Supplementary Table E-2 Baseline Characteristics of Participants Enrolled in Second Monotherapy

Supplementary Figure e-1

Supplementary Table e-1 Baseline characteristics of 2nd monotherapy cohort (Group 1), participants experiencing long term initial monotherapy success and not enrolled in 2nd monotherapy (Group 2), and participants experiencing treatment failure on initial monotherapy and not part of the 2nd monotherapy cohort (Group 3)

Name / Group 1: Initial therapy failure and enrolled in second therapy study
(n-208) / Group 2: Initial therapy successful
(n=129) / Group 3: Initial therapy failure and not participated in second therapy study (n=109) / Group 1
Versus
Group 2 / Group 1
Versus
Group 3 / Group 2
Versus
Group 3
Demographics and Anthropometrics
Age (years) (mean, SD) / 7.6 (2.2) / 7.7 (2.1) / 7.7 (2.2) / 0.79 / 0.69 / 0.89
BMI / 17.4 (2.8) / 17.4 (2.6) / 17.6 (2.4) / 0.80 / 0.42 / 0.60
BMI-Z / 0.5 (1.0) / 0.5 (0.9) / 0.6 (0.9) / 0.47 / 0.28 / 0.71
Sex Male (n, %) / 84 (40.4) / 59 (45.7) / 49 (45.0) / 0.37 / 0.47 / 1.0
Hispanic ethnicity (n, %) / 47 (22.6) / 29 (22.5) / 24 (22.0) / 1.0 / 1.0 / 1.0
Race / 0.34 / <0.001 / 0.054
Black (n, %) / 27 (13.0) / 24 (18.6) / 35 (32.1)
White (n, %) / 165 (79.3) / 97 (75.2) / 69 (63.3)
Other (n, %) / 16 ( 7.7) / 8 ( 6.2) / 5 ( 4.6)
Continuous Performance Test
Confidence index (mean, SD) / n=187 / n=120 / n=92
Mean, SD / 54.5 (24.1) / 53.7 (26.2) / 58.5 (23.8) / 0.78 / 0.19 / 0.17
≥ 0.6 (n, %) / 65 (34.8) / 39 (32.5) / 38 (41.3) / 0.71 / 0.29 / 0.20
Omission T-score (n, %) / n=191 / n=122 / n=94
< 60 / 126 (66.0) / 84 (68.9) / 56 (59.6) / 0.12 / 0.28 / 0.29
60-70 / 30 (15.7) / 10 (8.2) / 13 (13.8)
>70 / 35 (18.3) / 28 (23.0) / 25 (26.6)
Commission T-score (n, %) / n=191 / n=122 / N=94
< 60 / 173 (90.6) / 107 (87.7) / 84 (89.4) / 0.58 / 0.78 / 0.64
60-70 / 17 ( 8.9) / 13 (10.7) / 10 (10.6)
>70 / 1 ( 0.5) / 2 ( 1.6) / 0
Overall Cognitive Function
Full Scale IQ (mean, SD) / 94.0 (16.0) (n=189) / 97.8 (14.8) (n=116) / 93.6 (14.6) (n=91) / 0.034 / 0.85 / 0.042
Verbal comprehension (mean, SD) / 93.5 (13.9) (n=190) / 98.1 (14.7) (n=121) / 90.8 (16.7) (n=96) / 0.006 / 0.17 / <0.001
Performance/Perceptual reasoning (mean, SD) / 95.8 (15.2) (n=193) / 99.5 (14.5) (n=120) / 94.7 (14.6) (n=96) / 0.028 / 0.56 / 0.016
Processing speed (mean, SD) / 94.9 (16.7) (n=190) / 97.0 (15.4) (n=118) / 94.2 (15.0) (n=93) / 0.26 / 0.74 / 0.19

Supplementary Table e-2 Baseline Characteristics of Participants enrolled in Second Monotherapy

