Editor’s note: The U.S. Food & Drug Administration’s emergency use authorizations are subject to change as circumstances evolve. Check current information on the FDA’s website.
When oral antiviral drugs for COVID-19 are available, use them early and as aggressively as possible, said Michael S. Saag, MD, professor of medicine at University of Alabama–Birmingham, at a virtual ACR town hall on Jan. 19, 2022. The immune system needs as much help as possible to get the SARS-CoV-2 virus under control in patients on immunosuppressive drugs, he added.
Dr. Saag
During the town hall, an expert panel discussed risk factors for poor COVID-19 outcomes, as well as the use of oral antiviral therapy for rheumatology patients with COVID-19. They also talked about monoclonal antibody therapy and the best use of vaccines. The panel included Dr. Saag, Monica Gandhi, MD, MPH, professor of medicine and associate chief of the division of HIV, infectious diseases and global medicine at the University of California, San Francisco, and Andrew T. Pavia, MD, adjunct professor of internal medicine, professor of pediatrics and chief of the division of pediatric infectious diseases at the University of Utah, Salt Lake City.
Timing Is Key
When considering which rheumatology patients are prone to poor COVID-19 outcomes, Dr. Saag suggested the natural course of COVID-19 should be considered. He explained that the initial four to seven days after SARS-CoV-2 infection is the viremic phase, when most patients exhibit symptoms and the innate immune response is triggered. The second phase, from days six to 14, is when the adaptive immune response is activated.
Rheumatic patients on immunosuppression have an inhibited adaptive response, setting them up for a prolonged viremic phase. “If glucocorticoids are prescribed in the first phase, viral replication is prolonged,” Dr. Saag said, calling this “a common mistake” that may lead to longer illness.
Dr. Pavia
Emerging data—mainly observational—suggest that immunosuppressive drugs confer different risks for poor COVID-19 outcomes and vaccine responses in immunocompromised patients, Dr. Pavia said. B cell-modifying drugs are associated with the highest risk, and tumor necrosis factor inhibitors appear to have the least impact on COVID-19 outcomes. Hydrocortisone, Janus kinase (JAK) inhibitors and mycophenolate fall in between, and azathioprine has shown conflicting results.
Other patient factors also matter, especially age. “For the same amount of immunosuppression, someone who is 75 is at a much higher risk than someone who is 35,” Dr. Pavia said.
Two oral antiviral drugs have received emergency use authorization (EUA) from the U.S. Food & Drug Administration, nirmatrelvir/ritonavir (Paxlovid) and molnupiravir. Dr. Pavia noted that nirmatrelvir/ritonavir, which is in short supply, has been shown to reduce the progression to hospitalization or death in high-risk patients by about 88% when given within five days.1 The drug has some potentially lethal interactions with cardiac medications and antipsychotics, but has shown fewer interactions with immunosuppressive drugs, apart from cyclosporine, tacrolimus and sirolimus. He recommended that clinicians review their patients’ medicines with a pharmacist or use Liverpool University’s drug interaction checker.2
Molnupiravir is not as effective as nirmatrelvir/ritonavir for the treatment of COVID-19, but it is in greater supply and does not have the same drug interactions. However, it is contraindicated for use in children and during pregnancy. Contraception is necessary for all patients while taking the drug and for three months afterward in men.
Prevention
Meanwhile, several monoclonal antibody therapies have been developed to help prevent COVID-19. Tixagevimab/cilgavimab (Evusheld) is the only monoclonal antibody therapy that has received an EUA for pre-exposure prophylaxis to prevent COVID-19, and it is effective against the omicron variant, Dr. Saag said. Bamlanivimab/etesevimab, casirivimab/imdevimab (REGEN-COV) and sotrovimab have received EUAs for post-exposure prophylaxis; however, only the last is effective against the omicron variant.
Tixagevimab/cilgavimab has been shown to prevent serious COVID-19 outcomes for up to six months with the delta variant, but its effectiveness will likely be shorter with the omicron variant, Dr. Pavia explained. Although it may still be promising for a few months, he noted tixagevimab/cilgavimab is in very short supply and that its use will be expanded to more patients as it becomes more readily available.
Dr. Gandhi
The expert panel agreed the booster vaccine dose should be a different type of vaccine from the initial series. A fourth dose for immunocompromised patients makes a lot of sense, Dr. Gandhi said; however, a fourth dose is not likely to be approved for immunocompetent individuals. “There’s a concept called original antigenic sin, which is the idea that if you keep on training your immune system to form T cells and antibodies against the ancestral strain … then you redirect your resources to not produce T cells and antibodies against the variant you see in front of you,” Dr. Gandhi explained.
Katie Robinson is a medical writer based in New York.
References
- Pfizer, Inc. Pfizer announces additional phase 2/3 study results confirming robust efficacy of novel COVID-19 oral antiviral treatment candidate in reducing risk of hospitalization or death. 2021 Dec 14.
- University of Liverpool. COVID-19 drug interactions.
