Workshop 2014 Psoriasis. E. Paul Scheidegger

Transkript

1 Workshop 2014 Psoriasis E. Paul Scheidegger

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

3 Psoriasis Häufige polygen vererbte Krankheit der Haut, Nägel, Schleimhaut und Gelenke mit Befall von besonderen Prädilektionsorten Primäreffloreszenz: erythematosquamöse Plaque

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7 Koebner Phänomen

8 Häufige vererbte Krankheit der Haut, Nägel, Schleimhaut und Gelenke mit Befall von besonderen Prädilektionsorten 2% der Bevölkerung Patienten in der Schweiz

9 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%

10 vererbte Krankheit 0% 0.7%/-4% 12% 70% 20%

11 Häufige vererbte Krankheit der Haut, Nägel, Schleimhaut und Gelenke mit Befall von besonderen Prädilektionsorten

12 Prädilektionsorte

13 Varianten

14 Varianten

15 Varianten

16 Varianten

17 Entstehung der Psoriasis: normale Haut Zellteilung 18 T Transitzeit 28 T

18 Entstehung der Psoriasis: kranke Haut Zellteilung 18 auf 1.5 T Transitzeit 28 auf 3 T Proliferation

19 Entstehung der Psoriasis: kranke Haut Verkürzte Transitzeit Vermehrung der Zellen Abschuppung

20 Entstehung der Psoriasis: Entzündung

21 Entstehung der Psoriasis: Entzündung Entzündung Proliferation

22 Entstehung der Psoriasis: Autoimmun Proliferation Entzündung Psoriasis = Autoimmunerkrankung

23 Was bedeutet Autoimmun Psoriasis = Autoimmunerkrankung

24 Zusammenfassung - Autoimmunerkrankung - Entzündung - Proliferation

25 Workshop 2014 Teil 1 Neuigkeiten

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32 Allgm. Informationen Schweizerische Psoriasis und Vitiligo Gesellschaft (SPVG)

33 Workshop 2014 Teil 1 Neuigkeiten in der Therapie Biologicals neue topische Anwendungen Betesil Pflaster Clarelux Schaum Daivobet Gel Onypso NL / Onyster NS

34 Workshop 2014 Teil 2 Behandlungen Topisch Lichttherapie Systemtherapie

35 topisch systemisch Licht

36 Topische Therapie

37 Hautpflege Jede Psoriasis muss gepflegt werden!

38 Topische Therapie Hautpflege Cortison Vitamin D andere

39 Wie wirkt topische Therapie Vitamin D Hautpflege Cortison Teer Licht

40 Nicht ansteckend!! Psoriasis = Autoimmunerkrankung Therapie = Schweregrad Jede Psoriasis muss gepflegt werden!

41 Vitamin D Analoga Calcipotriol Anti-proliferativ, anti-inflammatorisch keine Tachyphylaxie 1-2x täglich auch intertriginös, Gesicht topisch Kombination mit Salicylsäure, Steroide, UVB

42 Neue Topische Therapien

43 Neue Topische Therapien

44 Neue Topische Therapien

45 Licht

46 Lichttherapie Ganzkörper Hand- und Fussgeräte Lichtlaser Lichtkamm

47 systemisch

48 systemisch Steroide MTX, CyS Vit A, Fumarsre Biologicals Vor allem bei schwerer Psoriasis!

49 systemisch Rotationstherapie Steroide MTX, CyS Vit A, Fumarsre Biologicals

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51 Psoriasis Therapie: Zusammenfassung Stadienabhängig Systemtherapie Cyclosporin A MTX Neotigason Fumarsäure Phototherapie UVB 311nm, PUVA Lokaltherapie Vitamin D Analoga Steroide Cignolin Schwer Mittelschwere Mild

52 Psoriasis Therapie: PASI

53 Psoriasis Therapie: Biologicals

54 Biologicals " Monoklonale Antikörper " Fusions-Proteine " Zytokine

55 Psoriasis = Autoimmunerkrankung Embrel Remicaid Concept from: Grabbe S, Schwarz T. Immunol Today. 1998;19:37-43.

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58 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.

59 Approved biologic therapies for plaque psoriasis Comparison of structure and function Type of biologic Ustekinumab 1 Etanercept 2 Infliximab 3 Adalimumab 4 Fully human IgG1κ monoclonal antibody Human TNFR2/p75 Fc fusion protein Chimaeric humanmurine IgG1 monoclonal antibody Recombinant human monoclonal antibody TNF-α Target IL-12/23 p40 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 1. Ustekinumab - European Summary of Product Characteristics. Date: March Etanercept - European Summary of Product Characteristics. Date: March Infliximab - European Summary of Product Characteristics. Date: December Adalimumab - European Summary of Product Characteristics. Date: February 2012.

