Neuromodulation

MIGRAINE

FIRST LINE TREATMENT FOR MIGRAINE

Neuromodulation

MIGRAINE

FIRST LINE TREATMENT FOR MIGRAINE

MIGRÄN

FÖRSTAHANDSBEHANDLING MOT MIGRÄN

Neuromodulation

MIGRAINE TREATMENTCefaly®: The unique FDA approved device for migraine prevention

e-TNS: External Trigeminal Nerve StimulationThe Cefaly device is a transcutaneous nerve stimulator that is applied to the forehead (Fig. 1A) using a self-adhesive electrode positioned bilaterally over the upper branches of the trigeminal nerve (Fig. 1B). Cefaly is intended to stimulate the upper branches of the trigeminal nerve in order to reduce the fre-quency of migraine attacks.

e-TNS: Superhighway to the brain - Central action (4)

A sedative effect has been demonstrated by a randomized crossover sham-controlled trial (2). The central action has been confirmed by PET scan in a controlled trial (7) and by somatosensory evoked potentials (9).

1A 1B

MIGRÄNBEHANDLINGCefaly®: En unik FDA godkänd utrustning för migränprevention

e-TNS: Extern Trigeminal Nerv StimuleringCefaly är en transkutan nervstimulator som appliceras på pannan (Fig. 1A) med användning av en självhäftande elektrod positionerad bilateralt över de övre grenarna av trigeminusnerven (Fig. 1B). Cefaly är avsedd att stimulera de övre grenarna av trigeminusnerven för att minska frekvensen av migränanfall.

e-TNS: Motorvägen till hjärnan - Central åtgärd4

En sedatie effekt har visats genom en randomiserad crossover sham-kontrollerad studie 2. Den centrala verkan har bekräftats av PET-undersökning i en kontrollerad studie7 och av soma-tosensoriskt framkallade potentialer9.

Efficacy: Double-blinded randomized, placebo-controlled trial (3)

Migraine days reduction Responder rate

Significant Outcomes Acute drug intake reduction (3)

AFTER 3 MONTHS

-3.0

-2.5

-2.0

-1.5

-1.0

-0.5

0.0

0.5

0 1 2 3 Months

Cefaly *

Placebo

12.1%

38.1%

Placebo Cefaly

*

* p < 0.05

Perc

enta

ge d

ecre

ase

at e

nd o

f tria

l

5

0

-5

-10

-15

-20

-25

-30

-35

-40

-25

-13

-19

-4

-32

-3

Migrainedays

Migraineattacks

Total headachedays

Verum

Sham* p < 0.05

*

*

*

+0.5%

-36.6%

-74.5%

Placebo

CefalyAll a

CefalyResponders b

*

**

* p < 0.05

** p < 0.01

Reduction in migraine days during 3 months of treat-ment compared to baseline

≥ 50% responder rate at the third month of treatment compared to baseline

% of decrease at 3 months compared to baseline (a) Cefaly All: includes all patients, i.e. responders and non-responders.

(b) Cefaly Responders: patients who experience ≥ 50% reduction in migraine days.

Safety: Prospective study on 2,313 patients (5)

Cefaly® has reported side effects of only 4.3% in patients (all minor and fully reversible) vs. 50% (avg.) for typical oral preventive migraine medication.

Efficacy: Double-blinded randomized, placebo-controlled trial (3)

Migraine days reduction Responder rate

Significant Outcomes Acute drug intake reduction (3)

AFTER 3 MONTHS

-3.0

-2.5

-2.0

-1.5

-1.0

-0.5

0.0

0.5

0 1 2 3 Months

Cefaly *

Placebo

12.1%

38.1%

Placebo Cefaly

*

* p < 0.05

Perc

enta

ge d

ecre

ase

at e

nd o

f tria

l

5

0

-5

-10

-15

-20

-25

-30

-35

-40

-25

-13

-19

-4

-32

-3

Migrainedays

Migraineattacks

Total headachedays

Verum

Sham* p < 0.05

*

*

*

+0.5%

-36.6%

-74.5%

Placebo

CefalyAll a

CefalyResponders b

*

**

* p < 0.05

** p < 0.01

Reduction in migraine days during 3 months of treat-ment compared to baseline

≥ 50% responder rate at the third month of treatment compared to baseline

% of decrease at 3 months compared to baseline (a) Cefaly All: includes all patients, i.e. responders and non-responders.

