415_2017_8621_moesm1_esm.docx - springer …10.1007... · web viewgbp 2400 mg/3600 mg 52vgb 2000...

Table S1. Characteristics of the included studies in this network meta-analysis.

Study Multicenter Study design

Age (range) Male/female Seizure type

(etiology)

Patient (n)efficacy analysis

based on theITT population

Baseline seizure frequency/28 d

(median)

Duration of maintenance period+titrati

on

Analysis results

Other AEDs

ESL

Elger et al. 2009 Europe P 18–76 years 196/206 SPS, CPS,

SGS

Placebo102ESL 400 mg 99ESL 800 mg 98ESL 1200 mg 98

6.7/7.5/7.0/7.4 12+2 ITT <3 AEDs

Gil-Nagel et al. 2009Mexico,

Portugal and Spain

P 17–77 years 113/139 SPS, CPS,

SGS

Placebo 84, ESL800 mg 84

ESL 1200 mg 7711.3/11.6/11.3 12+2 ITT 1 or 2

Ben-Menachem et al. 2010

Europe, South Africa, P ≥18 years 194/201 SPS, CPS,

SGS

Placebo 100, ESL 400 mg 96,

ESL 800 mg 100, ESL 1200 mg 97

8.0/8.0/9.0/9.0 14+2 ITT 1 to 3

Sperling et al.2015

Europe, Australia,

Brazil, Canada, India,

South,Korea, Romania, South

Africa, and USA

P ≥16 years 326/324 SPS, CPS, SGS

Placebo 220; ESL 800 mg 215; ESL 1,200 mg 205

8/8/9 12+2 ITT 1 or 2

GBP

The US Gabapentin Study Group 1993 United States P ≥16 years 202/104 SPS, CPS,

SGS

Placebo 98; GBP 600 mg 53;

GBP 1200 mg 101; GBP 1800 mg 54

10.7/10/11/12.7 12 Not stated

<3 AEDs

UK gabapentin study group 1990 Not stated P 14-73

years 53/74 SPS, CPS, SGS

Placebo 66 GBP 1200 mg 61 13/13 12+2 ITT 1 or 2

Anhut et al. 1994

Europe, Australia,

Canada, South Africa

P 12-67 years 152/120 SPS, CPS,

SGS

Placebo 109GBP 900 mg 111 GBP 1200 mg 52

9.3/10.3/ 9.8 12 ITT 1 or 2

Appleton et al. 1999

Europe,South Africa, and the United

States

P ≤12 years 134/113SPS or partial

becoming generalized

Placebo128, GBP 600-1800 mg

119 28.0/24.1/26.7 12 ITT 1 to 3

Yamauchi et al. 2006 Japan P 16 years 101/108 Partial seizures

Placebo 82GBP 1200 mg 86GBP 1800 mg 41

9.7/11.2/12.3 12 not stated 2 or 3

PGB

Lee et al. 2009 Korea P ≥18 years 86/92 SPS, CPS, SGTC

Placebo 59 PGB 600 mg 119 5.2/6.7 12 ITT 1 to 4

Arroyo et al. 2004Australia,

Europe South Africa,

P ≥18 years 145 /142 partial

seizures (SPS, CPS, SGTC)

Placebo 96, PGB 150 mg 99, PGB 600 mg 92

9.3/11.5/12.3 12 ITT 1 to 3

Beydoun et al. 2005 United States, Canada. P ≥18 years 156 /156

partial seizures (SPS, CPS, SGTC)