Name / Ethosuximide
(n=75) / Lamotrigine
(n=55) / Valproic Acid
(n=78) / Overall p value
Demographics and Anthropometrics
Age (years, mean, SD) / 7.6 (2.2) / 7.7 (2.2) / 7.6 (2.3) / 0.93
BMI (mean, SD) / 17.5 (2.9) / 17.3 (2.6) / 17.3 (2.7) / 0.85
BMI-Z (mean, SD) / 0.5 (1.1) / 0.4 (1.1) / 0.5 (0.9) / 0.94
Sex Male (n, %) / 37 (49.3) / 17 (30.9) / 30 (38.5) / 0.11
Hispanic ethnicity (number, %) / 12 (16.0) / 13 (23.6) / 22 (28.2) / 0.20
Race / 0.79
Black (n, %) / 8 (10.7) / 8 (14.5) / 11 (14.1)
White (number, %) / 62 (82.7) / 41 (74.5) / 62 (79.5)
Other (number, %) / 5 ( 6.7) / 6 (10.9) / 5 ( 6.4)
Continuous Performance Test
Confidence index (mean, SD) / n=66 / n=50 / n=71
Mean, SD / 55.2 (21.4) / 53.3 (23.4) / 54.7 (27.0) / 0.92
≥ 0.6 (n, %) / 21 (31.8) / 17 (34.0) / 27 (38.0) / 0.75
Omission T-score (n, %) / n=67 / n=52 / n=72
< 60 / 45 (67.2) / 34 (65.4) / 47 (65.3) / 0.95
60-70 / 11 (16.4) / 9 (17.3) / 10 (13.9)
>70 / 11 (16.4) / 9 (17.3) / 15 (20.8)
Commission T-score (n, %) / n=67 / n=52 / N=72
< 60 / 61 (91.0) / 47 (90.4) / 65 (90.3) / 0.70
60-70 / 6 ( 9.0) / 4 ( 7.7) / 7 ( 9.7)
>70 / 0 / 1 ( 1.9) / 0
Overall Cognitive Function
Full Scale IQ (mean, SD) / 92.1 (13.0) / 94.5 (18.1) / 95.4 (17.0) / 0.46
Verbal comprehension (mean, SD) / 92.6 (12.3) / 93.7 (15.2) / 94.3 (14.5) / 0.76
Performance/Perceptual reasoning (mean, SD) / 94.9 (13.8) / 96.6 (16.2) / 96.0 (15.8) / 0.82
Processing speed (mean, SD) / 93.5 (14.0) / 94.8 (19.7) / 96.4 (16.9) / 0.59

Supplementary Table e-3: Impact of first AED on Freedom From Failure for second AED (table shows number and percent free from failure among those who received each combination of first and second monotherapies):

Outcome at Week 16-20 Visit
Second monotherapy / Ethosuximide (N=75) / Lamotrigine (N=55) / Valproic Acid (N=78)
First Monotherapy / Lamotrigine / Valproic Acid / P-value / Ethosuximide / Valproic acid / P-value / Ethosuximide / Lamotrigine / P-value
2nd Therapy failed / 20 (43%) / 8 (29%) / 0.32 / 18 (67%) / 12 (43%) / 0.11 / 10 (34%) / 17 (35%) / 1.0
Freedom from failure on 2nd monotherapy / 27 (57%) / 20 (71%) / 9 (33%) / 16 (57%) / 19 (66%) / 32 (65%)
Outcome at Month 12 Visit
2nd Therapy failed / 23 (49%) / 9 (32%) / 0.23 / 20 (74%) / 15 (54%) / 0.16 / 15 (52%) / 25 (51%) / 1.0
Freedom from failure on 2nd monotherapy / 24 (51%) / 19 (68%) / 7 (26%) / 13 (46%) / 14 (48%) / 24 (49%)

Supplementary Table e-4 - Adverseeventsin5%ormoreofparticipantsinanytreatmentgroup(numbersshownasn(%))

