Amyloid-Related Imaging Abnormalities in the DIAN-TU-001 Trial of Gantenerumab and Solanezumab: Lessons from a Trial in Dominantly Inherited Alzheimer Disease.
Amyloid-Related Imaging Abnormalities in the DIAN-TU-001 Trial of Gantenerumab and Solanezumab: Lessons from a Trial in Dominantly Inherited Alzheimer Disease.
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DOI：
10.1002/ana.26511
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发表时间：
2022-11
影响因子：
11.2
通讯作者：
Clifford, David B.
中科院分区：
文献类型：
--
作者：
Joseph-Mathurin, Nelly;Llibre-Guerra, Jorge J.;Li, Yan;McCullough, Austin A.;Hofmann, Carsten;Wojtowicz, Jakub;Park, Ethan;Wang, Guoqiao;Preboske, Gregory M.;Wang, Qing;Gordon, Brian A.;Chen, Charles D.;Flores, Shaney;Aggarwal, Neelum T.;Berman, Sarah B.;Bird, Thomas D.;Black, Sandra E.;Borowski, Bret;Brooks, William S.;Chhatwal, Jasmeer P.;Clarnette, Roger;Cruchaga, Carlos;Fagan, Anne M.;Farlow, Martin;Fox, Nick C.;Gauthier, Serge;Hassenstab, Jason;Hobbs, Diana A.;Holdridge, Karen C.;Honig, Lawrence S.;Hornbeck, Russ C.;Hsiung, Ging-Yuek R.;Jack, Clifford R.;Jimenez-Velazquez, Ivonne Z.;Jucker, Mathias;Klein, Gregory;Levin, Johannes;Mancini, Michele;Masellis, Mario;McKay, Nicole S.;Mummery, Catherine J.;Ringman, John M.;Shimada, Hiroyuki;Snider, B. Joy;Suzuki, Kazushi;Wallon, David;Xiong, Chengjie;Yaari, Roy;McDade, Eric;Perrin, Richard J.;Bateman, Randall J.;Salloway, Stephen P.;Benzinger, Tammie L. S.;Clifford, David B.
确定gantenerumab或solanezumab治疗显性遗传性阿尔茨海默病（DIAD）试验中淀粉样蛋白相关成像异常（ARIA）受试者的特征。142例DIAD突变携带者接受了gantenerumab SC（n = 52）、solanezumab IV（n = 50）或安慰剂（n = 40）治疗。参与者接受了临床痴呆评级®（CDR®）、神经心理学测试、CSF生物标志物、β淀粉样蛋白正电子发射断层扫描（PET）和磁共振成像（MRI）评估，以监测ARIA。横断面和纵向分析评价了潜在的ARIA相关风险因素。11名参与者出现ARIA‐E，其中3名症状轻微。solanezumab组未报告ARIA-E，而与安慰剂组相比，gantenerumab组与ARIA-E相关（比值比[OR] = 9.1，置信区间[CI][1.2，412.3]; p = 0.021）。在gantenerumab治疗下，APOE-β 4携带者更有可能发生ARIA-E（OR = 5.0，CI[1.0，30.4]; p = 0.055），基线时有微出血的个体也是如此（OR = 13.7，CI[1.2，163.2]; p = 0.039）。在最初的225 mg/月gantenerumab剂量下未观察到ARIA-E，大多数病例在>675 mg剂量下观察到。在首次发生ARIA‐E时，所有ARIA‐E参与者均为淀粉样蛋白‐PET+，60%的CDR >0，60%超过了症状发作的估计年份，60%还发生了ARIA‐H。大多数ARIA‐E在剂量调整后影像学消退，并且发生ARIA‐E并未显著增加试验中止的几率。ARIA‐E更常见于枕叶（90%）。ARIA-E严重程度与ARIA-E发生时的年龄相关。在DIAD中，solanezumab与ARIA无关。Gantenerumab剂量超过225 mg会增加ARIA‐E风险，APOE‐ E4（+）个体或微出血的风险增加。在大多数情况下，ARIA‐E在MRI上是可逆的，通常无症状，没有额外的试验中止风险。神经网络2022;92：729-744
To determine the characteristics of participants with amyloid‐related imaging abnormalities (ARIA) in a trial of gantenerumab or solanezumab in dominantly inherited Alzheimer disease (DIAD). 142 DIAD mutation carriers received either gantenerumab SC (n = 52), solanezumab IV (n = 50), or placebo (n = 40). Participants underwent assessments with the Clinical Dementia Rating® (CDR®), neuropsychological testing, CSF biomarkers, β‐amyloid positron emission tomography (PET), and magnetic resonance imaging (MRI) to monitor ARIA. Cross‐sectional and longitudinal analyses evaluated potential ARIA‐related risk factors. Eleven participants developed ARIA‐E, including 3 with mild symptoms. No ARIA‐E was reported under solanezumab while