Carreño Mar, Benbadis Selim, Rocha Francisco, Blum David, Cheng Hailong
Epilepsy Unit Hospital Clinic Barcelona Spain.
Department of Neurology University of South Florida Tampa Florida U.S.A.
Epilepsia Open. 2017 Nov 9;2(4):459-466. doi: 10.1002/epi4.12083. eCollection 2017 Dec.
To investigate whether adjunctive eslicarbazepine acetate (ESL) could lead to exacerbation of seizures in some patients.
Post-hoc analysis of data pooled from three Phase III trials of adjunctive ESL (studies 301, 302, and 304) for refractory partial-onset seizures (POS). Following an 8-week baseline period, patients were randomized to receive placebo or ESL 400, 800, or 1,200 mg once daily (2-week titration, 12-week maintenance, 2-4 week tapering-off periods). Patient seizure diary data and seizure treatment-emergent adverse event (TEAE) reports were pooled for analysis.
The modified intent-to-treat and safety populations comprised 1,410 patients and 1,447 patients, respectively. : Compared with placebo (32/21%), significantly smaller proportions of patients taking ESL 800 mg (20/15%) and 1,200 mg (22/12%) had a ≥25/≥50% increase in standardized seizure frequency (SSF) from baseline; there was no significant difference between placebo and ESL 400 mg. : Compared with placebo (20%), significantly smaller proportions of patients taking ESL (400 mg, 12%; 800 mg, 12%; 1,200 mg, 14%) had an increase in SSF ≥25%. When evaluating ≥50% increases in SSF, only ESL 800 mg (7%) was significantly different from placebo (12%). Some patients had no secondarily generalized tonic-clonic (sGTC) seizures during baseline but had ≥1 sGTC seizure during maintenance treatment (placebo, 11%; ESL 400 mg, 5%; 800 mg, 10%; 1,200 mg, 5%). Fewer patients had a ≥25% increase in sGTC seizure frequency with ESL (400 mg, 11%; 800 mg, 9%; 1,200 mg, 14%) versus placebo (19%). The incidence of seizures reported as TEAEs was low in all treatment groups; incidences were generally lower with ESL versus placebo. : Similar proportions of patients taking ESL and placebo had a ≥25/≥50% increase in SSF. Seizure TEAE incidence was numerically higher with ESL versus placebo.
Treatment with adjunctive ESL does not appear to aggravate POS or sGTC seizures.
研究加用醋酸艾司利卡西平（ESL）是否会导致部分患者癫痫发作加剧。
对三项ESL辅助治疗（研究301、302和304）难治性局灶性发作（POS）的III期试验汇总数据进行事后分析。在8周的基线期后，患者被随机分配接受安慰剂或每日一次400、800或1200mg的ESL（2周滴定期、12周维持期、2 - 4周减量期）。汇总患者癫痫发作日记数据和癫痫治疗中出现的不良事件（TEAE）报告进行分析。
改良意向性治疗人群和安全性人群分别包括1410例患者和1447例患者。：与安慰剂组（32/21%）相比，服用800mg ESL（20/15%）和1200mg ESL（22/12%）的患者中，标准化癫痫发作频率（SSF）较基线增加≥25/≥50%的比例显著更小；安慰剂组和400mg ESL组之间无显著差异。：与安慰剂组（20%）相比，服用ESL（400mg，12%；800mg，12%；1200mg，14%）的患者中，SSF增加≥25%的比例显著更小。在评估SSF增加≥50%时，只有800mg ESL组（7%）与安慰剂组（12%）有显著差异。一些患者在基线期无继发性全面强直 - 阵挛（sGTC）发作，但在维持治疗期间出现≥1次sGTC发作（安慰剂组，11%；400mg ESL组，5%；800mg ESL组，10%；1200mg ESL组，5%）。服用ESL（400mg，11%；800mg，9%；1200mg，14%）的患者中，sGTC发作频率增加≥25%的人数少于安慰剂组（19%）。所有治疗组中报告为TEAE的癫痫发作发生率较低；ESL组的发生率总体低于安慰剂组。：服用ESL和安慰剂的患者中，SSF增加≥25/≥50%的比例相似。ESL组癫痫TEAE发生率在数值上高于安慰剂组。
ESL辅助治疗似乎不会加重POS或sGTC发作。