/ Ethosuximide / Lamotrigine / Valproic acid / Total /
Adverse effect / Up to
16-20 weeks
(N=75) / In between
16-20 weeks
and month 12
(N=47) / Up to
month12
(N=75) / Up to
16-20 weeks
(N=55) / In between
16-20 weeks
and month 12
(N=25) / Up to
month12
(N=55) / Up to
16-20 weeks
(N=78) / In between
16-20 weeks
and month 12
(N=51) / Up to
month12
(N=78) / Up to
month 12
(N=208) /
General whole body / 25(33) / 9(19) / 32(43) / 8(15) / 2(8) / 9(16) / 16(21) / 10(20) / 20(26) / 61(29)
Fatigue / 14(19) / 1(2) / 15(20) / 3(5) / 0(0) / 3(5) / 8(10) / 4(8) / 12(15) / 30(14)
Headache / 7(9) / 0(0) / 7(9) / 2(4) / 1(4) / 3(5) / 4(5) / 3(6) / 6(8) / 16(8)
Infection, bacterial / 3(4) / 2(4) / 5(7) / 2(4) / 0(0) / 2(4) / 2(3) / 0(0) / 2(3) / 9(4)
Fever / 1(1) / 2(4) / 3(4) / 0(0) / 0(0) / 0(0) / 3(4) / 1(2) / 4(5) / 7(3)
Gastrointestinal / 19(25) / 5(11) / 24(32) / 5(9) / 4(16) / 7(13) / 17(22) / 7(14) / 21(27) / 52(25)
Nausea and/or vomiting / 7(9) / 0(0) / 7(9) / 4(7) / 1(4) / 5(9) / 3(4) / 1(2) / 4(5) / 16(8)
Stomach upset / 6(8) / 1(2) / 7(9) / 2(4) / 1(4) / 3(5) / 5(6) / 1(2) / 6(8) / 16(8)
Appetite increase / 4(5) / 1(2) / 5(7) / 0(0) / 1(4) / 1(2) / 8(10) / 1(2) / 8(10) / 14(7)
Appetite decrease / 7(9) / 0(0) / 7(9) / 0(0) / 0(0) / 0(0) / 2(3) / 2(4) / 4(5) / 11(5)
Weight increase / 1(1) / 0(0) / 1(1) / 1(2) / 2(8) / 2(4) / 3(4) / 2(4) / 4(5) / 7(3)
Neuro-behavioral-psychiatric / 26(35) / 4(9) / 30(40) / 16(29) / 3(12) / 17(31) / 23(29) / 6(12) / 26(33) / 73(35)
Hyperactivity / 5(7) / 0(0) / 5(7) / 6(11) / 1(4) / 7(13) / 8(10) / 2(4) / 10(13) / 22(11)
Attention problems / 6(8) / 2(4) / 8(11) / 5(9) / 1(4) / 6(11) / 5(6) / 2(4) / 6(8) / 20(10)
Concentration decrease / 5(7) / 1(2) / 6(8) / 3(5) / 1(4) / 4(7) / 4(5) / 2(4) / 5(6) / 15(7)
Hostility / 3(4) / 1(2) / 4(5) / 4(7) / 1(4) / 4(7) / 6(8) / 1(2) / 7(9) / 15(7)
Personality Change / 5(7) / 0(0) / 5(7) / 3(5) / 0(0) / 3(5) / 3(4) / 0(0) / 3(4) / 11(5)
Slow Process Speed / 5(7) / 1(2) / 6(8) / 1(2) / 1(4) / 2(4) / 2(3) / 2(4) / 3(4) / 11(5)
Sleep Problem / 5(7) / 0(0) / 5(7) / 3(5) / 1(4) / 4(7) / 1(1) / 0(0) / 1(1) / 10(5)
Memory Problem / 5(7) / 0(0) / 5(7) / 1(2) / 0(0) / 1(2) / 3(4) / 0(0) / 3(4) / 9(4)
Dizziness / 4(5) / 0(0) / 4(5) / 2(4) / 0(0) / 2(4) / 1(1) / 0(0) / 1(1) / 7(3)
Tremor / 4(5) / 0(0) / 4(5) / 2(4) / 0(0) / 2(4) / 0(0) / 1(2) / 1(1) / 7(3)
Apathy / 5(7) / 0(0) / 5(7) / 1(2) / 0(0) / 1(2) / 0(0) / 0(0) / 0(0) / 6(3)
Depression / 4(5) / 0(0) / 4(5) / 0(0) / 0(0) / 0(0) / 2(3) / 0(0) / 2(3) / 6(3)
Confusion / 5(7) / 0(0) / 5(7) / 0(0) / 0(0) / 0(0) / 0(0) / 0(0) / 0(0) / 5(2)
Skin / 3(4) / 0(0) / 3(4) / 3(5) / 1(4) / 3(5) / 6(8) / 5(10) / 9(12) / 15(7)
Hair Loss / 2(3) / 0(0) / 2(3) / 2(4) / 1(4) / 2(4) / 2(3) / 5(10) / 7(9) / 11(5)