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    Home > Active Ingredient News > Drugs Articles > AD therapy approved follow-up: Bojian releases more data; experts discuss how to use it

    AD therapy approved follow-up: Bojian releases more data; experts discuss how to use it

    • Last Update: 2021-07-30
    • Source: Internet
    • Author: User
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    At today's Alzheimer's Association International Conference (AAIC-2021), Biogen and Eisai announced the latest in their Alzheimer's disease antibody therapy Aduhelm (aducanumab) Data
    .
    At the same time, various groups of experts have published opinions on the use of this therapy in authoritative journals

    .
    In today's article, we will summarize this information and share it with readers and friends

    .

    What information has Bojian updated?

    In a Poster Presentation, the researchers analyzed the decrease in brain amyloid (Aβ) deposition caused by aducanumab, the changes in biomarkers of downstream Alzheimer's disease (AD) pathology, and the decline in clinical cognitive ability Slow down the relationship between
    .

    In the three clinical trials of PRIME, EMERGE, and ENGAGE, analysis at the population level showed that the reduction of Aβ deposition detected by PET scanning, and the relief of the decline in clinical symptoms detected by CDR-SB, were in different dose groups in different trials.
    There is a positive correlation (except for the high-dose group of the ENGAGE trial)

    .

    In addition, in the EMERGE clinical trial, a greater reduction in brain Aβ deposition is related to a greater reduction in tau protein and other neurodegeneration-related biomarkers in cerebrospinal fluid (CSF), and it is associated with a slower decline in clinical endpoints.
    Related

    .
    However, these correlations were not obvious in the ENGAGE test

    .

    The third analysis found that in the clinical trials of PRIME, EMERGE, and ENGAGE, patients whose brain Aβ deposition level fell below the threshold of negative amyloid test had a smaller decline in clinical endpoints
    .

    The press release pointed out that, taken together, these results are consistent with the hypothetical mechanism of action of aducanumab, and support that the changes in AD pathophysiological biomarkers stimulated by aducanumab are related to the remission of the decline in clinical endpoints
    .

    In other posters, further analysis of the EMERGE clinical trial showed that high-dose aducanumab treatment produced consistent effects on the predetermined indicators used to assess patients’ cognition, function, and behavior.
    This trial achieved both primary, secondary and Tertiary clinical endpoint

    .
    In 13 patient subgroups divided into 6 different factors such as ApoE ε4 status, baseline disease grade, etc.
    , aducanumab caused a dose-dependent decrease in Aβ deposition

    .
    The evaluation of amyloid-related imaging abnormalities (ARIA), the main side effect of antibody therapy, showed that 76% of patients treated with aducanumab showed no clinical symptoms in ARIA, and most ARIAs had mild or moderate radiological severity.
    And it is temporary

    .

    How is this therapy recommended?

    After aducanumab is approved by the US FDA for the treatment of AD, doctors need to know how to use this new treatment option appropriately
    .
    At the AAIC meeting, a group of 6 AD experts released their recommendations for the use of aducanumab

    .
    This recommendation was also published in The Journal of Prevention of Alzheimer's Disease

    .

    Suggestion 1: What kind of people can be treated?

    Since the key clinical trials of aducanumab are conducted in patients with early cognitive impairment or early AD dementia due to AD, and these patients have confirmed the presence of amyloid deposits in the brain through PET scans, the expert team recommends that the use of aducanumab should be limited In the same patient group where the efficacy and safety of this therapy have been studied
    .

    Recommendation 2: Starting dose and highest dose

    The recommendation of the expert group is that the starting dose of aducanumab should be 1 mg/kg, and then gradually increase until it reaches the target dose of 10 mg/kg
    .
    In the process of dose titration, the doctor should ask the patient whether there are any symptoms related to ARIA after each medication

    .

    ▲Dose titration recommendations for Aducanumab (picture source: reference [4])

    Recommendation 3: Potential risks and treatment

    The most common side effect of Aducanumab therapy is ARIA
    .
    In the high-dose treatment group, the incidence of ARIA was 35.
    2%, compared with 2.
    7% in the placebo group

    .
    It is more common in APOE ε4 allele carriers

    .
    The expert panel recommends MRI testing before starting treatment, during dose titration, and after receiving the highest dose of aducanumab infusion

    .
    If the patient has headaches, vomiting/nausea, dizziness and other symptoms that may indicate ARIA, MRI should be performed immediately

    .
    If ARIA causes clinical symptoms, or if the radiology of ARIA is moderate or severe, treatment should be suspended

    .
    If ARIA causes severe clinical symptoms (such as seizures, stroke, etc.
    ), treatment should be discontinued

    .



