Workshop 2014

Psoriasis E. Paul Scheidegger

Workshop 2014 Teil 1 Allgemeines, Neuigkeiten Teil 2 Therapie Topisch – Lichttherapie – Systemtherapie

Psoriasis Häufige polygen vererbte Krankheit

der Haut, Nägel, Schleimhaut und Gelenke mit Befall von besonderen Prädilektionsorten

Primäreffloreszenz: erythematosquamöse Plaque

Koebner Phänomen

Häufige vererbte Krankheit der Haut, Nägel, Schleimhaut und Gelenke

mit Befall von besonderen Prädilektionsorten

• 2% der Bevölkerung

• 150 000 Patienten in der Schweiz

Häufige vererbte Krankheit der Haut, Nägel, Schleimhaut und Gelenke

mit Befall von besonderen Prädilektionsorten

• Vererbungsmodus unklar aber familiäre Häufung

- 1 Elternteil betroffen Risiko 20%

- 2 Eltern betroffen Risiko 50 - 75%

vererbte Krankheit

0%

0.7%/-4% 12%

70% 20%

Häufige vererbte Krankheit der Haut, Nägel, Schleimhaut und Gelenke

mit Befall von besonderen Prädilektionsorten

Prädilektionsorte

Varianten

Varianten

Varianten

Varianten

Entstehung der Psoriasis: normale Haut

Zellteilung 18 T

Transitzeit 28 T

Entstehung der Psoriasis: kranke Haut

Zellteilung 18 auf 1.5 T Transitzeit 28 auf 3 T

Proliferation

Entstehung der Psoriasis: kranke Haut Verkürzte Transitzeit

Vermehrung der Zellen Abschuppung

Entstehung der Psoriasis: Entzündung

Entstehung der Psoriasis: Entzündung

Proliferation Entzündung

Entstehung der Psoriasis: Autoimmun

Proliferation

Entzündung

Psoriasis = Autoimmunerkrankung

Was bedeutet Autoimmun

Psoriasis = Autoimmunerkrankung

Zusammenfassung -  Autoimmunerkrankung -  Entzündung -  Proliferation

Workshop 2014 Teil 1 Neuigkeiten

Schweizerische Psoriasis und Vitiligo Gesellschaft (SPVG)

www.spvg.ch

Allgm. Informationen

Workshop 2014 Teil 1 Neuigkeiten in der Therapie

Biologicals neue topische Anwendungen Betesil Pflaster Clarelux Schaum Daivobet Gel Onypso NL / Onyster NS

Workshop 2014 Teil 2 Behandlungen Topisch – Lichttherapie – Systemtherapie

topisch

systemisch

Licht

Topische Therapie

Hautpflege

Jede Psoriasis muss gepflegt werden !

Topische Therapie

Hautpflege

Cortison

Vitamin D

andere

Wie wirkt topische Therapie

Hautpflege

Cortison

Vitamin D

Teer

Licht

Nicht ansteckend !!

Therapie = Schweregrad

Jede Psoriasis muss gepflegt werden !

Psoriasis = Autoimmunerkrankung

•  Calcipotriol •  Anti-proliferativ, •  anti-inflammatorisch •  keine Tachyphylaxie •  1-2x täglich •  auch intertriginös, Gesicht •  Kombination mit Salicylsäure, Steroide, UVB

Vitamin D Analoga

topisch

„Neue“ Topische Therapien

„Neue“ Topische Therapien

„Neue“ Topische Therapien

Licht

Lichttherapie

Ganzkörper

Lichtkamm

Lichtlaser

Hand- und Fussgeräte

systemisch

systemisch Steroide MTX, CyS Vit A, Fumarsre Biologicals

Vor allem bei schwerer Psoriasis !

systemisch

Steroide MTX, CyS Vit A, Fumarsre Biologicals

Rotationstherapie

systemisch

Mild

Mittelschwere

Schwer Systemtherapie • Cyclosporin A • MTX • Neotigason • Fumarsäure Phototherapie • UVB 311nm, PUVA Lokaltherapie • Vitamin D Analoga • Steroide • Cignolin

Stadienabhängig

Psoriasis Therapie: Zusammenfassung

Psoriasis Therapie: PASI

Psoriasis Therapie: Biologicals

„Biologicals“

" Monoklonale Antikörper

" Fusions-Proteine " Zytokine

Concept from: Grabbe S, Schwarz T. Immunol Today. 1998;19:37-43.

