Nirmatrelvir/ritonavir rarely leads to rebound, doesn't help average-risk patients, studies find

A retrospective analysis found that symptom rebound occurred in less than 1% of high-risk COVID-19 patients treated with nirmatrelvir/ritonavir, while the manufacturer reported that the drug didn't show significant benefit in average-risk patients.

The COVID-19 pill nirmatrelvir/ritonavir (Paxlovid) was the focus of research last week.

A retrospective study, published by Clinical Infectious Diseases on June 14, looked at high-risk patients from one health system to analyze the phenomenon of COVID-19 symptom rebound after nirmatrelvir/ritonavir treatment. It included 483 patients, with a median age of 63 years; 93% were fully vaccinated. The average time from a positive test to prescription of nirmatrelvir/ritonavir was one day. Four patients (0.8%), all fully vaccinated, experienced rebound, at a median of nine days (interquartile range, 7 to 14.5 days) after treatment. None of the patients required hospitalization. In the full study population, two patients (0.4%) were hospitalized for reasons unrelated to rebound; both required ICU care but survived.

The authors concluded that the rebound phenomenon was uncommon in their high-risk population and that overall, patients treated with nirmatrelvir/ritonavir had favorable outcomes. “Extending the duration of NM/R [nirmatrelvir/ritonavir] treatment to prevent this rebound phenomenon has been suggested. However, our data suggests that this may not be necessary,” they wrote. The study wasn't large enough to identify risk factors for rebound “but it is notable that the four patients with rebound had multiple underlying medical comorbidities and had received SARS-CoV-2 vaccine more than 90 days prior to NM/R therapy,” the authors said.

Pfizer, the manufacturer of nirmatrelvir/ritonavir, released new data on the drug in a press release. According to interim trial results, patients at standard risk for severe COVID-19 who took nirmatrelvir/ritonavir had a nonsignificant 51% relative risk reduction in the primary endpoint of self-reported, sustained alleviation of all symptoms for four consecutive days. Due to the “very low rate of hospitalization or death observed in the standard-risk patient population,” the company decided to stop enrollment of average-risk patients and focus on use of the drug in more vulnerable populations, the press release said.

Other recent COVID-19 research looked at postacute sequelae and vaccine uptake. A Dutch study, published by the American Journal of Respiratory and Critical Care Medicine on June 13, found that severe obesity was associated with long-term symptoms in patients who had been treated in the ICU for COVID-19. The cause of this association is unknown, but it suggests “that long-term follow-up is of explicit importance in obese COVID-19 ICU patients,” the study authors said.

A letter published by the New England Journal of Medicine on June 15 compared COVID-19 and flu vaccination rates across states and found that low uptake of the COVID-19 vaccines was associated with reductions in flu vaccination. Finally, on June 17, the FDA authorized emergency use of the Moderna and Pfizer-BioNTech COVID-19 vaccine in children down to six months of age, and the CDC recommended the vaccines for this age group on June 18.