Introduction
Methods
Study design
Study population
Study name (if applicable) Reference | Country/countries | Design | Population | Number of PWE |
---|---|---|---|---|
Published articles | ||||
Rohracher et al. [16] | Austria, France, Germany, Italy, Spain, Sweden, UK | Multicenter Pooled observational data | Several populations typically under-represented in clinical trials | 2396 |
Kim and Oh [17] | Korea | Single-center Prospective | PWE aged ≥ 17 years | 137 |
PERADON Abril Jaramillo et al. [18] | Spain | Multicenter Prospective | PWE aged ≥ 12 years with FOS and PER as first add-on therapy | 113 |
Santamarina et al. [19] | Spain | Multicenter Retrospective | PWE aged ≥ 12 years and PER as first add-on therapy | 144 |
GENERAL Villanueva et al. [20] | Spain | Multicenter Retrospective | People aged ≥ 12 years with IGE | 149 |
PERADET Coppola et al. [21] | Italy | Multicenter Prospective | Adult PWE with brain tumor | 14 |
Toledo et al. [22] | Spain | Multicenter Prospective | PWE aged ≥ 16 years with FOS (sleep quality study) | 72 |
Strzelczyk et al. [23] | Austria, Finland, Germany, Spain | Multicenter Retrospective | Adults with status epilepticus | 52 |
Gil-López et al. [24] | Spain | Multicenter Retrospective | PWE aged ≥ 16 years with myoclonic seizures | 31 |
Auvin et al. [25] | France | Single center Prospective | Children and adults with Lennox-Gastaut syndrome | 13 |
Alsaadi et al. [26] | United Arab Emirates | Single center Retrospective | People with IGE treated with PER monotherapy | 21 |
Izumoto et al. [27] | Japan | Single center Prospective | Adult PWE with brain tumor | 12 |
Deleo et al. [28] | Italy | Multicenter Prospective | PWE aged ≥ 16 years with drug-resistant focal epilepsy | 56 |
Maschio et al. [29] | Italy | Multicenter Retrospective | Adult PWE with brain tumor | 27 |
Steinhoff et al. [30] | Germany | Single center Retrospective | Adult PWE | 92 |
Rea et al. [31] | Italy | Multicenter Retrospective | Adult PWE and PER as first add-on therapy | 27 |
Toledano et al. [32] | Spain | Multicenter Retrospective | PWE aged ≥ 12 years and PER monotherapy | 98 |
Moraes et al. [33] | Australia | Prospective Retrospective | Adult PWE | 93 |
Chiang et al. [34] | Taiwan | Multicenter Retrospective | PWE aged ≥ 16 years | 229 |
Datta et al. [35] | Canada | Single center Retrospective | Pediatric population with epilepsy | 24 |
Coyle et al. [36] | UK | Single center Retrospective | Adult PWE | 23 |
Ho et al. [37] | Taiwan | Single center Retrospective | PWE with refractory status epilepticus | 22 |
De Liso et al. [38] | Italy | Multicenter Retrospective | Children and adolescents with refractory epilepsy | 62 |
Italy | Single center Retrospective | Adult PWE | 96 | |
Takahashi et al. [41] | Japan | Multicenter Retrospective | PWE with FOS and PER as early add-on vs. late add-on therapy | 51 |
Morano et al. [42] | Italy | Single center Retrospective | PWE with highly refractory epilepsy | 89 |
Goji and Kanemoto [43] | Japan | Single center Prospective | Adult PWE | 128 |
Rocamora et al. [44] | Spain | Retrospective | Adult PWE | 77 |
Gil-Nagel et al. [45] | Spain | Multicenter Retrospective | Monotherapy | 60 |
Vlasov et al. [46] | Russia | Multicenter Retrospective | PWE with focal epilepsy | 164 |
Abstracts | ||||
Teijeira et al. [47] | Spain | Single center | PWE aged ≥ 12 years and PER as first add-on therapy or monotherapy | 26 |
Ron et al. [48] | Spain | Multicenter Prospective | Children with epilepsy | 14 |
