Department of Neurology, Johns Hopkins University, Baltimore, MD, USA.
IRCCS Mondino Foundation, Pavia, Italy.
Epilepsia. 2018 Apr;59(4):866-876. doi: 10.1111/epi.14044. Epub 2018 Mar 25.
To evaluate long-term safety/tolerability and seizure outcomes in patients with focal seizures treated with adjunctive perampanel in the open-label extension (OLEx) Study 307 (ClinicalTrials.gov identifier: NCT00735397).
Patients could enter the OLEx after completing one of the double-blind, phase III studies. Safety/tolerability and seizure outcomes (median percent reduction in seizure frequency per 28 days, and 50% responder and seizure freedom rates) were analyzed during the OLEx in cohorts with the same minimum perampanel exposure for all focal seizures and secondarily generalized seizures (SGS). An additional sensitivity analysis accounted for early dropouts from the OLEx.
Of 1480 patients randomized across the double-blind studies, 1218 enrolled in the OLEx. The majority of patients (65.4%-80.9%) received a last daily dose of perampanel 12 mg and completed long-term assessment on the same, or one fewer, concomitant antiepileptic drug compared with baseline. The long-term safety/tolerability profile was consistent with the double-blind studies. Treatment-emergent adverse events (TEAEs) leading to discontinuation in >1% of patients were dizziness, irritability, and fatigue; TEAEs of clinical interest were stable for 4 years. In all cohorts, seizure outcome improvements were sustained over time. Median percent seizure reductions per 28 days reached 62.0% and 70.6% for patients with ≥3 (n = 436) or ≥4 (n = 78) years of exposure, respectively; corresponding 50% responder rates were 59.6% and 67.9%. The largest median percent seizure reduction per 28 days occurred in SGS for patients with SGS at baseline: 88.0% and 100.0% for patients with ≥3 (n = 190) or ≥4 (n = 28) years of exposure, respectively; in these cohorts 40.0% and 53.6% of patients, respectively, attained freedom from SGS. Median percent seizure reductions per 28 days were similar when early dropouts were accounted for.
Long-term (≤4 years) adjunctive perampanel treatment did not raise new safety/tolerability signals and was associated with markedly improved seizure control, particularly in patients with SGS at baseline.
评估在开放标签扩展（OLEx）研究 307 中接受附加性吡仑帕奈治疗的局灶性发作患者的长期安全性/耐受性和癫痫发作结局（ClinicalTrials.gov 标识符：NCT00735397）。
在完成一项双盲、III 期研究后，患者可进入 OLEx。在 OLEx 中，根据所有局灶性发作和继发性全面性发作（SGS）的相同最低吡仑帕奈暴露时间，对各队列进行安全性/耐受性和癫痫发作结局（每 28 天的发作频率中位数降低百分比，以及 50%反应率和无发作率）分析。一项额外的敏感性分析考虑了 OLEx 的早期脱落。
在双盲研究中，1480 名随机患者中，有 1218 名患者入组 OLEx。大多数患者（65.4%-80.9%）接受了最后一次每日剂量 12 毫克吡仑帕奈治疗，并与基线相比，完成了长期评估，使用的相同或更少的一种伴随抗癫痫药物。长期安全性/耐受性与双盲研究一致。导致 1%以上患者停药的治疗中出现的不良事件（TEAE）是头晕、易怒和疲劳；4 年内，具有临床意义的 TEAEs 稳定。在所有队列中，癫痫发作结局的改善均随时间持续。每 28 天的发作频率中位数降低百分比分别达到 62.0%和 70.6%，分别为暴露时间≥3 年（n = 436）或≥4 年（n = 78）的患者；相应的 50%反应率分别为 59.6%和 67.9%。对于基线时有 SGS 的患者，SGS 中每 28 天的最大中位发作减少百分比分别为：暴露时间≥3 年（n = 190）或≥4 年（n = 28）的患者为 88.0%和 100.0%；在这些队列中，分别有 40.0%和 53.6%的患者无 SGS。当考虑早期脱落时，每 28 天的发作频率中位数降低百分比相似。
长期（≤4 年）附加性吡仑帕奈治疗不会产生新的安全性/耐受性信号，与明显改善的癫痫控制相关，尤其是基线时有 SGS 的患者。
