Sullivan Joseph, Wirrell Elaine, Knupp Kelly G, Chen Dillon, Flamini Robert, Zafar Muhammad, Ventola Pam, Avendaño Javier, Wang Fei, Parkerson Kimberly A, Ticho Barry
University of California, San Francisco, CA, USA.
Mayo Clinic, Rochester, MN, USA.
Epilepsy Behav. 2024 Feb;151:109604. doi: 10.1016/j.yebeh.2023.109604. Epub 2024 Jan 13.
The BUTTERFLY observational study aims to elucidate the natural trajectory of Dravet syndrome (DS) and associated comorbidities in order to establish a baseline for clinical therapies. We present the 12-month interim analysis of the study.
Patients with a genetically confirmed diagnosis of DS were enrolled in the study. Adaptive functioning and neurodevelopmental status were measured using the Vineland Adaptive Behavior Scale, Third Edition (Vineland-III), Bayley Scales of Infant Development, Third Edition (BSID-III), and Wechsler Preschool and Primary Scale of Intelligence, Fourth Edition (WPPSI-IV). Executive function, ambulatory function and locomotor activities, and overall clinical status were measured using the Behavior Rating Inventory of Executive Function - Preschool Version (BRIEF-P) scale, Gillette Functional Assessment Questionnaire (Gillette FAQ), and Clinician or Caregiver Global Impression of Change scales (CGI-C or CaGI-C) respectively.
Overall, 36 patients were enrolled across three age groups, with 35 patients completing at least part or all of one post-baseline visit through Month 12. Significant improvements in receptive communication, as assessed by Vineland-III and BSID-III raw scores, and in verbal comprehension subtests, as assessed by WPPSI-IV raw scores, were observed in BUTTERFLY patients for the all-patient group. Many patients performed on the impaired end of the BRIEF-P Global Executive Composite scale at baseline suggesting difficulties in executive function, and no significant change was observed in BRIEF-P scores for the all-patient group. Most patients performed in the dynamic range of the Gillette FAQ at baseline, and no significant change was observed in Gillette FAQ scores for the all-patient group. Lastly, there was significant improvement observed in the CaGI-C scores for the all-patient group.
This BUTTERFLY interim analysis shows small improvements in communication skills along with stability in other developmental abilities across patients with DS enrolled in the study from baseline to Month 12.
BUTTERFLY观察性研究旨在阐明Dravet综合征（DS）的自然病程及相关合并症，以便为临床治疗建立基线。我们展示了该研究的12个月中期分析结果。
对基因确诊为DS的患者进行研究。使用文兰适应行为量表第三版（Vineland-III）、贝利婴幼儿发展量表第三版（BSID-III）以及韦氏学前和小学智力量表第四版（WPPSI-IV）来测量适应功能和神经发育状况。分别使用执行功能行为评定量表-学前版（BRIEF-P）、吉列特功能评估问卷（Gillette FAQ）以及临床医生或照顾者总体变化印象量表（CGI-C或CaGI-C）来测量执行功能、步行功能和运动活动以及总体临床状况。
总体而言，三个年龄组共纳入36例患者，其中35例患者在第12个月前至少完成了部分或全部基线后随访。在BUTTERFLY研究的所有患者组中，通过Vineland-III和BSID-III原始分数评估的接受性沟通能力以及通过WPPSI-IV原始分数评估的言语理解子测试均有显著改善。许多患者在基线时BRIEF-P总体执行综合量表处于受损范围，提示执行功能存在困难，且所有患者组的BRIEF-P分数未观察到显著变化。大多数患者在基线时处于Gillette FAQ的动态范围内，且所有患者组的Gillette FAQ分数未观察到显著变化。最后，所有患者组的CaGI-C分数有显著改善。
这项BUTTERFLY中期分析表明，在该研究中，从基线到第12个月，DS患者的沟通技能有小幅改善，其他发育能力保持稳定。
