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: (Prevalence) - 2% " " - 4.6% . , 0.4%-0.7% . -: 120,000 2,000
: (Prevalence) , 20-30 50-60 : 27 29
: (Prevalence) : 0.5-1.1% 16 8-12.5 -
: (Prevalence)- 2/3 - 1/3 -- 5-8% ( ) : - 5% 5
: , NSAIDs, HIV () PR , , , , (Known Trigers):
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Impact of Psoriasis vs Other Diseases on Patient-Reported Physical OutcomesRapp SR, et al. J Am Acad Dermatol. 1999;41:401-407.Ware JE Jr, et al. SF-36 Health Survey Manual and Interpretation Guide. The Health Institute; 1993.S F - 3 6 H E A L T H S U R V E YLower scores reflect worse patient-reported outcomes.Physical Component Summary Score (n=317)SF-36 ScorePsoriasis41Hypertension44Myocardial InfarctionCongestive Heart Failure35Diabetes42Depression45Arthritis43Cancer454342Chronic Lung Disease
Impact of Psoriasis vs Other Diseases on Patient-Reported Mental OutcomesRapp SR, et al. J Am Acad Dermatol. 1999;41:401-407.S F - 3 6 H E A L T H S U R V E YLower scores reflect worse patient-reported outcomes.Mental Component Summary Score (n=317)60403020100SF-36 ScoreChronic Lung Disease44Diabetes52CancerDepression35Psoriasis49Hypertension52Congestive Heart Failure50Myocardial Infarction524946Arthritis50
How do personality systems interact in patients with psoriasis, atopic dermatitis and urticaria? Bahmer JA, Kuhl J, Bahmer FA. Acta Derm Venereol. 2007;87(4):317-24
' . - , .
Role of depression in quality of life for patients with psoriasis Schmitt JM, Ford DE, Dermatology. 2007;215(1):17-27
32% 16.5% !
Psoriasis has a major secondary impact on the lives of family members and partners A.M. Eghlileb, et al, Br J Dermatol 156;6:1245-1250, June 2007
70% 57% 55% 44% , 37% , 37% 8%
: . 1/3 , ? /
: D A :Climatotherapy UVBNB-UVBLaserPUVA :' ""'
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A 52-week safety study of a calcipotriol/betamethasone dipropionate two-compound product (Daivobet) in the treatment of psoriasis vulgaris.Kragballe K, et al. Br J Dermatol 2006; 154(6):1155-60634 , " 52 ' "
EventDaivobet only(52 wks)
n=207Daivobet/ Daivonex(alt. 4 wks)n=213Daivobet 4 wks/ Daivonex 48 wksn=206%%%Burning sensation184.108.40.206Erythema1.01.93.4Pruritus5.810.313.1Skin irritation0.02.83.4
EventDaivobet only(52 wks)n=207Daivobet/ Daivonex(alt. 4 wks; n=213)Daivobet 4 wks/ Daivonex 48 wks (n=206)n%n%n%Adrenal insufficiency00.000.010.5Cellulitis00.000.010.5Ecchymosis10.500.000.0Folliculitis20.910.500.0Furuncle00.020.900.0Hypertrichosis00.000.010.5Purpura10.500.010.5Rash, pustular00.010.500.0Skin atrophy41.910.521.0Skin depigmentation21.000.000.0Skin papilloma00.010.500.0Skin striae00.010.500.0Total # of adverse events1176Total # of pts (%)104.862.862.9
4 weeks between visitsAverage drug consumption=17.3g/week in the Daivobetarm
Daivobet/Calcipotriol (4/4 alt)
Mean amount used (g)
VisitDaivobetDaivobet/Calcipotriol (4/4 alt)Daivobet/Calcipotriol (4/48)
Daivobet/Calcipotriol (4/4 alt)
Mean amount used (g)
- " " " - " (%5
Disease severityAcute treatment:Daivobet ODTreatment of flare-up:Daivobet ODStabilisation and maintenance:Daivobet OD as requiredStabilisation and maintenance:Daivobet OD as required
: Mild1% HydrocortizoneMethylprednisolone
