Helsingborg General Hospital, Dept. of Emergency Medicine and Prehospital Care, Helsingborg, Sweden; Lund University, Dept. of Clinical Sciences Lund, Clinical Sciences Helsingborg, Lund, Sweden.
Dept. of Clinical Chemistry and Pharmacology, Division of Laboratory Medicine, Lund, Sweden.
Epilepsy Behav. 2019 Jul;96:169-174. doi: 10.1016/j.yebeh.2019.04.029. Epub 2019 May 28.
Improved quality of life (QoL) is one of the most important objectives in the treatment of epilepsy. Recent prospective, clinical studies proved no significant differences between brand antiepileptic drugs (AEDs) and their generic equivalents in terms of seizure control, pharmacokinetics, or safety. In this study, we focused on possible changes in QoL and adverse events in connection with generic substitution of levetiracetam (LEV).
This was a prospective, naturalistic, two-cohort, twin-center study. After a baseline period of 10 weeks, outpatients with epilepsy on stable treatment with Keppra® either continued on this brand (reference group, n = 16) or switched to generic LEV (1A Pharma®) (study group, n = 16) for an eight-week study period. The Quality of Life in Epilepsy Inventory-31 (QOLIE-31) and an adverse events' questionnaire were administered at inclusion, after baseline, and at the end of the study period. The study protocol included a close clinical follow-up with repeated LEV serum concentration measurements and nurse-led outpatient visits.
Clinically relevant improvements in overall QOLIE-31 scores according to minimally important change (MIC) estimates were seen in both groups. QOLIE-31 subscales in both groups showed significantly less worry about seizures at the end of the study compared to scores at inclusion (study group: p = 0.01; reference group: p = 0.02). No significant deterioration in QoL or adverse events were observed following generic substitution. No switchbacks occurred.
We found reduced seizure worries over time among people with epilepsy allocated to either generic switch or continued treatment with brand LEV. We hypothesize that the nurse-led structured follow-up had an impact on seizure worries and switchback rates because of reduced nocebo effects. Further studies on generic AED substitution, focusing on psychological outcome measures, are warranted to test this supposition.
提高生活质量（QoL）是癫痫治疗的最重要目标之一。最近的前瞻性临床研究证明，在控制癫痫发作、药代动力学或安全性方面，品牌抗癫痫药物（AEDs）与仿制药之间没有显著差异。在这项研究中，我们专注于左乙拉西坦（LEV）仿制药替代可能引起的 QoL 变化和不良事件。
这是一项前瞻性、自然主义、双队列、双中心研究。在稳定使用开浦兰®治疗的癫痫门诊患者经过 10 周的基线期后，其中 16 例继续使用该品牌药物（参照组），另外 16 例患者换用仿制药（1A 制药®）（研究组）进行为期 8 周的研究。在纳入时、基线后和研究期末，使用癫痫生活质量问卷-31 （QOLIE-31）和不良事件问卷进行评估。该研究方案包括密切的临床随访、反复进行 LEV 血清浓度测量和护士主导的门诊随访。
根据最小重要变化（MIC）估计，两组的整体 QOLIE-31 评分均有临床相关改善。与纳入时的评分相比，两组的 QOLIE-31 子量表在研究期末的担忧发作情况明显减少（研究组：p=0.01；参照组：p=0.02）。仿制药替代后，QoL 或不良事件无明显恶化。未出现逆转。
我们发现，分配到仿制药转换或继续使用品牌 LEV 治疗的癫痫患者，随着时间的推移，担忧发作的情况有所减少。我们假设，由于减少了负面暗示的影响，护士主导的结构化随访对担忧发作和逆转率产生了影响。需要进一步开展关注心理结局测量的仿制药 AED 替代研究来验证这一假设。
