Academic Journal
Characterization of amyloid‐related imaging abnormality in the DIAN‐TU‐001 trial
| العنوان: | Characterization of amyloid‐related imaging abnormality in the DIAN‐TU‐001 trial |
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| المؤلفون: | Joseph‐Mathurin, Nelly, Llibre‐Guerra, Jorge J, McCullough, Austin A., Li, Yan, Hofmann, Carsten, Wojtowicz, Jakub, Wang, Qing, Wang, Guoqiao, Gordon, Brian A., Chen, Charles D., Brooks, William S., Gauthier, Serge, Holdridge, Karen C., Hsiung, Ging‐Yuek Robin, Jack, Clifford R., Klein, Gregory, Masellis, Mario, Mummery, Catherine J., Preboske, Gregory M., Santacruz, Anna, Wallon, David, Xiong, Chengjie, Yaari, Roy, McDade, Eric, Bateman, Randall J., Salloway, Stephen P., Benzinger, Tammie L.S., Clifford, David B. |
| المصدر: | Alzheimer's & Dementia ; volume 17, issue S1 ; ISSN 1552-5260 1552-5279 |
| بيانات النشر: | Wiley |
| سنة النشر: | 2021 |
| المجموعة: | Wiley Online Library (Open Access Articles via Crossref) |
| الوصف: | Background Amyloid‐related imaging abnormalities (ARIA), edema (E) or hemorrhagic (H) type, have been reported in trials of anti‐β‐amyloid passive immunotherapies in sporadic and dominantly inherited Alzheimer Disease (DIAD). However, beyond APOE‐ɛ4 the risk factors and clinical implications of ARIA are not well understood, especially in DIAD populations. Here we characterize ARIA, focusing on ARIA‐E in the DIAN‐TU‐001 trial evaluating gantenerumab and solanezumab in DIAD. Method The DIAN‐TU‐001 trial enrolled 194 participants, including 144 DIAD mutation‐carriers receiving gantenerumab (n=52), solanezumab (n=52), or a placebo (n=40). Clinical assessments included the Clinical Dementia Rating (CDR). Imaging assessments included PiB‐PET and safety MR, including T2‐FLAIR and T2*‐GRE. Treatment dosage and APOE‐ɛ4 status were also reported. Result Eleven participants developed a total of 14 ARIA‐E episodes (discovered on scheduled safety MR) and three had associated mild symptoms reported in retrospect ( e.g . headache, imbalance disorder). Though one ARIA‐E case was observed in the solanezumab arm, the following results focus on the gantenerumab arm to prevent unblinding. Recipients of gantenerumab were more likely to develop ARIA‐E compared to placebo (odds ratio (OR)=9.29, 95% confidence interval (CI)=[1.1,75.9], p ‐value<0.05). ARIA‐E participants were PiB‐PET+ and 60% were CDR>0. APOE‐ɛ4 tends to be associated with risk for developing ARIA‐E (OR=5.0, 95%CI=[1.0,30.4], p ‐value=0.055). ARIA‐E were not observed at initial 225mg dose and were first observed after a titration step (within 4‐24 weeks, after 1‐6 injections, Table 1). Time‐to‐resolution of ARIA‐E was 10.4±6.2weeks. Seven of ten ARIA‐E patients paused/reduced dose escalation and three discontinued treatment. Overall, developing ARIA‐E did not increase the odds of trial discontinuation (OR=1.57, 95%CI=[0.34,7.33], p ‐value=0.57). ARIA‐E occurred primarily in the occipital lobe (71%) with associated incident ARIA‐H (microhemorrhages or ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1002/alz.056393 |
| الاتاحة: | http://dx.doi.org/10.1002/alz.056393 https://onlinelibrary.wiley.com/doi/pdf/10.1002/alz.056393 https://onlinelibrary.wiley.com/doi/full-xml/10.1002/alz.056393 |
| Rights: | http://onlinelibrary.wiley.com/termsAndConditions#vor |
| رقم الانضمام: | edsbas.46512DAB |
| قاعدة البيانات: | BASE |
| DOI: | 10.1002/alz.056393 |
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