Placebo 98; PGB 600 mg BID 103; PGB 600 mg

TID 111

11/9.5/10 11+1 ITT Not stated

French et al. 2014United States, Europe, Asia,

All OtherP ≥18 years 154/169

Partial seizures with

or without SGS

Placebo 110, PGB 165 mg 100, PGB 330 mg 113

7.0/6.9/7.4 12+2 ITT 1 to 3 or up to3

Elger et al. 2005 Canada, Europe P 18–78 years 170/171 Partial

seizures

Placebo73; PGB 150 600 mg 131

PGB 600 mg 1378.7/9.33/10 12 ITT 1 to 3 or

up to3

French et al2003 America and Canada P 12–75

years 220/235 SPS, CPS, SGTC

Placebo100PGB 100 mg 88PGB 300 mg 86PGB 600 mg 90PGB 1200 mg 89

9.5/10.3/8.8/9.8/9 12 ITT 1 to 3

CRS

Halford et al. 2011 Not stated P 16–73 years 269/278 SPS, CPS,

SGS

Placebo 183, CRS 800 mg 176, CRS 1200 mg 181

8/8/7.9 12+2 ITT 1 to 3

Faught et al. 2008 Not stated P 17–68 years 253/280 SPS, CPS,

SGS

Placebo 109, CRS 100 mg 105,CRS 300 mg 106, CRS 800 mg 108, CRS1600 mg 105

not stated 12+4 ITT 10 or fewer

GBP-VGB

Lindberger et al. 2000 Scandinavia P 12–75 years 51 /51 Partial

seizures

GBP 2400 mg/3600 mg 52

VGB 2000 mg/4000 mg 50

Not stated 8 +8 ITT 1 or 2

LCS

Halasz et al. 2009 Europe and America P 16–70


Placebo 159; LCM200 mg 160; LCM 400 mg 158

9.9/11.5/10.3 12 ITT ≥2

Chung et al. 2010 United States P 16–70 years 200/205 POS, with or

without SGS

Placebo 104; LCM 400 mg 201; LCM 600 mg 97;