    ▲Risk assessment and treatment flowchart of aducanumab treatment (picture source: reference [4])

    Recommendation 4: When to terminate treatment

    In addition to the termination of treatment due to side effects, the expert panel also made recommendations for termination of treatment due to other reasons
    .
    Experts pointed out that the timing and strategy of stopping treatment have not been studied yet

    .
    The decision to stop treatment may be influenced by a variety of factors including ineffectiveness, inability to follow the treatment plan to receive treatment, and concerns about ARIA

    .

    It is worth mentioning that experts pointed out that aducanumab has not been tested in patients with moderate or severe AD, so if the early patients receive aducanumab treatment, the disease progresses to moderate dementia
    .
    Clinicians should carefully review the benefit/risk evidence of further treatment with the patient

    .

    What do the experts think about the recommendations for use?

    The Journal of Prevention of Alzheimer's Disease released comments from multiple groups of experts on this use suggestion at the same time
    .

    In terms of how to start treatment, two experts from McGill University said that the "recommendations for use" are based on the characteristics of the patients participating in the phase 3 clinical trial, which clearly defines which patients can receive treatment
    .
    At the same time, the "use recommendations" made special comments on patients with familial autosomal dominant AD and Down syndrome patients younger than 50 years old.
    These patient groups need independent randomized controlled trials to determine the effective dose and safety of aducanumab.
    Sexual characteristics

    .
    The recommendation to exclude patients "based on stroke evidence" requires more detail, because many early symptomatic AD patients have asymptomatic lacunar infarcts (lacunar infarcts) in non-strategic brain areas

    .

    Two experts from the University of Amsterdam Medical Center (Amsterdam UMC) said in the comments that it is not surprising that the "recommendations" recommended that aducanumab is suitable for use in the real world are the same as those participating in clinical trials of EMERGE and ENGAGE
    .

    Importantly, although the label of Aduhelm does not clearly state, the "recommendations for use" clearly state that patients suitable for Aduhelm treatment should be amyloid positive
    .
    This can be judged by an experienced scanning imaging doctor by using approved amyloid imaging reagents

    .
    Or have abnormal CSF biomarker levels

    .
    The reviewer emphasized that CSF's Aβ1-4 and p-tau 181 should both be abnormal in order to be judged as AD

    .

    In terms of when to stop treatment, two experts from McGill University said that "recommendations for use" have made some efforts to define when to stop treatment, including pointing out that ARIA causes severe clinical symptoms and cannot reach the therapeutic dose.
    And can not accept clinical and brain imaging monitoring and so on

    .
    But the author of "Recommendations for Use" did not clearly state that treatment should be stopped when patients reach moderate dementia

    .
    Insurance companies may need this standard.
    In the next batch of guidelines, moderate dementia may be defined as a CDR global score of 2, an MMSE score of less than 19 at least twice, and loss of daily life needs.
    Critical autonomy

    .

    Two experts from the Amsterdam University Medical Center (Amsterdam UMC) said that "use advice" gives important advice in monitoring ARIA
    .
    It should be emphasized that among clinical trial participants, 75% of ARIA had no clinical symptoms

    .
    In real-world practice, this ratio may be lower, because clinical trial participants are specifically asked about side effects

    .
    Nonetheless, the attending physician should be vigilant about side effects.
    If ARIA occurs, treatment should be suspended or the dosage of the drug should be reduced according to the "recommended use" standard

    .
    In the presence of severe clinical symptoms, the use of steroids is usually very effective

    .

    Two experts from McGill University added that these guidelines were given in the absence of peer-reviewed critical phase 3 clinical trial papers
    .
    Therefore, these recommendations may need to be revised when all the data is released

    .

    Impact on Alzheimer's disease research and development and care

    "Recommendations for use" pointed out that all patients considering the use of aducanumab need to understand that its expected benefit is to delay the rate of cognitive and functional decline, and it does not improve the patient's current clinical condition
    .

    The Journal of Prevention of Alzheimer's Disease released comments from a number of experts at the same time, discussing the impact of the approval of aducanumab on the development and care of Alzheimer's disease
    .

    In terms of research and development, the expert article pointed out that the approval of aducanumab will help change the public's impression of AD
    .
    Previously, many people felt that cognitive decline and dementia caused by aging could not be avoided, which may prevent patients and their families from seeking diagnosis and treatment

    .
    The authors hope that the attention from aducanumab's approval can help educate the public, encourage more patients to seek treatment, and allow more patients to participate in clinical trials

    .