ModerateClobetasone butirate(Eumovate)Fluocinolone acetonide (Dermalar)Betamethasone valerate (Betacorten)Diflucortolon valerate cr. (Neriderm Cr.)Desonide 0.1% (Locatop Cr.)PotentDiflucortolon valerate ung. (Neriderm)Halcinonide (Halciderm)Fluocortolone valerate (Ultralan)Momethasone fluorate (Elocom)Fluticasone propionate (Cutivate)Very potentDiflucortolon valerate fatty oint (Neriderm) Betamethasone dipropionate (Dicorten) (Diprolene)Clobetasole dipropionate (Dermovate) ("", "")
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A () ZoracTazarotene 0.1% gel in the treatment of fingernail psoriasis: a double-blind, randomized, vehicle-controlled study Scher RK, Stiller M, Zhu YICutis. 2001 Nov;68(5):355-8.Links
tazarotene 0.1% gel can significantly reduce onycholysis (in occluded and nonoccluded nails) and pitting (in occluded nails) and is well tolerated in the treatment of nail psoriasis
Tazarotene 0.1% gel for psoriasis of the fingernails and toenails: an open, prospective study L.Bianchi et al, British Journal of Dermatology 2003; 149: 193227 12 ' 0.1%
Tazarotene 0.1% gel for psoriasis of the fingernails and toenails: an open, prospective study L.Bianchi et al, British Journal of Dermatology 2003; 149: 193227
UVB 290-320 nmPUVA 320-400 nmNB UVB 311 nmLaser 308nmLaser585nm
Bath PUVA and saltwater baths followed by UV-B phototherapy as treatments for psoriasis: a randomized controlled trialSchiener R et al Arch Dermatol. 2007 May;143(5):586-96 1241 , 4 , 4 , 8 UVB, PUVA , UVB (TW-UVB), UVB (SW-UVB) Bath Puva, UVB-SW - UVB UVB-TW
A Pragmatic Randomized Controlled Trial on the Effectiveness of Highly Concentrated Saline Spa Water Baths Followed by UVB Compared to UVB Only in Moderate to Severe Psoriasis.Brockow T, et al, J Altern Complement Med. 2007 Sep;13(7):725-32
The study indicates that HC-SSW-UVB are superior to routine UVB at the end of a 6-week treatment course
The percentage of patients achieving PASI 75 after 1 month and remission time after climatotherapy at the Dead Sea.Harari M, et al, Int J Dermatol. 2007 Oct;46(10):1087-1091.95.5% - PASI 4 100% PASI 50, 75.9% PASI 75 23.1 33.6
Copyright 2007 BMJ Publishing Group Ltd.Weatherhead, S. et al. BMJ 2007;334:1218-1220Treatment advice to be given before conceptionin patients with psoriasis
Anti neoplasticMethotrexateImmunosuppressiveCyclosporineMycophenolateCorticosteroidsMethotrexateMetabolic stabilizationRetinoidsNeotigasonTigasonRoaccutaneFumaric acid derivativesFumaderm , , , , , , , , , , , , ,
American Academy of Dermatology recommendations for liver biopsy in patients with psoriasis receiving long-term methotrexate1. In patients without risk factors for liver damage, perform first liver biopsy after cumulative dose of 10-15 g MTX 2. Provided no significant abnormalities are found, repeat liver biopsy after each additional 15 g MTX3. When cumulative dose > 40 g, perform biopsy after each additional 10 g MTX4. In patients with risk factors for liver damage, perform liver biopsy within 2-4 months of starting MTX and after each additional 05-10 g thereafter
Replacement of routine liver biopsy by procollagen III aminopeptide for monitoring patients with psoriasis receiving long-term methotrexate: a multicentre audit and health economic analysis.Chalmers, R.J.G., Kirby, B., Smith, A., Burrows, P., Little, R., Horan, M., Hextall, J.M., Smith, C.H., Klaber, M. & Rogers, S.British Journal of Dermatology 152 (3), 444-450.
