Patient Considerations When Prescribing Lecanemab for Alzheimer Disease

Following lecanemab-IRMB's (Leqembi™) full approval from the Food and Drug Administration (FDA) in July for treatment of early Alzheimer disease, eyes have turned to the groundbreaking world of Alzheimer disease research. Psych Congress Network met virtually with Paul Schulz, MD, a neurologist at the University of Texas Health Science Center, Houston, Texas, to learn about the crucial insights gained from studies on anti-amyloid therapies, find out why timing is everything, and discover the key inclusion and exclusion criteria that shape these cutting-edge trials. Dr Schulz also underscored the urgency of early detection and the ongoing quest for effective Alzheimer disease treatments.

Alzheimer disease research is on the brink of change, and Dr Schulz offers a unique perspective on the journey ahead.

Catch up on part 1: Advantages and Drawbacks of Lecanemab in Alzheimer Disease Treatment.

Or, jump to part 3: Lecanemab Considerations and Efficacy

Read the Transcript: 

Psych Congress Network: What should clinicians keep in mind when evaluating patients for potential treatment with this drug? Are there any patient characteristics or comorbidities that may affect the efficacy and safety profile?

Paul Schulz, MD: All of our studies of the anti-amyloid therapies initially enrolled people with a broad range of symptoms of Alzheimer's from very early disease to late in the disease. And what we found over the years are 2 very important facts. One is that the amyloid that we see in the brain of someone who comes in with even mild cognitive impairment has been accumulating for up to 20 years before they come in. What that means is that when we start treating someone, we're actually probably in the 21st or 22nd year. And what that means is 2 things. One is that it doesn't necessarily cure the disease but slows it down. And number 2, it means that only people who are very early in the disease process symptom-wise are helped by the therapies. It probably has to do with the fact that at year 1 when we meet someone, we're actually already in year 21.

But the point is that if their MMSC, for example, is above 22 out of 30, that's the group that tends to be benefited by all the anti-amyloid therapies, especially lecanemab, which we're talking about today. Once they slip below 22 and they're now about 23 to 25 years into the disease, the therapies just haven't worked at all. So criterion number 1, and most important, it's got to be real early in the disease that we see someone and get them evaluated and get them into therapy. Time is brain, so to speak. So it's really incumbent upon us as healthcare providers to try to educate the community to come in and see us when you have your very first symptom, don't wait a year or two, which is the actual average. Come and see us right away. And for us, the onus is to evaluate them as rapidly as we can and get them started on therapy because the later they are in the starting of it, the less well they do.

So in terms of inclusion, in all of the trials we have a certain age range that we include and for lecanemab it was 50 to 90, very broad range of ages. So 45 year old, you could give it, but the truth is we haven't given it to people before, so we don't know what'll happen or if they're 95. If they're 95, they usually progress very slowly and don't need it anyway. So two things then MMSC above 22 and age 50 to 90, those are the important inclusion criteria.

Exclusion criteria is a little different. That means who would you not want to give it to? As I mentioned, ARIA-H is one of the 3 big side effects of all these meds. So that means that we don't want to have someone on a blood thinner being given the medication because we don't want to take a chance on the disease process affecting the blood vessels, the antibody affecting the blood vessels, and then having a blood thinner present that might make things a lot worse. In the lecanemab trial, there were only 3 hemorrhages out of 900, and they were all 3 in people who were on major blood thinners like Pradaxa and Eliquis, real good blood thinners. Don't get me wrong, I'm not arguing against that. I'm just saying if you're on one of those, probably not a good idea to be in the trial.

And then the third person got TPA, which is of course the clock busting drug for stroke. So the warning there is that if one of the patients on one of our anti-amyloid therapies has a stroke and would benefit from TPA, we would encourage the neurologist giving it to think real carefully about risk benefit. Is this someone who's really going to benefit from TPA or are they kind of out of the window and probably not going to benefit, but get the potential hemorrhagic side effect. Remember to that about 2 to 7% of people given TPA a have a hemorrhage anyway from the TPA, and god forbid, one of our patients getting anti-amyloid therapy got TPA and had a hemorrhage. So those are the two conditions that we really want to stay away from if possible. Again, if you have a stroke and you need it, you need it. But the stroke therapy of TPA and getting major blood thinners. We should probably not give these medications to them.

Now, the other really big important point to make is that in our trials we take people with pretty much no other health problems, and that way we don't take a chance on making their health problems worse, and we don't take a chance on their health problem interfering with our ability to study a medication. It's hard enough to get a homogeneous group of people age 50 to 90 on all the things that they need to match on for the treated group and untreated group.

So the important point here is that a lot of diseases have not been seen in the patients that we've given the drugs to, and this is all of them because all of them have been in studies, and so we've avoided. So for example, we don't know what'll happen if we give it to someone with an autoimmune disorder. There's no reason that any of us can think of scientifically why it'd be a problem, but we've never done it. So if you have a person with autoimmune disorder, as an example, you'd probably want to have a long conversation about what we know and don't know and are we willing to undergo the risk of that. The same with heart disease, lung disease, liver disease, kidney disease, none of them were included in trials. So the honest truth scientifically is we don't know what would happen.

This is actually part of what we call phase 4 therapy, and that means we've gone through the 3 phases in people with clean medical histories, we've got a good result, low side effect profile. Now we go to phase 4, which is real world. That means all of the folks who have other diseases at the same time. And it's very important for all of us as we give these drugs in phase 4, meaning real world, that we report any potential side effects that we see. For example, I have a patient with a melanoma on the back of his knee. If I give him one of these drugs and it seems to get worse than the oncologist expects, I would report that so everybody else would be forewarned that maybe cancer and these drugs don't mix together.

The truth currently, as I mentioned those, we don't know. We don't know if these drugs will interfere with any of those diseases because we did not allow anybody with cancer, autoimmune disease, heart disease, et cetera, to be given the medications. 

Paul Schulz, MD, is a professor of neurology at McGovern Medical School at The University of Texas Health Science Center at Houston (UTHealth). He received his combined BA-MD degrees from Boston University in 1984. He did a medical internship there, and moved to Baylor College of Medicine for his residency in Neurology. He stayed for a laboratory fellowship in cellular neurophysiology after which he became an assistant professor. Later, he was an associate professor of neurology, neuroscience, and translational biology and molecular medicine. Dr. Schulz was also the vice chair of education for neurology, the deputy chair of the Methodist neurology service, and directed the Cognitive Disorders Clinics at Baylor and the Houston Veterans Administration Hospital.