    Another positive effect of Aducanumab's approval is that it may bring more investment in neurodegenerative disease research and further development of AD diagnostic methods
    .

    However, experts are also concerned that in the short term, the approval of aducanumab may make ongoing observational AD studies and randomized clinical trials more difficult
    .
    Because patients want to receive aducanumab treatment, they may withdraw from clinical trials, and the resources currently used for clinical research will be transferred to support the use of aducanumab

    .

    In the care of AD, experts pointed out that aducanumab is only a part of AD treatment and care
    .
    At present, most AD patients require comprehensive care, and professionals in this area are still very scarce

    .
    Aducanumab can only slow down the decline in clinical symptoms of AD in some patients, and it is not yet a curative treatment

    .
    Before innovative therapies that can change the course of the disease can be used by the majority of patients, it will play a key role in the public health strategy of AD, which includes the promotion of prevention, early detection and accurate diagnosis, comprehensive care, and support for nursing staff

    .

    Note: The original text has been deleted

    Reference materials:

    Reference materials:

    [1] Biogen and Eisai Announce ADUHELM™ (aducanumab-avwa) Data Presentations at Alzheimer's Association International Conference 2021.
    Retrieved July 27, 2021, from https:// Biogen and Eisai Announce ADUHELM™ (aducanumab-avwa) Data Presentations at Alzheimer's Association International Conference 2021.
    Retrieved July 27, 2021, from https:// [2] Biogen and Ionis report positive topline clinical data on investigational Alzheimer's disease treatment at AAIC.
    Retrieved July 27, 2021, from https://investors.
    biogen.
    com/news-releases/news-release-details/biogen-and- ionis-report-positive-topline-clinical-data

    [2] Biogen and Ionis report positive topline clinical data on investigational Alzheimer's disease treatment at AAIC.
    Retrieved July 27, 2021, from https://investors.
    biogen.
    com/news-releases/news-release-details/biogen-and- ionis-report-positive-topline-clinical-data

    [3] Gauthier and Rosa-Neto, (2021).
    The US Expert Panel on the Appropriate Use Recommendations of Aducanumab in Clinical Practice.
    The Journal of Prevention of Alzheimer's Disease, https://doi.
    org/10.
    14283/jpad.
    2021.
    44

    [3] Gauthier and Rosa-Neto, (2021).
    The US Expert Panel on the Appropriate Use Recommendations of Aducanumab in Clinical Practice.
    The Journal of Prevention of Alzheimer's Disease, https://doi.
    org/10.
    14283/jpad.
    2021.
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    [4] Cummings et al.
    , (2021).
    Aducanumab: Appropriate Use Recommendations.
    The Journal of Prevention of Alzheimer's Disease, https://doi.
    org/10.
    14283/jpad.
    2021.
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    [4] Cummings et al.
    , (2021).
    Aducanumab: Appropriate Use Recommendations.
    The Journal of Prevention of Alzheimer's Disease, https://doi.
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    [5] UNLV Alzheimer's Researcher and Expert Panel Present First-Use Recommendations For Aducanumab.
    Retrieved July 27, 2021, from https:// present-first-use-recommendations-for-aducanumab

    [5] UNLV Alzheimer's Researcher and Expert Panel Present First-Use Recommendations For Aducanumab.
    Retrieved July 27, 2021, from https:// present-first-use-recommendations-for-aducanumab

    [6] Weiner et al.
    , (2021).
    How Will Aducanumab Approval Impact AD Research? The Journal of Prevention of Alzheimer's Disease, https://doi.
    org/10.
    14283/jpad.
    2021.
    46

    [6] Weiner et al.
    , (2021).
    How Will Aducanumab Approval Impact AD Research? The Journal of Prevention of Alzheimer's Disease, https://doi.
    org/10.
    14283/jpad.
    2021.
    46

    [7] Kallmyer et al.
    , (2021).
    Impact of Aduhelm Approval on Care and Policy.
    The Journal of Prevention of Alzheimer's Disease, https://doi.
    org/10.
    14283/jpad.
    2021.
    42

    [7] Kallmyer et al.
    , (2021).
    Impact of Aduhelm Approval on Care and Policy.
    The Journal of Prevention of Alzheimer's Disease, https://doi.
    org/10.
    14283/jpad.
    2021.
    42
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