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Does Nirmatrelvir Work for Vaccinated Patients In the Omicron Era?

October 11, 2022

Written by Clay Smith

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Nirmatrelvir (Paxlovid) use in a population of largely immune outpatients ≥65 years old, during the omicron variant era, was significantly associated with reduction in hospitalization and death.

Why does this matter?
We know nirmatrelvir worked in high risk, unvaccinated patients in the delta variant era, but would it work in a largely vaccinated population during the omicron era?

Use the magic pill
This was a large health organization that covers half of the Israeli population. They found that nirmatrelvir was used infrequently in eligible patients, 3,902/109,254 (4%). This study was conducted during the omicron variant era (B.1.1.529), and 78% of the population had been vaccinated or had prior COVID-19 infection. Among eligible patients age ≥65 years who received nirmatrelvir vs those who did not, there was a significant reduction in hospitalization: 14.7 vs 58.0 per 100,000, aHR 0.27 (95%CI 0.15 to 0.49); or death: aHR 0.21 (95%CI 0.05 to 0.82). There was no significant difference in death or hospitalization in patients age 40-64, both around 15-16 per 100,000. What I take home is that omicron is already mild, but it can still be fatal, especially in older patients. Nirmatrelvir doesn’t have a lot of down side, and this suggests it’s best to use it in eligible patients, especially those ≥65.

Editor’s note: It bears mentioning that Pfizer ceased enrolment in their EPIC-SR (standard risk) trial due to lack of effect, which was much higher quality data on a population similar to this. ~Nick Zelt

Nirmatrelvir Use and Severe Covid-19 Outcomes during the Omicron Surge. N Engl J Med. 2022 Sep 1;387(9):790-798. doi: 10.1056/NEJMoa2204919. Epub 2022 Aug 24.

2 thoughts on “Does Nirmatrelvir Work for Vaccinated Patients In the Omicron Era?

  • Thank you for putting this together. I had the opposite take home from this study. The low rate of hospitalization and death tips the risk/benefit profile of this drug in this population quite steeply. I am calculating a NNT of >2300 (!) to prevent hospitalization. I would guess the NNH (adverse med reactions, rebound COVID etc) will be much lower than 2300. Am I missing something?


    • Yes, NNT = 2262 over age 65, which is not awesome. We knew the rate of hospitalization and death was already low in the omicron era. The drug pushes it even lower. But I hear what you’re saying – on a population basis, are we doing more good than harm? That’s a fair question. I’m not sure there is much harm. Does rebound COVID even matter, except for extended isolation? One thing is clear (and I should have emphasized this more), there is definitely room for shared decision making with our patients! ~Clay

What are your thoughts?