(b) Cefaly Responders: patients who experience ≥ 50% reduction in migraine days.

Safety: Prospective study on 2,313 patients (5)

Cefaly® has reported side effects of only 4.3% in patients (all minor and fully reversible) vs. 50% (avg.) for typical oral preventive migraine medication.

Efficacy: Double-blinded randomized, placebo-controlled trial (3)

Migraine days reduction Responder rate

Significant Outcomes Acute drug intake reduction (3)

AFTER 3 MONTHS

-3.0

-2.5

-2.0

-1.5

-1.0

-0.5

0.0

0.5

0 1 2 3 Months

Cefaly *

Placebo

12.1%

38.1%

Placebo Cefaly

*

* p < 0.05

Perc

enta

ge d

ecre

ase

at e

nd o

f tria

l

5

0

-5

-10

-15

-20

-25

-30

-35

-40

-25

-13

-19

-4

-32

-3

Migrainedays

Migraineattacks

Total headachedays

Verum

Sham* p < 0.05

*

*

*

+0.5%

-36.6%

-74.5%

Placebo

CefalyAll a

CefalyResponders b

*

**

* p < 0.05

** p < 0.01

Reduction in migraine days during 3 months of treat-ment compared to baseline

≥ 50% responder rate at the third month of treatment compared to baseline

% of decrease at 3 months compared to baseline (a) Cefaly All: includes all patients, i.e. responders and non-responders.

(b) Cefaly Responders: patients who experience ≥ 50% reduction in migraine days.

Safety: Prospective study on 2,313 patients (5)

Cefaly® has reported side effects of only 4.3% in patients (all minor and fully reversible) vs. 50% (avg.) for typical oral preventive migraine medication.

Efficacy: Double-blinded randomized, placebo-controlled trial (3)

Migraine days reduction Responder rate

Significant Outcomes Acute drug intake reduction (3)

AFTER 3 MONTHS

-3.0

-2.5

-2.0

-1.5

-1.0

-0.5

0.0

0.5

0 1 2 3 Months

Cefaly *

Placebo

12.1%

38.1%

Placebo Cefaly

*

* p < 0.05

Perc

enta

ge d

ecre

ase

at e

nd o

f tria

l

5

0

-5

-10

-15

-20

-25

-30

-35

-40

-25

-13

-19

-4

-32

-3

Migrainedays

Migraineattacks

Total headachedays

Verum

Sham* p < 0.05

*

*

*

+0.5%

-36.6%

-74.5%

Placebo

CefalyAll a

CefalyResponders b

*

**

* p < 0.05

** p < 0.01

Reduction in migraine days during 3 months of treat-ment compared to baseline

≥ 50% responder rate at the third month of treatment compared to baseline

% of decrease at 3 months compared to baseline (a) Cefaly All: includes all patients, i.e. responders and non-responders.

(b) Cefaly Responders: patients who experience ≥ 50% reduction in migraine days.

Safety: Prospective study on 2,313 patients (5)

Cefaly® has reported side effects of only 4.3% in patients (all minor and fully reversible) vs. 50% (avg.) for typical oral preventive migraine medication.

Effektivitet: Dubbelblind randomiserad, placebo-kontrollerad studie3

Reducering av migrändagar under 3 månader av behandling jämfört med baslinjen

% av minskning vid 3 månader jämfört med baslinjen

≥ 50% responderhastighet vid den tredje behandlingsmånaden jämfört med baslinjen

(a) Cefaly Alla: inkluderar alla patienter, i.e. responders och icke-responders.(b) Cefaly Responders: patienter som erfarit ≥ 50% reduktion av migrändagar.

Reducering av migrändagar

Signifikant utfall

Responderhastighet

Reduktion av akut läkemedelsintag3

EFTER 3 MÅNADER

Säkerhet: Prospektiv studie på 2,313 patienter5

Cefaly® har rapporterade biverkningar hos endast 4.3% av patienterna (alla lindriga och fullständigt reversibla) vs. 50% (i snitt) för typisk oral preventiv migränmedicinering.

Drug LY2951742 ALD403 TEV48125 AMG334 Cefaly Valproate Topiramate Propranolol Amitriptyline

NNT 4 4.7 3.2 5.9 3.8 4 3 4 4

NNH 20 20 ∞ NA ∞ 7-14 2-17 NA NA

NNT: number needed to treat; NNH: number needed to harm; NA: non applicable; ∞: NNH, same percentage of patients experienced any adverse event in both placebo and drug treated patients.

