A major new international research initiative

A major new international research initiative

Martin J Brodie

on behalf of the EUCARE Management Group

Presented by

EUCARE is a joint initiative of the ILAE and IBE supported by an unrestricted educational grant from UCB Pharma

FONDE STUDY Health burden of epilepsy

Around 5-10% of people will have a seizure at some time in their lives, 30% of whom will go on to develop epilepsy

Thus 1% of the world’s population will have epilepsy at any given point in time, amounting to a total of 40 million

30-40% of people with epilepsy will have uncontrolled seizures accounting for over 80% of the overall cost

This represents 1% of the Global Burden of Disease (WHO) and is equivalent to - breast cancer in women - lung cancer in men

NEWLY DIAGNOSED EPILEPSYEpilepsy wheel of fortune

Vagal nerve stimulation

Surgery

Seizure-free

Intolerable side-effects

Refractory

EARLY IDENTIFICATION OF EARLY IDENTIFICATION OF REFRACTORY EPILEPSYREFRACTORY EPILEPSY

Patrick Kwan and Martin J BrodieEpilepsy Unit, University Department of Medicine & Therapeutics

Western Infirmary, Glasgow, Scotland

February 3, 2000; 342: 314-319

NEWLY DIAGNOSED EPILEPSY Outcomes from July 1982 to May 2003

(N=780)

Responder – seizure-free for a minimum of 12 months Immediate responder – no seizures after starting treatment Remission – no relapse after becoming seizure-free Relapse – controlled for at least one year then refractory Non-responder – never seizure-free for any 12 months MEDIAN AGE 29 YEARS (RANGE 9-93)

MEDIAN FOLLOW-UP 6.6 YEARS (RANGE 2-21)

NEWLY DIAGNOSED EPILEPSY

Categories of response to treatment (N=780)

Non-responders(35.4%)

Remission (59.2%)

Immediate responders

(31.4%)

Relapse (5.4%)

Responders (64.6%)

Mohanraj R, Brodie MJ. Eur J Neurol 2006; 13: 277-82

NEWLY DIAGNOSED EPILEPSY Remission rates according to age

0

20

40

60

80

100

n=59 n=131 n=99 n=87 n=71 n=56 n=51 n=36 n=34 n=35 n=31 n=19 n=29 n=23 n=11 n=810-14 15-19 20-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 70-74 75-79 80-84 85+

Percentage

Brodie MJ, Kwan P. Br Med J 2005;331:1317-22

Months on treatmentNumber relapsedNumber at risk

80

85

90

95

100

0 12 24 36 48 60 72 84 96 108 12042 54

36 313

40 217

42 96

14 479

0 504

10.4% 10.4% 8.0% 4.2%Risk of relapse (%) 12 8 4 2Years of follow up

% seizure free

KAPLAN-MEIR PLOT OF TIME TO RELAPSE

OUTCOMES BY NUMBER OF PRE-TREATMENT SEIZURES

1 2 3 - 5 6 - 10 11 – 20 >20

(n=28) (n=149) (n=212) (n=89) (n=69) (n=233)

Number of pre-treatment seizures

0

20

40

60

80

100

UncontrolledRelapseRemission

25% 24% 39% 34% 48% 55%

14 20 32 30 45 50 11 4

7 4

35

75 76 61 66 52 45

%

p = 0.024

OUTCOMES BY DURATION OF EPILEPSY PRIOR TO STARTING TREATMENT

UncontrolledRelapseRemission

Time from first seizure until starting treatment (years)

(n=440) (n=124) (n=105) (n=60) (n=51)

0

20

40

60

80

100

< 1 1 - 2 3 - 5 6 - 10 > 10

38% 43% 45% 47% 45%

33 38 40 39 40

62 57 55 53 55

55 5 58

%

OUTCOMES BY NUMBER OF PRE-TREATMENT SEIZURES Three months before starting treatment

RelapseRemission

0

20

40

60

80

100

%

Uncontrolled

none 1 2 – 5 6 – 10 11 – 20 >20 (n=3) (n=164) (n=335) (n=64) (n=53) (n=64)

Number of pre-treatment seizures

0% 28% 38% 48% 49% 64%

21 32 48 45 61

100 72 62 52 51 36

7

6

4

3p < 0.001

NEWLY DIAGNOSED EPILEPSY

Predictors of refractoriness (multivariate analysis)

Odds ratio 95% CI p value

Family history 1.89 1.15-3.00 0.011

Febrile seizures 3.36 1.58-7.18 0.002

Traumatic brain injury 3.26 1.59-4.69 <0.001

Psychiatric comorbidity 2.17 1.33-3.55 0.002

Recreational drug use 4.26 2.03-8.94 <0.001

10 or more seizures 2.77 1.98-3.89 <0.001

Hitiris N et al. Epilepsy Research 2007; 75: 192-6

NEWLY DIAGNOSED EPILEPSY

Predictors of refractoriness (multivariate analysis)

Odds ratio 95% CI p value

Family history 1.89 1.15-3.00 0.011

Febrile seizures 3.36 1.58-7.18 0.002

Traumatic brain injury 3.26 1.59-4.69 <0.001

Psychiatric comorbidity 2.17 1.33-3.55 0.002

Recreational drug use 4.26 2.03-8.94 <0.001

10 or more seizures 2.77 1.98-3.89 <0.001

Hitiris N et al. Epilepsy Research 2007; 75: 192-6

NEWLY DIAGNOSED EPILEPSY Follow up of 97 consecutive patients undergoing

antero-temporal lobectomy

A lifetime history of depression was the sole predictor of post-surgical auras (p<0.0001) in seizure-free patients

A lifetime history of depression was also a predictor of disabling seizures with or without auras (p=0.001).

Kanner AM et al, Neurology, submitted

EPILEPSY MORTALITY

N SMR 95% CI p value

Newly diagnosed 890 1.42 1.16-1.72 p=0.0007

Chronic epilepsy 2689 2.05 1.83-2.26 p<0.0001

Mohanraj R et al Lancet Neurology 2006; 5: 481-7

No increase in risk was observed in patients who were seizure-free

0

20

40

60

80

100

Idiopathic Cryptogenic Symptomatic

UncontrolledRelapseRemission

34% 43% 44%

66 57 56

7 5

5

(N=222) (N=314) (N=244)

%

27 38 39

* + +

* p = 0.041

+ p = 0.035

*

Mohanraj R, Brodie MJ. Eur J Neurol 2006;13:277-82

NEWLY DIAGNOSED EPILEPSY Outcomes by syndromic classification

NEWLY DIAGNOSED EPILEPSY

Interictal EEG of a patient with juvenile myoclonic epilepsy showing generalised multiple spike-and-wave complexes

Mohanraj R, Brodie MJ. Acta Neurol Scand 2007; 115: 204-8

NEWLY DIAGNOSED EPILEPSY Treatment response in juvenile myoclonic epilepsies

(N=55; 25% population)

Non-responders(20%)

Remission (73%)

Immediate responders

(36%)

Relapse (7%)

Responders (70%)