By Lucy Piper, medwireNews reporter
medwireNews: Appropriate use recommendations (AUR) for the anti-amyloid antibody donanemab in patients with Alzheimer’s disease (AD) have been made by the AD and Related Disorders Therapeutic Workgroup.
Gil Rabinovici (UCSF, San Francisco, California, USA), who presented the AUR at the 2024 Clinical Trials on Alzheimer’s Disease (CTAD) conference in Madrid, Spain, hopes that they will “guide clinicians in identifying appropriate treatment candidates in real-world practice.”
He pointed out that they are “recommendations, they are not guidelines or criteria, and as always when treating an individual patient, clinical judgment is paramount.”
The workgroup members devised the recommendations based on donanemab clinical trial data, FDA prescribing information, and other relevant literature alongside expert opinion.
They deemed a patient eligible for donanemab treatment to have mild cognitive impairment or mild dementia due to AD (Clinical Stages 3–4 on the Global Deterioration Scale) with a score between 20 and 30 on the Mini-Mental State Examination.
The patients should have evidence of amyloid-β pathology confirmed by either clinical read on positron emission tomography (PET) or cerebrospinal fluid (CSF) biomarkers, with amyloid-β 42/40 and phosphorylated (p)-tau181/amyloid-β42 ratios considered the most reliable.
Rabinovici commented that “the timing is not quite right” for blood-based biomarkers to be used to inform treatment eligibility, due to performance variability and the lack of experience with their use in clinical practice. However, he acknowledged that they “might be sufficient for treatment eligibility in the near future.”
Tau PET visual interpretation and quantification were used for patient inclusion in the initial TRAILBLAZER-ALZ 2 trial but given its limited access in clinical practice and the simplified binary read approved by the FDA for interpretation, the group recommends against its requirement, “but if it is available, it can be used to individualize estimate of clinical response,” said the presenter.
Conducting apolipoprotein E genotyping prior to treatment is recommended to advise patients on ARIA risk, as is magnetic resonance imaging (MRI) at 6–12 months beforehand to identify patients who might be at increased risk for adverse events and who should therefore be excluded.
These include people taking anticoagulants, who were not found to be at increased risk for ARIA in the TRAILBLAZER-ALZ 2 trial, said Rabinovici but “the data were limited,” and an increased risk for intracerebral hemorrhage with anticoagulation has been previously reported. He commented that this may change “as more data emerge from trials and real-world use,” and that there is no restriction on antiplatelet use.
Exclusion is also recommended for patients who have severe white matter disease or evidence of significant cerebral amyloid angiopathy on MRI, such as more than four microbleeds, any macrohemorrhage greater than 1 cm, and superficial siderosis.
To monitor treatment, follow-up MRI scans are recommended 1 month after the initial donanemab 700 mg dose prior to the second 700 mg infusion, and again before the third 700 mg infusion at month 3 and the 1400 mg infusion at month 4, and finally before the 7-month infusion.
Thrombolytics should not be used during donanemab treatment, although mechanical thrombectomy alone is considered feasible, said Rabinovici.
Discontinuation of donanemab is recommended if MRI identifies any macrohemorrhage, more than one area of superficial siderosis, more than 10 microhemorrhages, more than two episodes of ARIA, severe ARIA, or the patient requires treatment with an anticoagulant.
In addition, clinicians can consider discontinuing treatment typically at 12–18 months if the follow-up amyloid PET read is negative, noted Rabinovici.
He concluded that “to advance precision medicine in AD” there is a need for “FDA vetted and approved blood-based biomarkers for eligibility,” and “at least in select patients enhanced access and quantitative readouts for amyloid and tau PET,” and highlighted “the need for long-term real-world data on efficacy and safety.”
medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2024 Springer Healthcare Ltd, part of the Springer Nature Group
CTAD24; Madrid, Spain: Oct 29–Nov 1
