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A Time-to-Event Exposure-Response Model for Amyloid-Related Imaging Abnormalities Following Administration of Aducanumab to Subjects With Early Alzheimer Disease
Muralidharan KK, Karumanchi S, Kowalski KG, Burkett P, Chapel S, Rajagovindan R, Nestorov I.. Journal of clinical pharmacology, 2022-04-04
Topic: Amyloid, tau and blood-test diagnosis
Amyloid-related imaging abnormalities with edema (ARIA-E) have been reported in patients with early Alzheimer disease treated with aducanumab. ARIA-E incidence has been observed to be dependent on both dose and apolipoprotein E4 carrier status. A time-to-event (TTE) approach applying data from 2 phase 3 studies (studies 301 and 302) was used to describe the effect of aducanumab serum exposure on the instantaneous risk of 2 end points: the first incidence of ARIA-E and time to ARIA-E resolution.
Key findings
- ARIA-E incidence has been observed to be dependent on both dose and apolipoprotein E4 carrier status.
- A time-to-event (TTE) approach applying data from 2 phase 3 studies (studies 301 and 302) was used to describe the effect of aducanumab serum exposure on the instantaneous risk of 2 end points: the first incidence of ARIA-E and time to ARIA-E resolution.
- A total of 3251 subjects with 826 events supported the TTE model to characterize the first ARIA-E event.
- The TTE resolution model was supported by data from 768 of 826 subjects who had ARIA-E resolved.
Why it matters
This modelling study used data from two phase 3 trials to describe how aducanumab serum exposure affects the risk of amyloid-related imaging abnormalities with edema (ARIA-E) and their resolution. It found that ARIA-E incidence depends on both dose and apolipoprotein E4 carrier status, which is a safety finding rather than evidence of clinical benefit.
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Study details
- Study designclinical trial
- Participants3,251
- Evidence strengthLow
How this study scored 35/100
Published in a peer-reviewed journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Journal of clinical pharmacology) |
| Journal's citation record | 2 / 4 | The Journal of Clinical Pharmacology: journal h-index 154 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | Design recorded as “clinical trial”, which our rubric does not rank (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 3 / 5 | 2022 — within 6 year(s) of the newest study here |
| Sample size | 3 / 4 | 3,251 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 1 / 7 | Cited 4 times (OpenAlex, 2026-10-10) |
| Citations per year | 0 / 5 | 0.7 citations a year over 6 year(s) since 2022 |
| Impact for its field and year | 1 / 6 | Cited 0.5× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 0 / 4 | Cited 1 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Ivan A. Nestorov: h-index 38 (OpenAlex, whole career) |
| Institution's track record | 0 / 3 | Biogen (United States): institution h-index 495 (OpenAlex) |
| Multi-centre collaboration | 0 / 3 | OpenAlex lists 1 institution(s) in 1 country — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 35285968) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 35 / 100 | — |
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Read the original
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Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record names 7 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
APA 7th
Muralidharan, K. K., Karumanchi, S., Kowalski, K. G., Burkett, P., Chapel, S., Rajagovindan, R., et al. (2022). A Time-to-Event Exposure-Response Model for Amyloid-Related Imaging Abnormalities Following Administration of Aducanumab to Subjects With Early Alzheimer Disease. Journal of clinical pharmacology. https://doi.org/10.1002/jcph.2047
Vancouver
Muralidharan KK, Karumanchi S, Kowalski KG, Burkett P, Chapel S, Rajagovindan R, et al. A Time-to-Event Exposure-Response Model for Amyloid-Related Imaging Abnormalities Following Administration of Aducanumab to Subjects With Early Alzheimer Disease. Journal of clinical pharmacology. 2022. doi:10.1002/jcph.2047. PMID: 35285968.
BibTeX
@article{muralidharan2022-35285968,
author = {Muralidharan, K. K. and Karumanchi, S. and Kowalski, K. G. and Burkett, P. and Chapel, S. and Rajagovindan, R. and Nestorov, I.},
title = {{A Time-to-Event Exposure-Response Model for Amyloid-Related Imaging Abnormalities Following Administration of Aducanumab to Subjects With Early Alzheimer Disease}},
journal = {Journal of clinical pharmacology},
year = {2022},
doi = {10.1002/jcph.2047},
pmid = {35285968},
url = {https://doi.org/10.1002/jcph.2047}
}
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