Oral Antivirals Have Acceptable Safety Profile in Patients With Rheumatic Diseases

Two oral antivirals – molnupiravir and nirmatrelvir/ritonavir – were found to be safe and effective among high-risk patients with systemic autoimmune rheumatic diseases (SARDs), according to study findings published in The Journal of Rheumatology.

Researchers in Greece conducted a retrospective observational cohort study across 2 tertiary outpatient rheumatology clinics between February and August 2022. The safety and efficacy of molnupiravir and nirmatrelvir/ritonavir were assessed among patients with SARDs who were infected with COVID-19.

A total of 83.8% (n=62) of the cohort was fully vaccinated against COVID-19. Corticosteroids (58.1%), mycophenolate (35.1%), tumor necrosis factor inhibitors (TNFi; 18.9%), methotrexate (17.6%), and rituximab (16.2%) were among the most commonly used treatments for SARD before infection with SARS-CoV-2.

During acute COVID-19 infection, most patients (n=48; 64.9%) received nirmatrelvir/ritonavir, while the remaining received molnupiravir (n=26; 35.1%). Four patients who received treatment with nirmatrelvir/ritonavir reported adverse events, including gastrointestinal upset, hypertension, and a metallic taste; however, none of these events were serious enough to discontinue treatment.

During the follow-up period, 97.3% (n=72) of the patients recovered from COVID-19 at home without complications, while the other 2 patients presumably experienced COVID-19 rebound, which progressed to severe COVID-19, following completion of the oral antiviral treatment. Both these patients required high-flow nasal cannula ventilation, remdesivir, steroids, antibiotic therapy, and tocilizumab to treat severe respiratory distress.

Both patients with COVID-19 rebound survived. One resolved uneventfully, while the other continued to test positive for COVID-19 more than 3 months after the initial infection resolved, despite not having relevant symptoms.

Study limitations included the retrospective and observational design, potential missed patients with asymptomatic or mild COVID-19 infections who did not self-refer or attend a routine physical exam, lack of a control group for comparison because less than 10 patients refused oral antiviral treatment, and potential recall bias regarding side effects of the medications and confusion of drug side effects with COVID-19 symptoms.

“[These] data [argue] in favor of a favorable outcome and acceptable safety profile of the [2] oral antiviral therapies among a high-risk SARD population; however, cases of COVID-19 rebound are being increasingly identified,” the study authors said. “Recent findings call for continuous surveillance and multicenter, harmonized and well-defined post-approval data to capture the real-world efficacy and safety profiles in our subpopulations of interest,” they added.