15.0/11.5/16.5 12+6 ITT 2 or 3


Europe and America P 18–68


Placebo 96 LCM 200 mg 107 LCM 400 mg 107 LCM 600 mg 105

Not stated 12+6 ITT ≥2

LTG

Boas et al. 1996 Denmark. C 16–65 years Not stated

Partial seizure with or

without SGS

Placebo/LTG 26 LTG/Placebo 30 Not stated 12 Not

stated 0 to 3

Naritoku et al. 2007 America, Europe, Asia P >12 years 117/119


without SGS

Placebo 120 LTG 116 8.4/9.2 12 ITT 1 or 2

Messenheimer et al. 1994 Not stated C 18–65


Placebo 44 LTG 44 12.3/13.3 14 ITT

Duchown et al. 1999 United States and France P 2–16 years 103/96 SPS, CPS,

SGSPlacebo 101

LTG 98 Not stated 12+6 ITT 1 or 2

LEV



years 137/149 CPS Placebo 105LEV 3000 mg 181 7/6.76 14+4 ITT 1 or 2

Shorvon et al. 2000 Europe P 16–68 years 157/167


without SGS

Placebo 112LEV 1000 mg 106LEV 2000 mg 106

2.5/2.82/2.58 12 ITT 1 or 2

Xiao et al. 2009 China P 17–60 years 24/32


without SGS

Placebo 28LEV 3000 mg 28 Not stated 12+4 ITT 1 or 2

Zhou et al. 2008 China P 16–70 years 13/11


without SGS

Placebo11LEV 3000 mg 13 Not stated 12+4 ITT Not

stated

Tsai et al. 2006 Taiwan P 16–60 years 42/52


without SGS

Placebo 47LEV 2000 mg 47 8/6.4 12+2 ITT 1 or 2

Boon et al. 2002 Europe C 16–69 years 157/167


without SGS

Placebo 200LEV 1000 mg 200 LEV 2000 mg 202

Not stated 12 +4 ITT 1 or 2

Glauser et al. 2006 Not stated P 4–16 years 111/87 SPS, CPS, SGS

Placebo 97 LEV 101 Not stated 10+4 ITT 1 or 2

Cereghino et al. 2000 Not stated P 16–70 years 178/116


without SGS

Placebo 95LEV 1000 mg 98

LEV 3000 mg 1017.08/10.12/8.32 14+4 ITT >2

Peltolta et al. 2009 Not stated P 12–70 years 99/59


without SGS

Placebo 79LEV XR 1000 mg 79 8.44/7.2 12 ITT 1 to 3

Inoue et al. 2015 Japan P 16–65 years 171/180 POS

Placebo 70 LEV 500 mg 71 LEV 1000 mg 70 LEV 2000 mg 70 LEV 3000 mg 70

12/10.68/11/12.84/10.6 12+4 ITT 1 to 3

Wu et al. 2009 China P 16–70 years 105/97 POS, with or

without SGSPlacebo 100

LEV 1500 mg 102 Not stated 12+4 ITT 1 or 2

Levisohn et al. 2009

United States, Canada,

and South Africa

P 4–16 years 56/42 CPS, SPS and SGS

Placebo 34 LEV 64 Not stated 8+4 ITT 1 or 2

PGB- LEV

Zaccara et al. 2014

Western and Eastern Europe,

South and Central

America, and Asia

P ≥18 years 245/264

Partial seizures with

or without SGS

PGB 600 mg 254 LEV 3000 mg 255 7.8/7.5 12+4 ITT 1 or 2

OXC

Barcs et al. 2000 America P 16–68 years 341/351


without SGS

Placebo 173OXC 600 mg 168OXC 1200 mg 177OXC 2400 mg 174

8.6/9.6/9.8/10 24 ITT 1 to 3

Glauser et al. 2000 Caucasian P 3–17 years 141/126Partial

seizures SPS, CPS, SGS

Placebo 129 OXC 138 12a/13 14+2 ITT 1 or 2

French et al. 2014North America;

Eastern Europe/Russia;

P 18–65 years 202/164

POS, with or without

SGS

Placebo 121 OXC* 1200 mg 122 OXC* 240 mg 123

7.0/6.0/6.0 12+4 ITT 1 to 3

PER

French et al. 2013

Australia, Europe India, Israel, United

States, and South Africa.

P ≥12 years 86//300 CPS, SPS, or SGS

Placebo 136 PER 8 mg 129 PER 12 mg 121

11.8/13.0/13.7 13+6 ITT Not stated

French et al. 2012

Argentina, Canada, Chile,

Mexico, and the United States

P ≥12years 188/200 POS with or without SGS

Placebo 121 PER l8 mg 133 PER12 mg 134

13.7/14.3/12.0 13+6 ITT 1 to 3

Krauss et al. 2012 Europe, India, and China P ≥12 years 345/361 CPS, SPS, or

SGS

Placebo 184 PER 2 mg 180 PER 4 mg 172 PER 8 mg1 69

9.3/10.1/10.0/10.9 13+6 ITT 1 to 3

Lagae et al. 2016

India, Hungary, Latvia, United

States, Thailand, Spain

and others

P 12–17 years 80/53 CPS and SGS Placebo 48

PER 85 not stated 13+6 not stated 1 to 3

PGB-LTG

Baulac et al. 2010Europe,

Canada, and Australia

P ≥18 years 210/223 Partial seizures

Placebo 141 PGB 300/600 mg 152 LTG 300/400 mg 141

7.33/9.33/8.67 11+6 ITT 1 to 3

RTG

Porter et al. 2007

Europe, Australia, and

the United States

P 16–70 years 204/196 POS (SPS,

CPS, SGS)