Psoriasis = Autoimmunerkrankung

Embrel Remicaid

Nomenclature of biologic therapies

●  Etanercept -cept = human receptor fusion protein

●  Infliximab -ximab = chimaeric monoclonal antibody

●  Adalimumab

●  Ustekinumab -umab = fully human monoclonal antibody

Adapted from: Johnston SL. J Clin Pathol. 2007;60(1):8-17.

Ustekinumab1 Etanercept2 Infliximab3 Adalimumab4

Type of biologic Fully human

IgG1κ monoclonal antibody

Human TNFR2/p75 Fc fusion protein

Chimaeric human-murine IgG1 monoclonal

antibody

Recombinant human

monoclonal antibody

Target IL-12/23 p40 TNF-α

TNF-β (Lymphotoxin)

TNF-α# TNF-α#

Mode of action Blocks

IL-12 and IL-23 activity

Blocks TNF activity

Blocks TNF-α activity

Blocks TNF-α activity

Approved biologic therapies for plaque psoriasis Comparison of structure and function

1. Ustekinumab - European Summary of Product Characteristics. Date: March 2012. 2. Etanercept - European Summary of Product Characteristics. Date: March 2012.

3. Infliximab - European Summary of Product Characteristics. Date: December 2011. 4. Adalimumab - European Summary of Product Characteristics. Date: February 2012.

Adalimumab

Structure ●  Fully human monoclonal antibody

Target ●  TNF-α

Presumed mechanism of action ●  Attenuates inflammatory action of TNF-α

by interfering with binding to cell-surface receptors

●  Apoptosis of TNF-α-positive macrophages and T cells

Human anti-TNF-α#

Adalimumab - European Summary of Product Characteristics. Date: April 2010.

Adalimumab Mechanism of action

Adalimumab - European Summary of Product Characteristics. Date: April 2010.

Transmembrane-bound TNF-α#

Soluble TNF-α#

Receptor-bound TNF-α#

TNF receptor

Macrophage or activated T cell

Target cell

Etanercept

Structure ● Human fusion protein composed

of TNF receptor type II (TNF-R p75) and human IgG1 Fc fragment

Target ●  TNF-α and TNF-β (lymphotoxin-α)

Presumed mechanism of action ● Attenuates inflammatory action

of TNF by interfering with binding to cell-surface receptors

Complement binding region

Fc

Human p75 TNF receptor

Etanercept - European Summary of Product Characteristics. Date: November 2009.

Etanercept Mechanism of action

Transmembrane-bound TNF#

Soluble TNF#

TNF receptor

Macrophage or activated T cell

Target cell

Etanercept - European Summary of Product Characteristics. Date: November 2009.

Infliximab

Structure ●  Chimeric monoclonal antibody with

murine (mouse) variable region and human IgG1 region

Target ●  TNF-α

Presumed mechanism of action ●  Attenuates inflammatory action of TNF-α

by interfering with binding to cell-surface receptors

●  Apoptosis of TNF-α-positive macrophages and T cells

Human IgG1 region

Anti-TNF-α#

Murine variable region

Infliximab - European Summary of Product Characteristics. Date: March 2010.

Infliximab Mechanism of action

Infliximab - European Summary of Product Characteristics. Date: March 2010.

Transmembrane-bound TNF-α#

Soluble TNF-α#

Receptor-bound TNF-α#

TNF receptor

Macrophage or activated T cell

Target cell

Stelara Ustekinumab Mechanism of action

Infliximab - European Summary of Product Characteristics. Date: March 2010.

Stelara Ustekinumab Usage

Infliximab - European Summary of Product Characteristics. Date: March 2010.

Approved biologic therapies for plaque psoriasis Comparison of dosing and administration

Ustekinumab1 Etanercept2 Infliximab3 Adalimumab4

Method of administration Subcutaneous Subcutaneous Intravenous

infusion Subcutaneous

Induction dose 45/90 mg at weeks 0 and 4 NO 5 mg/kg at

weeks 0, 2, 6 80 mg at

wk 0

Maintenance dose

45/90 mg every

12 weeks

25/50 mg once or twice

weekly (up to 24 weeks)

5 mg/kg every

8 weeks

40 mg every

other week

Self-administered YES YES NO YES

Weight-based dosing YES NO YES NO

1. Ustekinumab - European Summary of Product Characteristics. Date: March 2012. 2. Etanercept - European Summary of Product Characteristics. Date: March 2012.

3. Infliximab - European Summary of Product Characteristics. Date: December 2011. 4. Adalimumab - European Summary of Product Characteristics. Date: February 2012.

