Real-world evidence for prehospital COVID-19 treatment in systemic autoimmune rheumatic disease

The impact of COVID-19 is regressing. As society begins to return to pre-pandemic norms, there remains a small but important population in whom COVID-19 is a concern, which includes patients with systemic autoimmune rheumatic disease. These patients were at increased risk of severe COVID-19 during the pandemic,¹ and current evidence suggests that they continue to be at risk of adverse outcomes. A major evolution in the management of COVID-19 is the use of direct antivirals and monoclonal antibodies. When used early in the disease course, these therapies are highly effective in reducing symptom duration and preventing disease progression. However, patients with systemic autoimmune rheumatic disease receiving immunomodulation have been excluded from antiviral or monoclonal antibody clinical trials. We are thus reliant on real-world evidence to understand the effect of these treatment strategies in patients with systemic autoimmune rheumatic disease.

In The Lancet Rheumatology, Grace Qian and colleagues² report the findings of a retrospective cohort study that evaluated outpatient SARS-CoV-2 treatment with antivirals or monoclonal antibodies in 704 patients with systemic autoimmune rheumatic disease and COVID-19 (mean age 58·4 years [SD 15·9]; 536 [76%] were female and 168 [24%] were male, and 590 [84%] were White and 39 [6%] were Black). The authors compared the subsequent risk of hospitalisation or death (severe COVID-19 outcomes; within 30 days of the first positive test) in patients who received outpatient SARS-CoV-2 treatment versus those who received no outpatient treatment. There were nine (2·1%) hospitalisations or deaths among 426 patients who received outpatient treatment compared with 49 (17·6%) among 278 who did not receive outpatient treatment (odds ratio [adjusted for age, sex, race, comorbidities, and kidney function] 0·12, 95% CI 0·05–0·25). Based on the absolute differences observed, about six patients would need to be treated to prevent one severe outcome.

When considering these impressive findings by Qian and colleagues,² we must acknowledge that associations reported in observational studies are not completely explained by causal relationships and are subject to confounding. The observed efficacy of antiviral or monoclonal antibody therapy reflects not only administration of the drug, but also the type of patient who is offered the drug. For example, there might be differences between patients who present soon after the onset of their COVID-19 symptoms compared with those who delay notifying their health-care provider of an infection. Although the authors addressed some of these factors in their adjusted model, unmeasured confounding was likely to still be present. Another important caveat is that this study was not powered to compare efficacy between different treatment strategies. The focus was on clinical decision to treat rather than the benefit of different drugs. When considering prehospital treatment options, one should recognise that the efficacy of monoclonal antibodies is highly dependent on the circulating SARS-CoV-2 variants, and this will influence prescribing preferences. Despite its limitations, this study provides very strong support for outpatient SARS-CoV-2 treatment in patients with systemic autoimmune rheumatic disease and COVID-19.

The study by Qian and colleagues² raises an essential question regarding COVID-19 rebound. Patients who are immunosuppressed, particularly with CD20 inhibitors, can have rebound COVID-19 symptoms and viral replication despite treatment with antivirals. This has been reported after remdesivir treatment in patients with immunosuppression early in the pandemic,³ and is also a focus of attention with nirmatrelvir–ritonavir treatment in people without immunosuppression.⁴ It remains unclear whether the risk of COVID-19 rebound is drug specific, but the data reported here certainly suggest the risk is greater among patients with immunosuppression. In this population, an extended course of antiviral treatment might be beneficial, and this is an area that deserves further study.

We now have robust evidence that early treatment of COVID-19 reduces the risk of hospitalisation among patients with systemic autoimmune rheumatic disease. As COVID-19 diminishes as a spectre in health care, we should focus on other established viral illnesses, such as influenza, which cause substantial morbidity and mortality among patients who are immunosuppressed. The progress made during the pandemic will enable us to revisit how we most effectively manage some of our older foes.

© 2023 Juan Gaertner/Science PhotoLibrary/Getty Images

KB and JG report institutional funding from Gilead. JG reports personal fees from Abbvie, Biovitrum, Celgene, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, Roche, and UCB.