Placebo 96 RTG 600 mg 99 RTG 900 mg 95

RTG 1200 mg 106

8.5/8.5/7.9/10.4 8+8 ITT 1 or 2

Brodie et al. 2010

Australia, Europe, South Africa, and the United States

P 18–75 years 258/281

Refractory partial

epilepsy


9.3/9.5/10.3 12+4 ITT 1 to 3

French et al. 2011

United States, Canada, Mexico,

Argentina, and Brazil

P 18–75 years 140/165 SPS, CPS,

SGSPlacebo 152

RTG 154 11.3/12.1 12+6 ITT 1 to 3 or VNS

Lim et al. 2016 Asian P ≥18 years 45/30 SPS, CPS, SGS


Not stated 12+4 ITT 1 to 3

TGB

Uthman et al. 1998 America P 12–77 years 172/125 SPS, CPS,

SGS

Placebo 90TGB 16 mg 61TGB 32mg 86TGB 56 mg 55


Kalvianinen et al. 1998 Europe P 16–75 years 90/64 SPS, CPS,

SGSPlacebo 77

TGB 30 mg 77 10.5/12.2 22 ITT 1 to 3

Sachdeo et al. 1997 United States P 12–75 years 178/140 SPS, CPS,

SGS

Placebo 107 TGB16 mg 106 TGB 4 mg 105


TPM

Yen et al. 2000 Taiwan P 18–65 years 19/27 SPS, CPS,

SGSPlacebo 23

TPM 600 mg 23 Not stated 14 ITT 1 or 2

Faught et al. 1996 Europe P 19–68 years 143/88 SPS, CPS,

SGS

Placebo 45TPM 200 mg 45TPM 400 mg 45TPM 600 mg 46

10/11.5/11/11.2 12 +4 ITT 1 or 2




Placebo 28TPM 800 mg 28 11.4/14.2 8+5 ITT 1 or 2

Privitera et al. 1996 Europe and America P 18–68


Placebo 47TPM 600 mg 48TPM 800 mg 48TPM 1000 mg 47

9.3/10/16.2/11.7 12 +6 ITT 1 or 2

Sharief et al. 1996 Europe P 18–65 years 40/7 SPS, CPS,

SGSPlacebo 24

TPM 400 mg 23 10/18 8 ITT 1 or 2

Zhang et al. 2011 China P ≥65 years 49/37 SPS, CPS, SGS

Placebo 40 TPM 46 17.3/16.9 12+8 ITT 1 to 3

Korean Topiramate Study Group 1999 Korea P 16–65

years 95/82 Placebo 86 TPM 91 5.6/5.6 10+8 ITT 1 or 2

Elterman et al. 1999 United States; Costa Rica P 1–16 years 48/38

POS with or without

SGSPlacebo 45

TPM 125-400 mg 41 19/22 8+8 ITT 1 or 2

Chung et al. 2014

Argentina,Australia, Belgium,

Canada, Chile, India, Israel,

Europe, SouthAfrica, the

United States

P 18–75 years 132/117 SPS, CPS,

SGSPlacebo 125 TPM** 124 Not stated 8+3 ITT ≥3 AED

VPA

Brodie et al. 1999 Not stated P 12–75 years 196/109 SPS, CPS,

SGS

VGB 2000-4000 mg 108;

VPA 1000-2000 mg 107

6.8/6.9 12+8 ITT Not stated

VGB

Bruni et al. 2000 Canada P 16–50 years 61/50 SPS, CPS,

SGSPlacebo 53

VGB 4000 mg 58 8.6/7.3 32+4 ITT 1 or 2

French et al. 1996 Europe P 18–60 years 80/102 SPS, CPS,

SGSPlacebo 90

VGB 3000 mg 92 Not stated 12 +4 Not stated 1 or 2

Dean et al. 1999 Not stated P 18–60 years 83/91 SPS, CPS,

SGS

Placebo45 VGB 1000 mg 45 VGB 3000 mg 43 VGB 6000 mg 41

9/8.5/8/9 12+6 ITT 1 or 2

Beran et al. 1996 Caucasian C 17–64 years 41/39 CPS

VGB 2 g/Placebo 20 Placebo/VGB 2 g 22 VGB 3 g/Placebo 20 Placebo/VGB 3 g 18

15.4/9.4 8+4 Not stated 1 to 3

ZNS

Brodie et al. 2004 Europe P 18–59 years 89/59 SPS Placebo 69

ZNS 400 mg 68 Not stated 8 ITT Not stated

Faught et al. 2001 America C 14–68 years 104/99 SPS, CPS,

SGSPlacebo 72

ZNS 400 mg 98 Not stated 12 ITT 1 or 2

Sackarelles et al. 2004 America P 18–68 years 111/51 SPS, CPS,

SGSPlacebo 72

ZNS 7 mg/kg 78 9.6/9.1 12 ITT 1 or 2

Schmidt et al. 1993 Europe P 18–59 years 81/59 CPS Placebo 68

ZNS 7 mg/kg 71 9.7/10 12 ITT Not stated

Brodie et al. 2005 Europe and South Africa P 12–77


Placebo 119ZNS 100 mg 55ZNS 300 mg 55

ZNS 500 mg 118

5.7/6.3/2.9/6.2 18+3 ITT Not stated

Guerrini et al. 2013 Europe and India P 6-17 years 108/99

POS, with or without

SGSPlacebo100

ZNS 8 mg/kg/day 107 10/10.5 12+8 ITT 1 or 2

RUF

Brodie et al. 2009

USA, Argentina,

Europe, South Africa

P ≥16 years 139/174 SPS, CPS, SGS

Placebo 156 RUF 1600 mg 156 8.5/8.0 11+2 ITT 1 or 2

BRV

Klein et al. 2015

North America, Europe, Latin America, and

Asia

P 16–80 years 288/376 POS

Placebo 259 BRV 100 mg 252 BRV 200 mg 249

10.0/9.5/9.3 12 ITT 1 or 2

Ryvlin et al. 2014 Europe P 16–70 years 277/121

Focal seizures with or without

SGS

Placebo 100 BRV 20 mg 99 BRV50 mg 99

BRV100 mg 100

Not stated 12 ITT 1 to 3, or up to3

NOTES: LCM: Lacosamide; CRS: Carisbamate; ESL: Eslicarbazepine acetate; GBP: Gabapentin; LTG: Lamotrigine; LEV: Levetiracetam; OXC: Oxcarbazepine; PER:

Perampanel; PGB: Pregabalin; RTG: Retigabine; TPM: Topiramate; VGB: Vigabatrin; VPA: Valproate; ZNS: Zonisamide; RUF: Rufinamide; TGB: Tiagabine; BRV:

Brivaracetam; PBO: Placebo; ITT: Intention-To-Treat; C: crossover; P: parallel-group; SPS: simple partial seizure; CPS: complex partial seizure; SGS: secondary

generalization seizure ; POS: partial-onset seizure; SGTC: secondarily generalized tonic--clonic seizures; *: SPN-804; **: USL255

Table S2. Network meta-analysis results of the seizure freedom of maintance period treatment for partical-onset epilepsy in different AEDs.

LCM 1.02 (0.09, 7.02)

0.77 (0.05, 3.21)

4.10 (0.57, 15.16)

1.09 (0.14, 4.20)

2.07 (0.19,21.57)

0.86 (0.08,5.11)

0.49 (0.03,4.01)

0.84 (0.06,3.87)

0.38 (0.06,0.89)

0.98 (0.14, 10.84) ELS 0.71

(0.08,4.67)3.79

(0.66, 26.98)1.04

(0.17, 7.26)1.91

(0.24,31.96)0.81

(0.10,7.14)0.47

(0.03,6.08)0.78

(0.08,6.30)0.36

(0.07,1.49)

1.30 (0.31, 18.42)

1.42 (0.21, 12.31) LTG 5.12

(1.19, 38.75)

1.41 (0.32,11.23

)

2.55 (0.39,52.04)

1.12 (0.18,10.04)

0.65 (0.06,8.49)

1.07 (0.16,10.01)

0.48 (0.15,2.18)

0.24 (0.07, 1.75)

0.26 (0.04, 1.52)

0.20 (0.03, 0.84) LEV 0.28

(0.06, 1.19)0.53

(0.07, 6.08)0.22

(0.03,1.38)0.12

(0.01,1.20)0.21

(0.03,1.13)0.09

(0.03,0.23)0.92

(0.24, 7.30)0.96

(0.14, 6.01)0.71

(0.09, 3.15)3.52

(0.84, 15.90) PER 1.84 (0.27,22.68)

0.82 (0.11,4.97)

0.46 (0.04,4.04)

0.77 (0.09,4.57)

0.33 (0.10,0.88)

0.48 (0.05, 5.29)

0.52 (0.03, 4.09)

0.39 (0.02, 2.54)

1.88 (0.16, 14.18)

0.54 (0.04, 3.65) RTG 0.44

(0.03,3.61)0.23

(0.01,2.83)0.40

(0.02,3.24)0.19

(0.02,0.89)1.17

(0.20, 12.91)1.23

(0.14, 10.11)0.89

(0.10, 5.67)4.48

(0.73, 30.98)1.23

(0.20, 9.04)2.25

(0.28,39.61) TPM 0.58 (0.04,7.08)

0.95 (0.11,8.11)

0.42 (0.09,1.78)

2.04 (0.25, 39.86)

2.12 (0.16, 29.99)

1.54 (0.12, 16.56)

8.06 (0.83, 99.22)

2.19 (0.25,26.37

)

4.26 (0.35,107.91)

1.74 (0.14,27.60) ZNS 1.66

(0.11,23.02)0.75

(0.10,6.37)

1.20 (0.26, 17.40)

1.29 (0.16, 12.19)

0.94 (0.10, 6.11)

4.78 (0.89, 39.43)

1.30 (0.22,10.66

)

2.49 (0.31,45.33)

1.05 (0.12,9.45)

0.60 (0.04,8.79) TGB 0.46

(0.09,2.17)

2.62 (1.12, 17.44)

2.76 (0.67, 13.96)

2.09 (0.46, 6.77)

10.58 (4.38, 34.82)

3.06 (1.13,10.11

)

5.31 (1.12,58.51)

2.41 (0.56,11.26)

1.34 (0.16,10.44)

2.19 (0.46,10.61) PLA

Table S3. Network meta-analysis results of the seizure freedom of double blind period treatment for partial-onset epilepsy in different AEDs.