Biologic therapies Comparison of tolerability and safety*

Ustekinumab1 Etanercept2 Infliximab3 Adalimumab4

Infusion/injection/ allergic reactions YES YES YES YES Malignancies/ lymphoma/HSTCL !, - , - !, !, - !, !, !† !, !, !†

Anti-drug antibodies‡ 5% 7% 28% 8%

Neurological events - ! ! ! Haematologic reactions - ! ! !

HBV reactivation - ! ! ! Hepatobiliary events/jaundice - !

1. Ustekinumab - European Summary of Product Characteristics. Date: March 2012. 2. Etanercept - European Summary of Product Characteristics. Date: March 2012.

3. Infliximab - European Summary of Product Characteristics. Date: December 2011. 4. Adalimumab - European Summary of Product Characteristics. Date: February 2012.

*Based on Contraindications (section 4.3) and Warnings and Precautions (section 4.4) of the SmPCs. † HSTCL with infliximab or adalimumab was reported only in patients with Crohn’s disease or ulcerative colitis. ‡ In patients enrolled in clinical studies of plaque psoriasis.

Ustekinumab1 Upper respiratory tract infection, nasopharyngitis

Etanercept2 Infections (including upper respiratory tract infections, bronchitis, cystitis, skin infections), injection site reactions (including bleeding, reddening, itching, pain, swelling)

Infliximab3 Viral infection (including influenza, herpes virus infection), headache, upper respiratory tract infection, sinusitis, abdominal pain, nausea, infusion-related reaction, pain

Adalimumab4

Respiratory tract infections (including lower and upper respiratory tract infection, pneumonia, sinusitis, pharyngitis, nasopharyngitis and pneumonia herpes viral), leucopaenia (including neutropenia and agranulocytosis), anaemia, lipids increased, headache, abdominal pain, nausea and vomiting, elevated liver enzymes, rash (including exfoliative rash), musculoskeletal pain, injection site reaction (including injection site erythema)

1. Ustekinumab - European Summary of Product Characteristics. Date: March 2012. 2. Etanercept - European Summary of Product Characteristics. Date: March 2012.

3. Infliximab - European Summary of Product Characteristics. Date: December 2011. 4. Adalimumab - European Summary of Product Characteristics. Date: February 2012.

*Very common (≥1/10)

Biologic therapies Very common adverse events*

FDA 2012.

Psoriasis treatment in pregnancy FDA categorisation of drug risk to the foetus

Treatment FDA foetal risk category

Adalimumab B

Etanercept B

Infliximab B

Ustekinumab B

Methotrexate X

Ciclosporin C

Acitretin X

Note: non-biologics included for comparison

Biologics in pregnancy FDA categorisation of drug risk to the foetus

● The FDA categorizes medicines according potential risk to the foetus ‒ The categories are from "Category A" (safest) to "Category X" (known

danger – do not use) ● Adalimumab, etanercept, infliximab and ustekinumab are all

category B medicines ‒ Either animal-reproduction studies have not demonstrated a foetal risk but

there are no controlled studies in pregnant women, or ‒ Animal-reproduction studies have shown an adverse effect (other than a

decrease in fertility) that was not confirmed in controlled studies in women in the first trimester (and there is no evidence of a risk in later trimesters)

FDA 2012.

PASI 75 and PASI 90 responses for infliximab (week 10 data), etanercept, ustekinumab (week 12 data) and adalimumab (week 16 data)

Patie

nts

(%)

34

11

Etanercept1 25 mg

100

80

40

0

20

60

Etanercept1 50 mg

49

21

100

80

40

0

20

60

Infliximab2 5 mg/kg

80

57

100

80

40

0

20

60

Adalimumab3 40 mg

71

45

100

80

40

0

20

60

Ustekinumab4 45 mg

67

42

100

80

40

0

20

60

Ustekinumab4 90 mg

76

51

100

80

40

0

20

60

Approved biologic therapies for plaque psoriasis PASI 75 and PASI 90 responses

1. Papp KA, et al. Br J Dermatol. 2005; 152:1304-12. 2. Reich K, et al. Lancet. 2005; 366:1367-1374. 3. Menter A, et al. J Am Acad Dermatol. 2008; 58:106-115. 4. Papp K, et al. Lancet. 2008;371:1675-84.

Note: Not head-to-head comparisons. PASI 75 PASI 90

Individuelle Beratung

Allgm Verhaltensmassnahmen

- Alkoholgenuss

- Psoriasis-fördernde Medikamente

- Urlaubsberatung „Klimatherapie“