Paxlovid Reduces Short and Long-Term Adverse Outcomes in COVID-19 Patients with Kidney Disease

A recent study published in Open Forum Infectious Diseases demonstrates that nirmatrelvir-ritonavir (Paxlovid), an antiviral treatment for COVID-19, significantly reduces short- and long-term adverse outcomes in patients with kidney disease. This cohort study involved 1,095 patients with kidney disease who received Paxlovid, compared to 584 patients diagnosed with COVID-19 before the treatment's introduction.¹

The results revealed that Paxlovid-treated patients were 56% less likely to be hospitalized within 30 days of diagnosis (adjusted subdistribution hazard ratio (sHR) .44, p<.01). Additionally, at one year, these patients had a significantly lower risk of hospitalization due to major adverse cardiovascular events (MACE) (adjusted sHR .49, p<.01) and death (adjusted hazard ratio (aHR) .37, p<.01). Although, the treatment did not show an impact on the progression of chronic kidney disease (CKD) or the rate of eGFR decline over the year following infection.¹

This study underscores the potential benefits of Paxlovid in reducing hospitalizations and mortality in patients with CKD and kidney failure, though it does not prevent CKD progression. These findings highlight the need for continued research into the optimal management of COVID-19 in this vulnerable population.¹

To understand the rationale behind studying this population, author Ian Austin Strohbehn, lab manager at the Sise Lab at the Onconephrology Group at Massachusetts General Hospital shared key insights with Contagion into why patients with advanced kidney disease were often excluded from registrational clinical trials, a limitation that impacts the broader applicability of these findings.

"It’s extremely common that patients with advanced CKD and kidney failure are excluded from registrational clinical trials," Strohbehn explained. "This may be because a medication is renally cleared from the body, so reduced kidney function would affect drug levels and potentially increase the side effect risk of a medication. Or it may be that these patients are considered higher risk for adverse outcomes, thus not an ideal clinical trial patient."

Although, Strohbehn noted that this exclusion of high-risk patients presents a gap in understanding how these interventions could benefit the very groups most vulnerable to severe outcomes. “These patients are often at highest risk from the conditions being studied, and thus could disproportionately benefit from interventions. We know, for instance, that both before and after widespread vaccination, patients with kidney disease were at high risk for adverse outcomes and death from COVID-19. It is therefore very important to study whether or not interventions can be safely used in this population.” To address this gap, the recent study used observational data to assess treatment outcomes by comparing propensity-score matched patients who either did or did not receive nirmatrelvir-ritonavir.

Efficacy Across Different Stages of CKD

Another area of interest was whether the efficacy of Paxlovid varied across different stages of kidney disease. When asked about this, Strohbehn confirmed that no significant differences were found. "The effects were consistent between stage 3A (eGFR 45-60) and stage 3B/4/5 patients (eGFR < 45),” he said. "This is shown in Supplemental Table S3 in the paper."

This finding suggests that Paxlovid's beneficial effects reducing hospitalization and mortality appear consistent regardless of the stage of CKD. This is reassuring, as it indicates that Paxlovid could be a viable therapeutic option for a wide range of kidney disease patients, regardless of how advanced their condition is.

The study also examined whether any subgroups of patients with specific comorbidities experienced different outcomes regarding CKD progression or eGFR decline after treatment with Paxlovid. "We saw very little evidence that any specific comorbidities had a meaningful impact on eGFR decline," Strohbehn said.

These findings are aligned with results from the EPIC-HR trial, which assessed the efficacy of Paxlovid in high-risk individuals with pre-existing immunity (from prior COVID-19 infection or vaccination). In a recent analysis of the EPIC-HR trial, we spoke with Pzifer. The researcher found that Paxlovid still provided significant benefits in preventing hospitalization and death in high-risk patients, even in the context of pre-existing immunity. Specifically, Paxlovid was shown to reduce the risk of hospitalization and death by 73.7% compared to a placebo. It also led to faster symptom resolution and reduced the incidence of severe symptoms.²

The similarities between these two studies are notable. Both highlight Paxlovid’s effectiveness in reducing severe COVID-19 outcomes in high-risk populations whether they are individuals with chronic kidney disease or those with pre-existing immunity from vaccination or prior infection. Both studies emphasize that Paxlovid is still beneficial for high-risk patients, though in the kidney disease study, it did not prevent CKD progression, unlike in the broader high-risk population examined in the EPIC-HR analysis.

As Strohbehn said, the exclusion of kidney disease patients from many clinical trials complicates the interpretation and application of clinical guidelines. "Since these patients were omitted from randomized trials, this study was our attempt to use observational data to assess treatment outcomes," he said. This highlights the ongoing need for research specifically targeting patients with advanced kidney disease, especially since they are among those most likely to suffer from severe COVID-19 outcomes.

Overall, both studies demonstrate the ongoing utility of Paxlovid in the management of COVID-19 in high-risk patients but also point to the necessity of personalized treatment strategies based on underlying health conditions such as kidney disease and pre-existing immunity. Strohbehn concluded, “We need more research to ensure that we can use Paxlovid safely and effectively in high-risk populations, particularly those with kidney disease, and to understand its long-term effects on kidney function.”

References

1. Strohbehn I, Ouyang T, Lee M, et al. The effect of nirmatrelvir-ritonavir on short- and long-term adverse outcomes from COVID-19 among patients with kidney disease: A propensity-score matched study, Open Forum Infectious Diseases, 2024; ofae756, https://doi.org/10.1093/ofid/ofae756

2. McLaughlin J, et. al. Efficacy of nirmatrelvir-ritonavir in high-risk trial participants with prior SARS-CoV-2 infection or vaccination: a pooled analysis Presentation #88 presented at IDWeek 2024. October 16-19, 2024. Los Angeles, CA.