gantenerumab was associated with ARIA‐E compared to placebo (odds ratio [OR] = 9.1, confidence interval [CI][1.2, 412.3]; p = 0.021). Under gantenerumab, APOE‐ɛ4 carriers were more likely to develop ARIA‐E (OR = 5.0, CI[1.0, 30.4]; p = 0.055), as were individuals with microhemorrhage at baseline (OR = 13.7, CI[1.2, 163.2]; p = 0.039). No ARIA‐E was observed at the initial 225 mg/month gantenerumab dose, and most cases were observed at doses >675 mg. At first ARIA‐E occurrence, all ARIA‐E participants were amyloid‐PET+, 60% were CDR >0, 60% were past their estimated year to symptom onset, and 60% had also incident ARIA‐H. Most ARIA‐E radiologically resolved after dose adjustment and developing ARIA‐E did not significantly increase odds of trial discontinuation. ARIA‐E was more frequently observed in the occipital lobe (90%). ARIA‐E severity was associated with age at time of ARIA‐E. In DIAD, solanezumab was not associated with ARIA. Gantenerumab dose over 225 mg increased ARIA‐E risk, with additional risk for individuals APOE‐ɛ4(+) or with microhemorrhage. ARIA‐E was reversible on MRI in most cases, generally asymptomatic, without additional risk for trial discontinuation. ANN NEUROL 2022;92:729–744
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DOI：
10.1016/j.dadm.2016.02.006
发表时间：
2016
期刊：
Alzheimer's & dementia (Amsterdam, Netherlands)
影响因子：
--
作者：
Siemers E;Holdridge KC;Sundell KL;Liu-Seifert H
通讯作者：
Liu-Seifert H
影响因子：
82.9
作者：
Salloway S;Farlow M;McDade E;Clifford DB;Wang G;Llibre-Guerra JJ;Hitchcock JM;Mills SL;Santacruz AM;Aschenbrenner AJ;Hassenstab J;Benzinger TLS;Gordon BA;Fagan AM;Coalier KA;Cruchaga C;Goate AA;Perrin RJ;Xiong C;Li Y;Morris JC;Snider BJ;Mummery C;Surti GM;Hannequin D;Wallon D;Berman SB;Lah JJ;Jimenez-Velazquez IZ;Roberson ED;van Dyck CH;Honig LS;Sánchez-Valle R;Brooks WS;Gauthier S;Galasko DR;Masters CL;Brosch JR;Hsiung GR;Jayadev S;Formaglio M;Masellis M;Clarnette R;Pariente J;Dubois B;Pasquier F;Jack CR Jr;Koeppe R;Snyder PJ;Aisen PS;Thomas RG;Berry SM;Wendelberger BA;Andersen SW;Holdridge KC;Mintun MA;Yaari R;Sims JR;Baudler M;Delmar P;Doody RS;Fontoura P;Giacobino C;Kerchner GA;Bateman RJ;Dominantly Inherited Alzheimer Network–Trials Unit
通讯作者：
Dominantly Inherited Alzheimer Network–Trials Unit
DOI：
10.1186/s13195-017-0318-y
发表时间：
2017-12-08
期刊：
Alzheimer's research & therapy
影响因子：
--
作者：
Ostrowitzki S;Lasser RA;Dorflinger E;Scheltens P;Barkhof F;Nikolcheva T;Ashford E;Retout S;Hofmann C;Delmar P;Klein G;Andjelkovic M;Dubois B;Boada M;Blennow K;Santarelli L;Fontoura P;SCarlet RoAD Investigators
通讯作者：
SCarlet RoAD Investigators
影响因子：
9
作者：
Klein, Gregory;Delmar, Paul;Doody, Rachelle
通讯作者：
Doody, Rachelle
影响因子：
5.7
作者：
Su Y;Blazey TM;Snyder AZ;Raichle ME;Marcus DS;Ances BM;Bateman RJ;Cairns NJ;Aldea P;Cash L;Christensen JJ;Friedrichsen K;Hornbeck RC;Farrar AM;Owen CJ;Mayeux R;Brickman AM;Klunk W;Price JC;Thompson PM;Ghetti B;Saykin AJ;Sperling RA;Johnson KA;Schofield PR;Buckles V;Morris JC;Benzinger TLS;Dominantly Inherited Alzheimer Network
通讯作者：
Dominantly Inherited Alzheimer Network