Thread by @ben_geisler

#Paxlovid can reduce the risk of severe COVID.

Should we give to all "high risk" patients though - even if they're vaccinated +/- boosted ?

And does being in the BA.4/5 wave change anything?

#IDTwitter #MedTwitter #FOAMed
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Pax is one of the options for outpatients (ie, mild-moderate disease) with COVID to prevent severe disease (ie, O2/hospitalization or death)

Here's the best table I've seen, created by @RMKGandhi, as shown in a recent @IMJournalClub -

As you can see, Pax stacks up well in terms of
-the relative risk reduction (88%)
-the absolute risk reduction (-5.5%), and
-the inverse of the latter - number needed to treat (NNT, 18)

So in other words, you need to give Pax to 18 patients to prevent one case of severe disease

An NNT of 18 isn't bad compared to some other, well-accepted medical treatments:
-ABx for UGIB NNT=22 for mortality
-anti-HTN NNT=67 for 5yr-stroke prevention
-statins for known CAD NNT=83 for 5yr-mortality

Source: thennt.com

@WarrenChuang recently gave a whole @IMJournalClub on the EPIC-HR study - and dissected to it to the bone

EPIC-HR provided that NNT of 18 based on reducing risk from 6 to under 1%

HR in the study acronym stands for HIGH RISK (patients)

The key to understanding the study is to understands its inclusion criteria

nejm.org/doi/full/10.10…

EPIC-HR recruited n=2,246 patients according to the following criteria:
->18yrs
-confirmed symptomatic SARS-CoV2 Ix
-non-hospitalized (ie, mild-mod)
-UNVACCINATED
-at least 1 high risk for progression
-≥60yrs
-BMI>25
-smoker
-immunosup.
-chronic lung D/CVD/CKD/SCD/HTN/DM/Ca etc

Did you see that? They tested the study in the UNVACCINATED.

However, what seems to be happening is that we also give it to the VACCINATED if they have one or more risk factors for severe disease.

Does that make sense though? 🤓

@pfizer also did a yet unpublished study in standard risk patients: EPIC-SR (acronym checks out 😆)

SR here: low risk of hospitalization/death in the UNVACCINATED

Interim results/press release:
-relative risk reduction 71%
-the absolute risk reduction 2.4% - .7% = 1.7%
-NNT 59

However, there's another treatment that we use to prevent severe COVID

I'm of course talking about the vaccines

Vaccine effectiveness can be defined differently, but preventing hospitalization from Omicron is ~57% after six months and 90% after a booster, according the the CDC

Now these numbers might be slightly different with BA.4/5 (more on those variants in a minute), but let's play this out:

Baseline risk
-HR pts 6.3%
-SR pts 2.4%

>6mo after dose 2
-HR 2.7%
-SR 1%

Boosted
-HR 0.6%
-SR 0.2%

So if we assume the Pax has the same effect (RRR) on the vaccinated, we'd get

>6mo after dose 2
-HR: ARR 2.4%, NNT 42
-SR: ARR 0.8%, NTT 133

Boosted
-HR: ARR 0.5%, NNT 189
-SR: ARR 0.2%, NNT 667

Would you give or take Pax to patients who have had two shoots and are >6 months out?
To those with a booster?

I think the least sense makes SR patients with a booster

You could even argue that HR pts with a booster and SR patients with just 2 shots have NNTs that are too high

Keep also in mind the exorbitant costs of Pax, $530 per 5-day course - currently paid for by the U.S. government

@FiercePharma estimates around $24B revenue for Pax in 2022 alone

So on the economic dimension: is Pax for the vaccinated worth the money?

fiercepharma.com/pharma/pfizer-…

The other question is Pax rebound: becoming symptomatic/infectious again after initially testing negative

Rebound might occur if Pax levels aren't high enough (fast metabolizers) and/or if a 5d course is not long enough

Full disclosure: I am having one right now🤒😷

Why this is relevant:

Anecdotal data suggests that virus shedding may be longer with BA.4/5

So could see more than the 2-3% Pax patients having a rebound seen in the smaller studies that were conducted BEFORE BA.4/5 were the dominant variants

So Pax rebound is another potential reason why Pax in the vaccinated should be reconsidered in the BA.4/5 phase of the pandemic - rebound rates MAY be higher now and pts may be symptomatic and positive for a longer amount of time and hence to isolate and be out of work for longer

SUMMARY:
1⃣Giving Pax to UNVAX'ed pts w/ >1 symptom & mild-moderate to prevent severe disease is TOTALLY reasonable
2⃣Pax for UNVAX'ed pts w/ standard risk: MAY be reasonable, EPIC-SR results notwithstanding
3⃣Pax for BOOSTED w/ standard risk: UNREASONABLE

4⃣Everything else is a gray zone, but in the age of BA.4/5 Pax may not have much benefit (eg standard risk with 2+ doses or high risk with booster) and even prolong illness ("Pax rebound") for a few unlucky ones; also: high costs

/fin

P.S.: @Bob_Wachter and others seems to think risk of Pax rebound may be higher and mentions longer Pax studies are being planned/conducted

https://twitter.com/Bob_Wachter/status/1550165341313019904