PT -期刊文章盟Florian Deisenhammer盟土地肥沃的闪避AU -安娜劳伦盟安德斯Sjodin AU -马林Ryner盟安娜Fogdell-Hahn盟——克劳迪娅·西弗斯盟Raija林德伯格AU -保罗•埃里克·延森盟路易Christodoulou AU -玛丽Birchler AU -迈克尔·奥尔AU - Marc Pallardy TI -预测长期持续性Natalizumab禁毒抗体(P5.404) DP - 2017年4月18日TA -神经病学PG - P5.404 VI - 88 IP - 16补充4099 - //www.ez-admanager.com/content/88/16_Supplement/P5.404.short 4100 - //www.ez-admanager.com/content/88/16_Supplement/P5.404首页.full所以Neurology2017 4月18日;88 AB -目的:预测长期持续性Natalizumab禁毒(ADA)的抗体。背景:Natalizumab-ADA发展早期的治疗期间,与失去功效。连续治疗患者应该停止2 ADA积极成果是由当前基于ELISA试验,只有报告定性(正/负)但没有滴度。没有什么是知道的大小Natalizumab-ADA响应和长期持续。设计/方法:在ABIRISK项目(www.abirisk.eu),致力于探索ADA对多种药物,我们开发了一个高度敏感的Natalizumab ADA基于中尺度分析发现(MSD)平台,和PK试验测量药物水平。我们包括46名患者积极ELISA-ADA结果在3个月的治疗起始(基线)的后续治疗血清样本可用10 - 24个月后开始,无论后续治疗。MSD-ADA和药物含量测量基线和随访的样本。结果:治疗基线平均时间是2个月,在随访19个月。在基线中ADA效价是4603和302在随访。 There was a strong correlation (R=0.64) between baseline and follow-up titres. A complete reversion to ADA negativity occurred in 10 patients, all still on treatment with detectable drug levels (mean 10.8 μg/mL). Of 36 patients with persisting ADA, 10 were still on treatment with detectable drug levels in 3 patients (cutoff 0.17 μg/mL). The latter had a mean ADA titer of 15 (very low). Continuous Natalizumab treatment had no influence on ADA titer change. A baseline titer of >800 predicted ADA persistency with 89% sensitivity and 90% specificity (likelihood ratio 8.9).Conclusions: Although ADA titers decline over time, high baseline Natalizumab-ADA titers accurately predict persistency. Despite continuous treatment, the majority of patients with persistent ADA had no detectable drug levels indicating loss of efficacy in line with phase 3 study results.Study Supported by: Public funding by European Union, Innovative Medicine Initiative (IMI), Grant Agreement No. 115303Disclosure: Dr. Deisenhammer has received personal compensation for activities with Biogen, Sanofi Genzyme, Merck, and Novartis. Dr. Deisenhammer has received research support from Biogen. Dr. Jank has nothing to disclose. Dr. Lauren has received personal compensation for activities with Eurodiagnostica as an employee. Dr. Sjodin has received personal compensation for activities with Eurodiagnostica as an employee. Ms. Lundkvist has received research support from Biogen Idec. Dr. Fogdell-Hahn has received personal support from Biogen Idec. Dr. Sievers has nothing to disclose. Dr. Lindberg has nothing to disclose. Dr. Jensen has nothing to disclose. Dr. Christodoulou has received personal compensation for activities with UCB Celltech as an employee. Dr. Birchler has received personal compensation for activities with GlaxoSmithKline as an employee. Dr. Auer has nothing to disclose. Dr. Pallardy has nothing to disclose.