CRS1.81

(0.17, 28.30)

1.70 (0.23, 11.50)

2.32 (0.28, 16.68)

0.67 (0.09, 4.38)

1.30 (0.11, 18.86)

1.65 (0.21, 11.72)

1.41 (0.16, 12.29)

2.05 (0.17, 27.86)

0.73 (0.10, 5.27)

0.16 (0.01, 1.98)

1.95 (0.20, 19.06)

0.35 (0.06, 1.80)

0.55 (0.04, 5.76)

ESL0.95

(0.09, 6.48)

1.30 (0.10, 9.56)

0.38 (0.03, 2.21)

0.76 (0.04, 9.09)

0.92 (0.08, 6.73)

0.79 (0.06, 6.43)

1.17 (0.06, 14.13)

0.42 (0.04, 2.68)

0.08 (0.00, 1.00)

1.14 (0.08, 9.82)

0.20 (0.02, 0.93)

0.59 (0.09, 4.33)

1.05 (0.15, 11.63)

LEV1.38

(0.30, 6.58)

0.40 (0.10, 1.52)

0.78 (0.10, 7.96)

0.96 (0.22, 4.56)

0.84 (0.17, 5.01)

1.24 (0.14, 12.04)

0.45 (0.10, 1.89)

0.09 (0.01, 0.81)

1.18 (0.20, 7.90)

0.21 (0.07, 0.56)

0.43 (0.06, 3.59)

0.77 (0.10, 10.13)

0.73 (0.15, 3.33)

OXC0.29

(0.06, 1.22)

0.57 (0.07, 5.87)

0.71 (0.15, 3.44)

0.60 (0.11, 3.93)

0.87 (0.09, 9.53)

0.33 (0.07, 1.49)

0.07 (0.01, 0.58)

0.84 (0.13, 5.85)

0.15 (0.04, 0.45)

1.50 (0.23, 10.94)

2.62 (0.45, 28.82)

2.51 (0.66, 9.73)

3.44 (0.82, 15.94)

PGB1.89

(0.28, 18.85)

2.42 (0.64, 10.27)

2.10 (0.44, 12.58)

3.09 (0.40, 31.81)

1.14 (0.28, 4.38)

0.24 (0.03, 1.82)

2.90 (0.53, 19.46)

0.52 (0.20, 1.24)

0.77 (0.05, 8.87)

1.31 (0.11, 24.69)

1.28 (0.13, 10.10)

1.77 (0.17, 14.40)

0.53 (0.05, 3.62)

RTG1.24

(0.12, 10.27)

1.09 (0.09, 10.94)

1.59 (0.10, 24.50)

0.57 (0.06, 4.41)

0.12 (0.01, 1.65)

1.53 (0.12, 17.65)

0.26 (0.03, 1.52)

0.61 (0.09, 4.85)

1.09 (0.15, 12.70)

1.04 (0.22, 4.50)

1.40 (0.29, 6.88)

0.41 (0.10, 1.55)

0.81 (0.10, 8.45)

TPM0.88

(0.15, 4.93)

1.28 (0.14, 12.15)

0.46 (0.10, 2.05)

0.09 (0.01, 0.81)

1.17 (0.19, 8.23)

0.21 (0.06, 0.60)

0.71 (0.08, 6.36)

1.26 (0.16, 15.66)

1.19 (0.20, 5.90)

1.65 (0.25, 9.19)

0.48 (0.08, 2.26)

0.92 (0.09, 10.61)

1.13 (0.20, 6.81)

VGB1.47

(0.34, 6.17)

0.54 (0.09, 2.60)

0.11 (0.01, 1.12)

1.41 (0.17, 9.98)

0.25 (0.06, 0.86)

0.49 (0.04, 5.98)

0.86 (0.07, 16.39)

0.80 (0.08, 6.90)

1.14 (0.10, 10.79)

0.32 (0.03, 2.50)

0.63 (0.04, 10.41)

0.78 (0.08, 7.33)

0.68 (0.16, 2.92)

VPA0.37

(0.04, 3.10)

0.08 (0.00, 1.08)

0.99 (0.07, 11.13)

0.17 (0.02, 1.07)

1.37 (0.19, 9.57)

2.36 (0.37, 26.23)

2.22 (0.53, 9.90)

3.05 (0.67, 15.16)

0.88 (0.23, 3.59)

1.75 (0.23, 16.70)

2.16 (0.49, 10.16)

1.87 (0.39, 11.12)

2.73 (0.32, 27.15)

ZNS0.21

(0.02, 1.73)

2.67 (0.40, 17.67)

0.46 (0.16, 1.23)

6.31 (0.50, 87.43)

