What are the considerations for restarting lequembi (donanemab) after discontinuation due to amyloid reversal in a patient with Alzheimer's disease?

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From the FDA Drug Label

LEQEMBI can cause amyloid related imaging abnormalities -edema (ARIA-E) and -hemosiderin deposition (ARIA-H) [see Warnings and Precautions (5. 1)]. Resumption of dosing should be guided by clinical judgment. ARIA-E The recommendations for dosing interruptions for patients with ARIA-E are provided in Table 1 Suspend until MRI demonstrates radiographic resolution and symptoms, if present, resolve; consider a follow-up MRI to assess for resolution 2 to 4 months after initial identification.

The decision to restart lequembi after it has been stopped due to amyloid reversal should be guided by clinical judgment.

  • The patient should be monitored for ARIA (amyloid-related imaging abnormalities) using MRI scans.
  • Dosing interruptions for patients with ARIA-E are provided in Table 1 of the drug label.
  • Resumption of dosing should occur when MRI demonstrates radiographic resolution and symptoms have resolved.
  • A follow-up MRI should be considered to assess for resolution 2 to 4 months after initial identification 1.

From the Research

Restarting Leqembi (donanemab) after discontinuation due to amyloid reversal should be considered on a case-by-case basis, with careful monitoring and comprehensive safety screening, as the long-term management following amyloid clearance remains an evolving area of clinical practice. The decision to restart therapy should involve shared decision-making between the clinician, patient, and caregivers, weighing potential benefits against risks of adverse effects. Patients should undergo regular monitoring with amyloid PET scans or CSF biomarkers to assess for potential re-accumulation of amyloid plaques, typically every 6-12 months after discontinuation. If significant amyloid reaccumulation is detected (approaching or exceeding the initial treatment threshold), restarting donanemab may be considered. The standard dosing regimen would likely be resumed (donanemab 700 mg IV every four weeks) 2. Before restarting, patients should undergo comprehensive safety screening, including MRI to rule out ARIA (Amyloid-Related Imaging Abnormalities), genetic testing for APOE ε4 status to assess ARIA risk, and careful evaluation of cognitive function to document any changes since discontinuation.

Some key considerations for restarting donanemab include:

  • The potential for amyloid reaccumulation over time, which may necessitate periodic retreatment to maintain clinical benefits 3
  • The risk of adverse effects, such as amyloid-related imaging abnormalities (ARIAs), which must be carefully monitored and managed 4
  • The importance of comprehensive safety screening, including MRI and genetic testing, to assess the risk of ARIAs and other potential adverse effects 2
  • The need for shared decision-making between the clinician, patient, and caregivers, weighing potential benefits against risks of adverse effects 2

It is essential to note that the current evidence base for restarting donanemab after discontinuation due to amyloid reversal is limited, and further research is needed to fully understand the long-term effects of this treatment approach 5, 6. However, based on the available evidence, a careful and individualized approach to restarting donanemab, with close monitoring and comprehensive safety screening, is recommended.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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