1st Lequimbi Infusion..

frank2844, congrats and best of luck in your journey.

frank

I recently had my 35th infusion of Leqembi, I've also had zero side effects.

I was quite nervous for my first infusion, as I had never previously had an infusion. I recall an IV I once had for a prior illness, and it wasn't pleasant (I don't like needles). But after the initial prick from the needle insertion, you don't really feel anything at all. It's not like the Leqembi burns as it enters your body, or anything like that.

After my 1st infusion, I started to bring books to read, or my laptop computer to check e-mail, to relieve the boredom during the infusion. Perhaps the most boring part is after the infusion is complete, when they start the "observation period" to see if you have severe reactions to the infusion. The recommended time is something like 3 hours of observation after the initial infusion. This usually decreases with subsequent infusions. If you don't have any reactions, this period is sort of like watching paint dry - not a very exciting activity.

The question of "is the medication working" comes up often in this forum, and in other on-line forums. I have an Engineering background, so I like to use an analogy with a car. We own a Prius, and the onboard computer gives you a numerical score on how efficiently you operate the car between start/stop cycles in your journey. To get a lousy score, if you are the first car at a red light, you slam the gas pedal to the max as soon as the light turns green, then drive really fast to the next red light, where you slam on the brakes at the last moment to screech to a halt. If you want a great score, you very slowly accelerate when the light turns green (annoying all of the drivers behind you), and then slowly starting stopping way before you get to the red light (again annoying the people in a hurry to get somewhere, who want to drive as fast as possible for as long as possible in between lights).

In the Prius, it is easy to tell the difference between slamming the brakes when approaching a red light, versus very gently applying the brakes way before the red light. However, it is not so easy to tell the difference between moderate braking (say in the exact middle between these two extremes) and something between moderate breaking and very gentle braking. There is no indicator on the dashboard telling you the rate you are decelerating.

In a similar way, Alzheimer's is characterized by a very slow decline in cognitive functioning. Anti-amyloid medications (i.e. Leqembi & Kisunla) were shown to reduce the rate of cognitive decline in their respective clinical trials. Specifically, the average rate of cognitive decline for a big group of those on placebo was compared to the average rate of decline for those on Leqembi or Kisunla. This is the source of the numbers tossed around for reductions in cognitive decline (i.e. 27% slowing for Leqembi, 29% slowing for Kisunla, using the Clinical Dementia Rating - Sum of Boxes, or CDR-SB cognitive test, the only test used by both drug companies in their respective trials).

As a practical matter, how can any individual possibly determine that their cognitive decline is about 30% slower compared to what it would have been if they had not started on the drug? It seems to me that to accurately answer that question, I would need to be forecasting what my future cognitive capabilities would be if I weren't on Leqembi, and then compare that with my lived experience. I don't know how to do that.

When I relocated from OH to VA, my new Neurologist repeated the Montreal Cognitive Assessment (MoCA). I scored the same. This was 15 months after my first cognitive test, and after 10 months of being on Leqembi. This data is indicating that my cognition is unchaged, which I take as a very good thing. But the MoCA is a very quick and imprecise tool. It could probably detect large changes in cognition, but we are looking for very small changes in cognition over a short period. So again, while my MoCA test scores indicate I have not had any cognitive decline, my own gut feeling is that I have slipped a bit in cognition since starting on Leqembi.

As if this post isn't long enough, one more thought. Later analyses of small subgroups in both the Leqembi & Kisunla Phase 3 trial data by the respective companies has shown for those who start on the medication with no/low amounts of tau tangles (as measured by tau PET), significant fractions of the people showed zero cognitive decline (some even had cognitive improvement) during the trial. This seems to indicate that your performance with Kisunla/Leqembi may depend on how far your AD has advanced biologically, in terms of tau tangles. If you start on an anti-amyloid drug with low amounts of tau, you may have very good performance with the drug. But if you start with moderate or higher amounts of tau, the drug may not be as effective in slowing the cognitive decline. As most of us haven't had tau PET scans (I have not, they are mostly used today in clinical trials), this information isn't so helpful to us. But the data is hinting that your performance with an anti-amyloid drug may depend on how far the disease has advanced in your brain, in terms of tau tangles.