Carreño et al. [49] | Spain | Single center Retrospective | PWE with seizures exclusively during sleep | 98 |
Yamamoto [50] | Japan | Retrospective | PWE with PER as early add-on vs. late add-on therapy | 70 |
Pereagal Osorio et al. [51] | Spain | Multicenter Retrospective | Adult PWE with FOS and PER as early add-on therapy | 77 |
Odintsova [52] | Russia | – | PWE | 49 |
Matricardi et al. [53] | Italy | Multicenter Retrospective | PWE with FOS and Lennox-Gastaut syndrome | 58 |
Valente Fernandes (unpublisheda) | Portugal | – | Brain tumor | 7 |
Chinvarun [54] | Thailand | – | PWE and PER monotherapy | 41 |
Kristensen [55] | Norway | Single center Retrospective | PWE with FOS and PGTCS | 44 |
Bonanni et al. [56] | Italy | – | PWE with intellectual disability | 55 |
Local databases | ||||
Morillob | Canada | – | Adult PWE | 41 |
Suller Martic | Canada | – | Adult PWE | 5 |
Jacobs-LeVand | Canada | – | – | 36 |
Study assessments
Statistical analyses
Analysis populations
Statistical considerations and methods
Bivariate and multivariate analyses
Results
Study population
Characteristic | Full Analysis Set | Retention Population | Effectiveness Population | Tolerability Population |
---|---|---|---|---|
N = 5193 | N = 4721 | N = 4392 | N = 4617 | |
Sex | ||||
Na | 5175 | 4717 | 4376 | 4602 |
Female, n (%) | 2612 (50.5) | 2365 (50.1) | 2182 (49.9) | 2348 (51.0) |
Male, n (%) | 2563 (49.5) | 2352 (49.9) | 2194 (50.1) | 2254 (49.0) |
Age | ||||
Na | 4946 | 4555 | 4309 | 4443 |
Mean (SD), years | 39.7 (16.2) | 39.6 (15.9) | 39.5 (16.2) | 39.7 (16.1) |
Median (range), years | 38.6 (2.0‒97.0) | 38.0 (2.0‒97.0) | 38.0 (2.0‒92.0) | 38.0 (2.0‒97.0) |
Age category | ||||
Na | 5006 | 4606 | 4309 | 4503 |
< 12 years, n (%) | 64 (1.3) | 48 (1.0) | 50 (1.2) | 55 (1.2) |
≥ 12‒ < 18 years, n (%) | 279 (5.6) | 266 (5.8) | 258 (6.0) | 258 (5.7) |
≥ 18‒ < 65 years, n (%) | 4284 (85.6) | 3964 (86.1) | 3681 (85.4) | 3854 (85.6) |
≥ 65 years | 379 (7.6) | 328 (7.1) | 320 (7.4) | 336 (7.5) |
Age at epilepsy onset | ||||
Na | 4122 | ‒ | ‒ | ‒ |
Mean (SD), years | 16.1 (17.2) | |||
Median (range), years | 12.0 (0.0‒97.0) | |||
Duration of epilepsy | ||||
Na | 4228 | 4051 | 3632 | 3748 |
Mean (SD), years | 23.5 (16.0) | 23.5 (16.0) | 23.4 (16.0) | 23.7 (16.1) |
Median (range), years | 21.0 (0.0‒82.0) | 21.0 (0.0‒82.0) | 21.0 (0.0‒82.0) | 21.9 (0.0‒82.0) |
Etiologyb | ||||
Na | 3830 | ‒ | ‒ | ‒ |
Structural, n (%) | 2013 (52.6) | |||
Unknown, n (%) | 1199 (31.3) | |||
Genetic, n (%) | 475 (12.4) | |||
Infectious, n (%) | 107 (2.8) | |||
Immune, n (%) | 31 (0.8) | |||
Metabolic, n (%) | 3 (0.1) | |||
Other, n (%) | 2 (0.1) | |||
Epilepsy syndrome | ||||
Na | 2495 | ‒ | ‒ | ‒ |
No, n (%) | 2037 (81.6) | |||
Yes, n (%) | 458 (18.4) | |||
Vascular etiology | ||||
Na | 2495 | ‒ | ‒ | ‒ |
No, n (%) | 2371 (95.0) | |||
Yes, n (%) | 124 (5.0) | |||
Tumor etiology | ||||
Na | 2495 | ‒ | ‒ | ‒ |
No, n (%) | 2360 (94.6) | |||
Yes, n (%) | 135 (5.4) | |||
Learning disability | ||||
Na | 2626 | ‒ | ‒ | ‒ |
No, n (%) | 1890 (72.0) | |||
Yes, n (%) | 736 (28.0) | |||
Psychiatric comorbidity | ||||
Na | 2661 | ‒ | ‒ | ‒ |
No, n (%) | 2027 (76.2) | |||
Yes, n (%) | 634 (23.8) | |||
Most frequent typesc of psychiatric comorbidity | ||||
Na | 2661 | ‒ | ‒ | ‒ |
Depression, n (%) | 111 (4.2) | |||
Anxiety, n (%) | 89 (3.3) | |||
Hyperactivity, n (%) | 26 (1.0) | |||
Seizure type | ||||
Na | 4083 | ‒ | ‒ | ‒ |
Focal | 3911 (81.4) | |||
Generalized | 604 (12.6) | |||
Both focal and generalized | 214 (4.5) | |||
Status epilepticus | 74 (1.5) | |||
