managed.
Overall, Calabrese urged ongoing vigilance. “We have to pay attention to what is going around our country right now,” he said. “We will have to retool if these variants take hold.”
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Calabrese L. COVID-19 in the Vaccine Era: What Rheumatologists Want to Know. Presented at: United Rheumatology Spring Virtual Conference; April 16-17, 2021.
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