Cefaly US, Inc187 Danbury Road - Wilton, CT 06897, USA

Phone: (203) 309-5670 - Fax: (203) 889-9564

CEFALY TechnologyLIEGE Science Park

Rue Louis Plescia, 34 - 4102 Seraing - Belgium

Comparison with other treatments (10)

Best safety/efficacy ratio for Cefaly®

References:(1) Cephalalgia 2009: Gérardy, P.Y., Fabry, D., Fumal, A., Schoenen, J. (2009). A

pilot study on supraorbital surface electrotherapy in migraine. Cephalalgia, 29, 134.

(2) BMC Neurology 2011: Piquet, M., Balestra, C., Sava, S. L., & Schoenen, J. (2011). Supraorbital transcutaneous neurostimulation has sedative effects in healthy sub-jects. BMC Neurology, 11(1), 135.

(3) Neurology 2013: Schoenen, J., Vandersmissen, B., Jeangette, S., Herroelen, L., Van-denheede, M., Gérard, P., & Magis, D. (2013). Migraine prevention with a supraorbital transcutaneous stimulator: A randomized controlled trial. Neurology, 80(8), 697-704.

(4) Neurology 2013: Faught, E., & Tatum, W. (2013). Trigeminal stimulation A super-highway to the brain?. Neurology, 80(9), 780-781.

(5) Journal of Headache and Pain 2013: Magis, D., Sava, S., D’Elia, T. S., Baschi, R., & Schoenen, J. (2013). Safety and patients’ satisfaction of transcutaneous su-praorbital neurostimulation (t-SNS) with the Cefaly® device in headache treatment: a survey of 2,313 headache sufferers in the general population. The Journal of Headache and Pain, 14 (1):95.

(6) Journal of Headache and Pain 2015: Russo, A., Tessitore, A., Conte, F., Marcuccio, L., Giordano, A., & Tedeschi, G. (2015). Transcutaneous supraorbital neurostimulation in “de novo” patients with migraine without aura: the first Italian expe-rience. The Journal of Headache and Pain, 16(1):69

(7) IHS, Valencia Spain, May 2015 (Submitted for publication): D’Ostillo, K., Laureys, S., (2015). Cerebral FDG uptake changes after supraorbital transcutaneous electri-cal stimulation with the Cefaly device in patients with migraine.

(8) Pain and Therapy 2015: Riederer, F., Penning, S., & Schoenen, J. (2015).Transcu-taneous Supraorbital Nerve Stimulation (t-SNS) with the Cefaly® Device for Migraine Prevention: A Review of the Available Data. Pain and Therapy, 4(2), 135-147.

(9) Journal of Headache and Pain 2015: Di Lenola, D., et al (2015). Transcuta-neous supraorbital nerve stimulation enhances somatosensory thalamic activity in migraine between attacks: a central mechanism of clinical efficacy? The Journal of Headache and Pain, 16 (Suppl 1): A160.

(10) BMC Medicine 2015: Mitsikostas, D. D., & Rapoport, A. M. (2015). New players in the preventive treatment of migraine. BMC Medicine, 13(1), 279.

(11) PR Newswire 2016: Migraine Medical Device, Cefaly, Shows Better Long-Term Patient Compliance than Migraine Medication http://www.prnewswire.com/news-releases/migraine-medical-device-cefaly-shows-better-long-term-patient-compli-ance-than-migraine-medication-300199939.html

Long term patient complianceCollected data on 14,745 migraine patients who use the Cefaly® device for more than 3 months (between 4 and 19 months) reveals a long-term compliance of 72.4%; much better than for oral preventive migraine medication.

Efficacy for compliant patients (6)

12.1%

38.1%

75%

Placebo Cefaly CefalyCompliant

*

***

* p < 0.05

*** p < 0.001

Responder Rate≥ 50%

Drug LY2951742 ALD403 TEV48125 AMG334 Cefaly Valproate Topiramate Propranolol Amitriptyline

NNT 4 4.7 3.2 5.9 3.8 4 3 4 4

NNH 20 20 ∞ NA ∞ 7-14 2-17 NA NA

NNT: number needed to treat; NNH: number needed to harm; NA: non applicable; ∞: NNH, same percentage of patients experienced any adverse event in both placebo and drug treated patients.