11.80 (1.00,

218.43)

10.82 (1.23,

101.79)

14.57 (1.72,

155.64)

4.14 (0.55, 36.28)

8.26 (0.61,

147.13)

10.69 (1.24,

110.20)

9.13 (0.89, 98.42)

13.20 (0.93,

216.79)

4.77 (0.58, 46.95)

RUF12.30 (1.17,

172.26)

2.18 (0.34, 16.19)

0.51 (0.05, 5.08)

0.88 (0.10, 12.06)

0.84 (0.13, 5.00)

1.18 (0.17, 7.57)

0.34 (0.05, 1.89)

0.65 (0.06, 8.51)

0.86 (0.12, 5.29)

0.71 (0.10, 6.02)

1.01 (0.09, 13.59)

0.37 (0.06, 2.49)

0.08 (0.01, 0.85)

BRV0.18

(0.03, 0.78)

2.86 (0.56, 17.10)

5.01 (1.08, 47.44)

4.84 (1.79, 13.99)

6.51 (2.21, 23.03)

1.91 (0.81, 4.90)

3.79 (0.66, 31.22)

4.67 (1.67, 15.65)

4.04 (1.17, 17.67)

5.93 (0.93, 48.44)

2.15 (0.81, 6.13)

0.46 (0.06, 2.92)

5.68 (1.29, 29.98)

PBO

Figure S1. Flow chart of the selection process

Figure S2 Network plot of different inventions for safety

The size of the nodes corresponds to the number of trials that study the treatments. Directly comparable

treatments are linked with a line, the thickness of which corresponds to the number of trials that assess

the comparison. LCM: lacosamide; CRS: Carisbamate; ESL: Eslicarbazepine acetate; GBP:

Gabapentin; LTG: Lamotrigine ; LEV: Levetiracetam; OXC: Oxcarbazepine; PER: Perampanel;

PGB: Pregabalin; RTG: Retigabine; TPM: Topiramate; VGB: Vigabatrin; VPA: Valproate; ZNS:

Zonisamide; RUF: Rufinamide; TGB: Tiagabine; BRV: Brivaracetam ; PBO: Placebo

Figure S3A. The inconsistency test for efficacy measured by a loop specific model

In the loop, the lower limits of 95%Crl included 0 which shows a good consistency.

LEV: Levetiracetam; PGB :Pregabalin; PBO: Placebo

Figure S3B. The inconsistency test for efficacy measured by a loop specific model

In the two loops, the lower limits of 95%Crl included 0 which shows a good consistency. GBP:

Gabapentin; LEV: Levetiracetam; PGB: Pregabalin; PBO: Placebo; VGB:Vigabatrin.

Figure S4. Comparison-adjusted funnel plot for efficacy.

LCM: Lacosamide; CRS: Carisbamate; ESL: Eslicarbazepine acetate; GBP: Gabapentin; LTG:

Lamotrigine; LEV: Levetiracetam; OXC: Oxcarbazepine; PER: Perampanel; PGB: Pregabalin; RTG:

Retigabine; TPM: Topiramate; VGB: Vigabatrin; VPA: Valproate; ZNS: Zonisamide; RUF:

Rufinamide; TGB: Tiagabine; BRV: Brivaracetam; PBO: Placebo

Figure S5. Comparison-adjusted funnel plot for safety

LCM: Lacosamide; CRS: Carisbamate; ESL: Eslicarbazepine acetate; GBP: Gabapentin ; LTG:

Lamotrigine; LEV: Levetiracetam; OXC: Oxcarbazepine; PER: Perampanel; PGB: Pregabalin; RTG:

Retigabine; TPM: Topiramate; VGB: Vigabatrin; VPA: Valproate; ZNS: Zonisamide; RUF:

Rufinamide; TGB: Tiagabine; BRV: Brivaracetam; PBO: Placebo

Figure S6. Density plot

Figure S7. Iterative history diagram

In this picture, three chains have a good convergence.

Figure S8. Convergence of Markov chains was deemed to be achieved if plots of the Gelman–Rubin

statistics indicated that the widths of pooled runs and individual runs stabilized around the same value

and their ratio around 1. this picture showed Convergence of Markov chains obtain a good convergence

and Gelman–Rubin statistics found when 20000 iteration achieved, the convergence became stability.

415_2017_8621_moesm1_esm.docx - springer …10.1007... · web viewgbp 2400 mg/3600 mg 52vgb 2000...

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