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Dr. Isaacson:
Welcome to a new episode of the Frontline of Alzheimer's Care, where we provide you with quick answers to burning questions from real clinicians about amyloid-targeting therapies in Alzheimer's disease.I'm Dr. Richard Isaacson, and I'm joined by doctors Gayatri Devi and Pierre Tariot, to help answer these questions. Let's hear from Dr. Chong.
Dr. Chong:
Once you selected a patient for monthly infusion amyloid-targeted therapy, I'm wondering how soon would you be expecting the side effects or the MRI changes to appear? And so, what's your regimen for monitoring patients? What are you actually looking for? And what do you ask the family to look out for? Are there behavioral changes? Is it more of a mental status or a level of consciousness change, etcetera?
Dr. Isaacson:
Dr. Devi, I look forward to your answer here because you know, we’ve been working on these sorts of approaches over the last couple of years together on several patients. And, you know, with your very individualized dosing schedule based on genetic risk and other factors I'm interested to hear how you track this.
Dr. Devi:
So I obviously tell patients and families to call me immediately if there's any issues with headaches, anything they're worried about, if there's any trouble at all with a focal deficit, whether it's a gait disorder, whether they're vomiting. But, you know, generally speaking, in our practice, we also very carefully do a thorough neurologic exam on all our patients once a month while they're in treatment to just see if they're having any difficulties. And ARIA, as a rule 74% of patients are asymptomatic with ARIA, and the symptomatic patients could have headaches, they could have confusion, they could have dizziness gait difficulties, etcetera. In my experience, of the four patients that we've had, who've had ARIA, two of them with microhemorrhages and the other two with significant brain edema there was never any symptoms nor were there signs on examination. These findings were picked up during their routine MRI evaluations.
And the question is, what do you do when you have a patient who has ARIA? And generally what I've done with all four patients, is given that they've been stable, given that there were no progression on MRI, I've opted to keep the patients on medications. And that's the general recommendation is if the person is symptomatic and they have mild symptoms, then you can decide whether or not to continue. If there's moderate symptoms, then you may want to suspend treatment, and then recheck the MRI, re-monitor the patient, and then decide on treatment. Alternatively, if a patient is asymptomatic, again, depending on what you see on the MRI, you may opt to continue treatment, or decide to stop treatment, take a pause, and then reevaluate. In our practice, because we're very, very careful with very close monitoring, as well as MRI follow-up we've been fortunate that we've not had to stop anybody who's been on treatment.
I will also say that we've had patients with ARIA significantly much later in the course of their treatment. So because of our slow titration, we had one patient who was on aducanumab, who's homozygous for the APOE4 allele, who developed significant ARIA edema 20 months after beginning treatment, but he's still being titrated up, so he's currently only on 7 mg/kg.
Dr. Isaacson:
Wow, that's eye-opening. And you know, when you bring FDA-approved drugs into clinical practice, and you allow clinicians to practice and the evidence-based yet safe and evidence-informed way that we do, that's the only way to learn these things. How is he doing now several weeks, several months after?
Dr. Devi:
He's stable. He's stable and he's back to being on medications. Back to being on the amyloid treatment, yes.
Dr. Isaacson:
Great. Dr. Tariot, there's a lot to cover there. What are some kind of high-level or more granular thoughts that you have?
Dr. Tariot:
Yeah, I have a couple of additional points. Just using donanemab as an example about 60% of ARIA-E occurred within 3 months. And that's sort of a rule of thumb that it’s more likely to occur earlier. But as you just heard from Dr. Devi, could occur quite late. The vast majority resolve without incident and treatment can be continued. In the case of donanemab, 6% of patients experienced recurrent ARIA-E.
And lastly, just recently presented was interesting data that elevated blood pressure or inadequate control of hypertension was strongly associated with the risk of ARIA-E. So that's one more thing to be extra careful about.
Dr. Isaacson:
So thank you, Dr. Chong, for bringing up this very important topic. For viewers interested in learning more, look at our other episodes about the ins and outs of amyloid-targeting therapies. Thank you all for listening.
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