Number of previous ASMs | ||||
Na | 3999 | 3760 | 3407 | 3568 |
Mean (SD) | 4.9 (3.9) | 4.9 (3.9) | 4.9 (3.9) | 4.8 (3.9) |
Median (range) | 4.0 (0‒19) | 4.0 (0‒19) | 4.0 (0‒19) | 4.0 (0‒19) |
Number of previous ASMs | ||||
Na | 3999 | ‒ | ‒ | ‒ |
0, n (%) | 451 (11.3) | |||
1, n (%) | 428 (10.7) | |||
2, n (%) | 459 (11.5) | |||
3, n (%) | 405 (10.1) | |||
4, n (%) | 353 (8.8) | |||
5, n (%) | 296 (7.4) | |||
≥ 6, n (%) | 1607 (40.2) | |||
Most frequently usedd previous ASMs | ||||
Na | 1332 | ‒ | ‒ | ‒ |
Levetiracetam, n (%) | 330 (24.8) | |||
Valproate, n (%) | 300 (22.5) | |||
Carbamazepine, n (%) | 261 (19.6) | |||
Topiramate, n (%) | 261 (19.6) | |||
Lamotrigine, n (%) | 182 (13.7) | |||
Phenytoin, n (%) | 170 (12.8) | |||
Number of concomitant ASMs | ||||
Na | 4916 | 4561 | 4185 | 4344 |
Mean (SD) | 2.2 (1.2) | 2.3 (1.1) | 2.2 (1.1) | 2.3 (1.1) |
Median (range) | 2.0 (0‒7) | 2.0 (0‒7) | 2.0 (0‒7) | 2.0 (0‒7) |
Number of concomitant ASMs | ||||
Na | 4916 | ‒ | ‒ | ‒ |
0, n (%) | 269 (5.5) | |||
1, n (%) | 1031 (21.0) | |||
2, n (%) | 1681 (34.2) | |||
3, n (%) | 1313 (26.7) | |||
≥ 4, n (%) | 622 (12.7) | |||
Most frequently usedd concomitant ASMs | ||||
Na | 4756 | ‒ | ‒ | ‒ |
Levetiracetam, n (%) | 1777 (37.4) | |||
Valproate, n (%) | 1172 (24.6) | |||
Lamotrigine, n (%) | 1120 (23.5) | |||
Carbamazepine, n (%) | 1028 (21.6) | |||
Lacosamide, n (%) | 930 (19.6) | |||
Clobazam, n (%) | 750 (15.8) | |||
Zonisamide, n (%) | 617 (13.0) | |||
Topiramate, n (%) | 507 (10.7) | |||
Oxcarbazepine, n (%) | 486 (10.2) | |||
Types of concomitant ASMs | ||||
Na | 4756 | 4408 | 4028 | 4184 |
Enzyme inducers,e n (%) | 2365 (49.7) | 2250 (51.0) | 2048 (50.8) | 2134 (51.0) |
Sodium channel blockers,f n (%) | 3368 (70.8) | ‒ | ‒ | ‒ |
ASMs targeting the GABA system,g n (%) | 1507 (31.7) | ‒ | ‒ | ‒ |
Calcium channel blockers,h n (%) | 254 (5.3) | ‒ | ‒ | ‒ |
Potassium channel blockers,i n (%) | 93 (2.0) | ‒ | ‒ | ‒ |
Synaptic vesicle protein-2 modulators,j n (%) | 1809 (38.0) | ‒ | ‒ | ‒ |
ASMs with mixed mode of action,k n (%) | 2022 (42.5) | ‒ | ‒ | ‒ |
PER treatment and concomitant ASMs (FAS)
Retention (Retention Population)
Effectiveness (all PWE except those with status epilepticus; Effectiveness Population)
Change in seizure frequency by seizure type
Responder rate
Seizure freedom rate
Percentage of PWE with worsened seizure frequency
Effectiveness in PWE with status epilepticus (Effectiveness Population)
Safety and tolerability (Tolerability Population)
Total PWE | N = 4617 |
---|---|
PWE with any AE | |
Na | 4617 |
n (%) | 2303 (49.9) |
Most frequently reported AEsb | |
Na | 4617 |
Dizziness/vertigo, n (%) | 701 (15.2) |
Somnolence, n (%) | 491 (10.6) |
Irritability, n (%) | 386 (8.4) |
Behavioral disorders, n (%) | 249 (5.4) |
Instability/ataxia, n (%) | 188 (4.1) |
Fatigue, n (%) | 170 (3.7) |
Mood disturbance, n (%) | 100 (2.2) |
Weight increased, n (%) | 94 (2.0) |
Headache, n (%) | 77 (1.7) |
Anxiety, n (%) | 70 (1.5) |
Aggression, n (%) | 64 (1.4) |
Depression, n (%) | 55 (1.2) |
PWE with AEs leading to discontinuation | |
12 months | |
Na | 4201 |
n (%) | 739 (17.6) |
Longer term (> 12 months) | |
Na | 4164 |
n (%) | 856 (20.6) |
PWE with any psychiatric AE | |
Na | 4590 |
n (%) | 965 (21.0) |
PWE with psychiatric AEs leading to discontinuation | |
Na | 4294 |
n (%) | 414 (9.6) |
Most frequently reported psychiatric AEs leading to discontinuationb | |
Na | 4617 |
Irritability, n (%) | 141 (3.1) |
Behavioral disorders, n (%) | 127 (2.8) |
Mood disturbance, n (%) | 53 (1.1) |