The always interesting stats are those which come from medication-naive people, i.e. people who know nothing about a given medication rather than from those who already have preconceived ideas for or against, that way one avoids placebo/nocebo effects to a greater degree.
In that spirit, I read two studies involving rapamycin and presumably rapamycin-naive patients. The interesting part is not the effect of rapamycin for the indication, i.e. the effect for the disease, but rather how people reacted to rapamycin quite APART from what it did or did not do for their disease. Study one:
Again, the disease and the effect of rapamycin on the disease is not what’s interesting here. Rather it is this quote:
“Three patients discontinued rapamycin for less than 1-month due to intolerance to adverse events, then, 12 patients received ≥1 dose of the rapamycin and provided ≥1 post-baseline target score after baseline were included for intent-to-treat (ITT) analysis. 100% (5/5) of patients with upper gastrointestinal strictures achieved clinical response after using rapamycin. However, no clinical response was observed in those patients with CD lesions in lower gastrointestinal tract. Adverse events occurred in 40% (6/15) of patients. No death or serious opportunistic infections were observed in the present study.”
Now, this is a small study, but it is in patients who had presumably no preconceived ideas about rapamycin one way or another - yet, right off the bat 20% had to drop out because of how bad the side effects were, and the overall rate of adverse events was 40%. That’s a very high rate for an FDA cleared drug, clearly we’re not dealing with aspirin here. However, on the plus side, there were no serious opportunistic infections - but again, this was a small study (15 subjects).
Second:
Quote:
“Despite a median sirolimus therapy duration of 524 days and some therapeutic benefits, all patients discontinued therapy due to adverse effects. Our findings suggest that while sirolimus may have clinical utility, its role may be limited by treatment-derived adverse effects.”
OK, this is smaller yet, and in pretty sick patients. It’s only 4 subjects. However, what is interesting is that again, all were presumably rapamycin naive, and yet all 4 stopped the drug due to adverse effects - a 100% quit rate due to adverse side effects despite deriving benefits from the drug vs their disease. And this was in subjects who didn’t quit immediately, but gave it a long, long try - well over a year, a fair chance for a drug by any standard. The conclusion the authors reach is pretty devastating: even though rapamycin may be an effective drug, the adverse effects are so bad, that they seriously undermine the use case for this drug.
The point here is that we can’t appeal to people’s imaginations, placebo or nocebo. People take the drug, and it has its effects and there seems to be a very large rate of events adverse enough that the quit rate is very high regardless of benefits.
So when people report not doing well on rapamycin, it is well worth taking them seriously, rather than chalking it up to prejudice or primarily psychosomatic reactions.
I still intend to take rapa in the next few months, but I am under no illusion that this is necessarily going to be smooth sailing, akin to popping a tylenol. We’ll see. YMMV.