Cefaly US, Inc187 Danbury Road - Wilton, CT 06897, USA

Phone: (203) 309-5670 - Fax: (203) 889-9564

CEFALY TechnologyLIEGE Science Park

Rue Louis Plescia, 34 - 4102 Seraing - Belgium

Comparison with other treatments (10)

Best safety/efficacy ratio for Cefaly®

References:(1) Cephalalgia 2009: Gérardy, P.Y., Fabry, D., Fumal, A., Schoenen, J. (2009). A

pilot study on supraorbital surface electrotherapy in migraine. Cephalalgia, 29, 134.

(2) BMC Neurology 2011: Piquet, M., Balestra, C., Sava, S. L., & Schoenen, J. (2011). Supraorbital transcutaneous neurostimulation has sedative effects in healthy sub-jects. BMC Neurology, 11(1), 135.

(3) Neurology 2013: Schoenen, J., Vandersmissen, B., Jeangette, S., Herroelen, L., Van-denheede, M., Gérard, P., & Magis, D. (2013). Migraine prevention with a supraorbital transcutaneous stimulator: A randomized controlled trial. Neurology, 80(8), 697-704.

(4) Neurology 2013: Faught, E., & Tatum, W. (2013). Trigeminal stimulation A super-highway to the brain?. Neurology, 80(9), 780-781.

(5) Journal of Headache and Pain 2013: Magis, D., Sava, S., D’Elia, T. S., Baschi, R., & Schoenen, J. (2013). Safety and patients’ satisfaction of transcutaneous su-praorbital neurostimulation (t-SNS) with the Cefaly® device in headache treatment: a survey of 2,313 headache sufferers in the general population. The Journal of Headache and Pain, 14 (1):95.

(6) Journal of Headache and Pain 2015: Russo, A., Tessitore, A., Conte, F., Marcuccio, L., Giordano, A., & Tedeschi, G. (2015). Transcutaneous supraorbital neurostimulation in “de novo” patients with migraine without aura: the first Italian expe-rience. The Journal of Headache and Pain, 16(1):69

(7) IHS, Valencia Spain, May 2015 (Submitted for publication): D’Ostillo, K., Laureys, S., (2015). Cerebral FDG uptake changes after supraorbital transcutaneous electri-cal stimulation with the Cefaly device in patients with migraine.

(8) Pain and Therapy 2015: Riederer, F., Penning, S., & Schoenen, J. (2015).Transcu-taneous Supraorbital Nerve Stimulation (t-SNS) with the Cefaly® Device for Migraine Prevention: A Review of the Available Data. Pain and Therapy, 4(2), 135-147.

(9) Journal of Headache and Pain 2015: Di Lenola, D., et al (2015). Transcuta-neous supraorbital nerve stimulation enhances somatosensory thalamic activity in migraine between attacks: a central mechanism of clinical efficacy? The Journal of Headache and Pain, 16 (Suppl 1): A160.

(10) BMC Medicine 2015: Mitsikostas, D. D., & Rapoport, A. M. (2015). New players in the preventive treatment of migraine. BMC Medicine, 13(1), 279.

(11) PR Newswire 2016: Migraine Medical Device, Cefaly, Shows Better Long-Term Patient Compliance than Migraine Medication http://www.prnewswire.com/news-releases/migraine-medical-device-cefaly-shows-better-long-term-patient-compli-ance-than-migraine-medication-300199939.html

Long term patient complianceCollected data on 14,745 migraine patients who use the Cefaly® device for more than 3 months (between 4 and 19 months) reveals a long-term compliance of 72.4%; much better than for oral preventive migraine medication.

Efficacy for compliant patients (6)

12.1%

38.1%

75%

Placebo Cefaly CefalyCompliant

*

***

* p < 0.05

*** p < 0.001

Responder Rate≥ 50%

Drug LY2951742 ALD403 TEV48125 AMG334 Cefaly Valproate Topiramate Propranolol Amitriptyline

NNT 4 4.7 3.2 5.9 3.8 4 3 4 4

NNH 20 20 ∞ NA ∞ 7-14 2-17 NA NA

NNT: number needed to treat; NNH: number needed to harm; NA: non applicable; ∞: NNH, same percentage of patients experienced any adverse event in both placebo and drug treated patients.

