SARS-CoV-2 has certainly been at the forefront of medical discussion and research for the past 3 years. While many are adjusting back to “normal,” thanks to the rapid advancements in prevention and treatment, high-risk groups, such as adults with systemic autoimmune rheumatic diseases (SARDs), still require careful monitoring and care. In the abundance of literature surrounding SARS-CoV-2, there remains a paucity of data specific to treatment of SARS-CoV-2 in patients with SARD.
Patients with SARD are known to have worse outcomes from SARS-CoV-2, including higher rates of hospitalization and, in some cases, higher mortality. Those with more comorbidities, older age, and more severe SARD manifestations are at the highest risk for poor outcomes.1-6 Although vaccination remains the best defense against the virus, patients with SARD may have a blunted response to the vaccine.7-11 Breakthrough infections in patients with SARD have been described.12 Booster doses are significantly helpful in this group, have been shown to reduce breakthrough infections,13 and continue to show benefit with new SARS-CoV-2 subvariants.14 Monoclonal antibodies have been helpful for those with infection who do not have detectable antibodies15; however, they have not shown to be effective in newer subvariants. Antiviral medications, including molnupiravir and nirmatelvir/ritonavir, do seem to retain effectiveness against these variants.16 Considering this, it is important to understand appropriate use of these antiviral medications in patients with SARD.
Molnupiravir and nirmatelvir/ritonavir are antiviral treatments for mild to moderate SARS-CoV-2 to prevent progression to severe disease in high-risk individuals. Patients with SARD frequently fall into this high-risk group because many are on immunosuppressive agents. Since initial approval, there have been a few studies that have examined antiviral use as it pertains to this population. Fragoulis et al described a case series of primarily vaccinated patients with SARD treated with oral antivirals, with none of the 31 patients requiring hospitalization and with no major safety concerns.17 Najjar-Debbiny et al demonstrated nirmatelvir/ritonavir has similar efficacy in vaccinated and unvaccinated individuals, and, although not directly examining patients with SARD, nirmatelvir/ritonavir was favored for patients on immunosuppression in a subgroup analysis.18 Potential concerns have been raised, however, regarding coronavirus disease 2019 (COVID-19) rebound in patients receiving antivirals, as well as concerns over drug-drug interactions. COVID-19 rebound occurs when the patient experiences recurrent COVID-19 infection and symptoms after completing a full course of antiviral therapy with symptom resolution. Wang et al have examined this in a preprint report that looked at patients taking molnupiravir or nirmatelvir/ritonavir.19 They found rebound rates ranging from 3.53% to 8.59%, with no statistically significant difference in rebound between the 2 agents, but with higher rebound rates in immunosuppressed patients. The need for hospitalization due to COVID-19 rebound was low in this study, at under 1.5%.19
In this issue of The Journal of Rheumatology, Gerolymatou et al retrospectively reviewed 74 patients with SARD who had received either molnupiravir or nirmatelvir/ritonavir for COVID-19 between February and August 2022, corresponding to the Omicron wave.20 Most patients were vaccinated with 3 doses of mRNA-based vaccines. Ninety-seven percent of patients recovered at home without complications, whereas 2 patients progressed to severe COVID-19, requiring hospitalization and high-flow nasal cannula supplemental oxygen. Both patients recovered and were subsequently discharged. The Discussion mentions these may have been COVID-19 rebound cases; however, it is not clear they had symptom improvement and subsequent recurrence prior to admission, as is seen in rebound cases, and rather likely had progression of their primary COVID-19 infection to severe disease. Overall, tolerability of antivirals in this patient group was very good, with only 4 patients reporting side effects and no patients discontinuing the drug. Although the side effect profile is desirable, drug-drug interactions are still a concern, especially with nirmatelvir/ritonavir, which can interact with CYP3A-dependent drugs, including tacrolimus, cyclosporine, and sirolimus.21
Gerolymatou et al20 mention that patients vaccinated and boosted with the Omicron variant may recover without event regardless of antiviral use due to vaccination status alone, as suggested by prior studies.13,22 Molnupiravir in particular may not reduce hospitalization rates in vaccinated patients as demonstrated by the PANORAMIC trial23 and by Yip et al.24 Nirmatelvir/ritonavir, however, does seem to confer benefit for vaccinated individuals.18,24 In line with this, Qian et al’s preprint study looking at 704 patients with SARD with COVID-19 from January 2022 through May 2022 showed nirmatelvir/ritonavir was beneficial in this patient population in reducing hospitalization or death from severe COVID-19. Importantly, most patients were vaccinated in this study.25
Overall, oral antiviral therapy for SARS-CoV-2, particularly nirmatelvir/ritonavir, is a good treatment option for patients with SARD. These medications have been shown to be safe and effective in reducing progression to severe COVID-19 but may have risk of COVID-19 rebound and have known drug-drug interactions. They also appear to remain effective despite Omicron subvariant emergence. Providers should be familiar with these treatment options for their patients with SARD who develop SARS-CoV-2 and should also continue to encourage patients with SARD to become fully vaccinated and boosted against COVID-19.
Footnotes
The authors have declared no conflicts of interest relevant to this article.
See Oral antivirals for COVID-19, page 1078
- Copyright © 2023 by the Journal of Rheumatology