60 Adalimumab Human anti-tnf-α# 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 Adalimumab - European Summary of Product Characteristics. Date: April 2010.

61 Adalimumab Mechanism of action Macrophage or activated T cell Receptor-bound TNF-α# Soluble TNF-α# Transmembranebound TNF-α# TNF receptor Target cell Adalimumab - European Summary of Product Characteristics. Date: April 2010.

62 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 Human p75 TNF receptor Complement binding region F c Etanercept - European Summary of Product Characteristics. Date: November 2009.

63 Etanercept Mechanism of action Macrophage or activated T cell Transmembranebound TNF# Soluble TNF# TNF receptor Target cell Etanercept - European Summary of Product Characteristics. Date: November 2009.

64 Infliximab Structure Chimeric monoclonal antibody with murine (mouse) variable region and human IgG1 region Anti-TNF-α# Murine variable 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 Infliximab - European Summary of Product Characteristics. Date: March 2010.

65 Infliximab Mechanism of action Macrophage or activated T cell Receptor-bound TNF-α# Soluble TNF-α# Transmembranebound TNF-α# TNF receptor Target cell Infliximab - European Summary of Product Characteristics. Date: March 2010.

66 Stelara Ustekinumab Mechanism of action Infliximab - European Summary of Product Characteristics. Date: March 2010.

67 Stelara Ustekinumab Usage Infliximab - European Summary of Product Characteristics. Date: March 2010.

68 Approved biologic therapies for plaque psoriasis Comparison of dosing and administration Ustekinumab 1 Etanercept 2 Infliximab 3 Adalimumab 4 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 Etanercept - European Summary of Product Characteristics. Date: March Infliximab - European Summary of Product Characteristics. Date: December Adalimumab - European Summary of Product Characteristics. Date: February 2012.

69 Biologic therapies Comparison of tolerability and safety* Ustekinumab 1 Etanercept 2 Infliximab 3 Adalimumab 4 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 -! *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. 1. Ustekinumab - European Summary of Product Characteristics. Date: March Etanercept - European Summary of Product Characteristics. Date: March Infliximab - European Summary of Product Characteristics. Date: December Adalimumab - European Summary of Product Characteristics. Date: February 2012.

70 Biologic therapies Very common adverse events* Ustekinumab 1 Etanercept 2 Infliximab 3 Adalimumab 4 Upper respiratory tract infection, nasopharyngitis Infections (including upper respiratory tract infections, bronchitis, cystitis, skin infections), injection site reactions (including bleeding, reddening, itching, pain, swelling) Viral infection (including influenza, herpes virus infection), headache, upper respiratory tract infection, sinusitis, abdominal pain, nausea, infusion-related reaction, pain 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) *Very common ( 1/10) 1. Ustekinumab - European Summary of Product Characteristics. Date: March Etanercept - European Summary of Product Characteristics. Date: March Infliximab - European Summary of Product Characteristics. Date: December Adalimumab - European Summary of Product Characteristics. Date: February 2012.

71 Psoriasis treatment in pregnancy FDA categorisation of drug risk to the foetus Treatment Adalimumab Etanercept Infliximab Ustekinumab Methotrexate Ciclosporin Acitretin FDA foetal risk category B B B B X C X Note: non-biologics included for comparison FDA 2012.

72 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.

73 Approved biologic therapies for plaque psoriasis PASI 75 and PASI 90 responses PASI 75 and PASI 90 responses for infliximab (week 10 data), etanercept, ustekinumab (week 12 data) and adalimumab (week 16 data) Patients (%) Etanercept 1 25 mg 0 Etanercept 1 50 mg 0 Infliximab 2 5 mg/kg 0 Adalimumab 3 40 mg 0 Ustekinumab 4 45 mg 0 Ustekinumab 4 90 mg Note: Not head-to-head comparisons. PASI 75 PASI Papp KA, et al. Br J Dermatol. 2005; 152: Reich K, et al. Lancet. 2005; 366: Menter A, et al. J Am Acad Dermatol. 2008; 58: Papp K, et al. Lancet. 2008;371:

74 Individuelle Beratung

75 Allgm Verhaltensmassnahmen - Alkoholgenuss - Psoriasis-fördernde Medikamente - Urlaubsberatung Klimatherapie