Cefaly US, Inc187 Danbury Road - Wilton, CT 06897, USA

Phone: (203) 309-5670 - Fax: (203) 889-9564

CEFALY TechnologyLIEGE Science Park

Rue Louis Plescia, 34 - 4102 Seraing - Belgium

Comparison with other treatments (10)

Best safety/efficacy ratio for Cefaly®

References:(1) Cephalalgia 2009: Gérardy, P.Y., Fabry, D., Fumal, A., Schoenen, J. (2009). A

pilot study on supraorbital surface electrotherapy in migraine. Cephalalgia, 29, 134.

(2) BMC Neurology 2011: Piquet, M., Balestra, C., Sava, S. L., & Schoenen, J. (2011). Supraorbital transcutaneous neurostimulation has sedative effects in healthy sub-jects. BMC Neurology, 11(1), 135.

(3) Neurology 2013: Schoenen, J., Vandersmissen, B., Jeangette, S., Herroelen, L., Van-denheede, M., Gérard, P., & Magis, D. (2013). Migraine prevention with a supraorbital transcutaneous stimulator: A randomized controlled trial. Neurology, 80(8), 697-704.

(4) Neurology 2013: Faught, E., & Tatum, W. (2013). Trigeminal stimulation A super-highway to the brain?. Neurology, 80(9), 780-781.

(5) Journal of Headache and Pain 2013: Magis, D., Sava, S., D’Elia, T. S., Baschi, R., & Schoenen, J. (2013). Safety and patients’ satisfaction of transcutaneous su-praorbital neurostimulation (t-SNS) with the Cefaly® device in headache treatment: a survey of 2,313 headache sufferers in the general population. The Journal of Headache and Pain, 14 (1):95.

(6) Journal of Headache and Pain 2015: Russo, A., Tessitore, A., Conte, F., Marcuccio, L., Giordano, A., & Tedeschi, G. (2015). Transcutaneous supraorbital neurostimulation in “de novo” patients with migraine without aura: the first Italian expe-rience. The Journal of Headache and Pain, 16(1):69

(7) IHS, Valencia Spain, May 2015 (Submitted for publication): D’Ostillo, K., Laureys, S., (2015). Cerebral FDG uptake changes after supraorbital transcutaneous electri-cal stimulation with the Cefaly device in patients with migraine.

(8) Pain and Therapy 2015: Riederer, F., Penning, S., & Schoenen, J. (2015).Transcu-taneous Supraorbital Nerve Stimulation (t-SNS) with the Cefaly® Device for Migraine Prevention: A Review of the Available Data. Pain and Therapy, 4(2), 135-147.

(9) Journal of Headache and Pain 2015: Di Lenola, D., et al (2015). Transcuta-neous supraorbital nerve stimulation enhances somatosensory thalamic activity in migraine between attacks: a central mechanism of clinical efficacy? The Journal of Headache and Pain, 16 (Suppl 1): A160.

(10) BMC Medicine 2015: Mitsikostas, D. D., & Rapoport, A. M. (2015). New players in the preventive treatment of migraine. BMC Medicine, 13(1), 279.

(11) PR Newswire 2016: Migraine Medical Device, Cefaly, Shows Better Long-Term Patient Compliance than Migraine Medication http://www.prnewswire.com/news-releases/migraine-medical-device-cefaly-shows-better-long-term-patient-compli-ance-than-migraine-medication-300199939.html

Long term patient complianceCollected data on 14,745 migraine patients who use the Cefaly® device for more than 3 months (between 4 and 19 months) reveals a long-term compliance of 72.4%; much better than for oral preventive migraine medication.

Efficacy for compliant patients (6)

12.1%

38.1%

75%

Placebo Cefaly CefalyCompliant

*

***

* p < 0.05

*** p < 0.001

Responder Rate≥ 50%

Effekt för kompatibla patienter

Jämförelse med annan behandling10

Långsiktig patient complianceInsamlad data från 14,745 migränpatienter som använt Cefaly® utrustningen i mer än 3 månader (mel-lan 4 och 19 månader) visar en långsiktig compliance på 72.4%; mycket bättre än för oral förebyggande migränmedicinering.

Responderhastighet ≥ 50%

Bästa säkerjets-/effektförhållande för Cefaly

Timik AB, Sollentunavägen 63, 191 40 Sollentuna Tel: +46 (0) 8-35 15 00support@timik.sewww.timik.se