Biochemical and biophysical assessment of MTX-induced liver fibrosis in psoriasis patients: Fibrotest predicts the presence and Fibroscans predicts the absence of signicant liver fibrosisMaartje A. M. Berends, et al, Liver International 2007 27;5:639-645
Fibrotest accurately predicted the presence of significant liver fibrosis while the Fibroscan accurately predicted the absence of significant liver fibrosis in MTX users.
Psoriasis Is a T-CellMediated DiseaseNonlesional SkinPsoriatic PlaqueT Cells Source: Krueger JG. J Am Acad Dermatol. 2002;46:1-23. Vast Majority of T Cells Are Memory T CellsT Cells
Th1 inflammatory cytokines releasedTh1 inflammatory cytokines down-regulatedStrategy 3: Inducing Immune DeviationStrategy 2: Inhibiting T-Cell ActivationInflammatory cytokines releasedInflammatory cytokines inhibitedStrategy 4: Inhibiting CytokinesSources: Singri P, West DP, Gordon KB. Arch Dermatol. 2002;138:657-663.Biologic Treatment StrategiesStrategy 1: Selectively Targeting Pathogenic T Cells
"" ""Biological therapies for psoriasis & psoriatic arthritisAgentAgent typeClinical stageInfliximab (Remicade)anti TNF mc-AbApproved for PsoApproved for PAAdalimumab (Humira)anti TNF mc-AbIn phase IV trial for PsoApproved for PAEtanercept (Enbrel)Soluble TNF receptorFDA & EMEA approved for PsoFDA & EMEA approved for PAEfalizumab (Raptiva)T-cell modulatorFDA & EMEA approved for PsoFailed in PAAlefacept (amevive)T-cell modulatorFDA & IMH approved for Pso - - With MTXIn phase II trial for PA
/ 12 'Cost-effectiveness of biologic treatments for psoriasis based on subjective and objective efficacy measures assessed over a 12-week treatment period. Nelson AA etal, J Am Acad Dermatol. 2007 Nov 7
" : - 50% PASI 50 ( )
, - PA - 12 '" 12000$
- 12 '. 12 '. ! 3 100 " , 3 50 " ! 4-6 , , "
A virus-like particle-based vaccine selectively targeting soluble TNF-alpha protects from arthritis without inducing reactivation of latent tuberculosis. Spohn G, et al, J Immunol. 2007 Jun 1;178(11):7450-7
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Adalimumab (D2E7)Fully Human1st Murine2nd Chimeric3rd Humanized510% Mouse ProteinHuman25% Mouse Protein100% Mouse ProteinInfliximab(Remicade)CDP571Adalimumab (HUMIRA, D2E7)Afelimomab (SEGARD) TNF- Monoclonal Antibodies
Chimeric monoclonal antibody including murine variable regions and human IgG1 constant regionsSpecifically binds TNF- (circulating, membrane & receptor bound) Approved only for RA & Crohns diseaseKnight DM, et al. Mol Immunol. 1993;30:1443-1453.Scallon B, et al. J Pharmacol Exp Ther. 2002;301:418-426.MurineHumanInfliximab = Remicade
- Proportion Responding (%)Placebo(n=51)Infliximab 3 mg/kg(n=98)Infliximab 5 mg/kg(n=99)**75% PASI Reduction at Week 10*P
Slow IV infusion & risk of infusion reactionsSerum sicknessPotential formation of neutralizing antibodiesTuberculin skin test required/Chest X-rayInfection in 39% of patients vs 26% placeboTuberculosis, invasive fungal infections, and other opportunistic infections (some fatal) observed
Remicade package insert. Centocor; 2002.Infliximab: Safety Concerns
- Cutaneous and Systemic VasculitisNeutropenia, Leukopenia, thrombocytopenia, pancytopeniaNeurologic Events (demyelinating diseases)Lymphoma (B Cell) (94 patients)Positive ANA, Anti-nDNA frequent47 Medwatch reports to the FDA of new/worsening CHF in pts
Remicade :3-5 " " 0, 2, 6, 12 4-12 - 10,000 15,000 - RA - PA. - FDA - PSO. Off Label
Human, recombinant IgG1 monoclonal antibody against TNFBinds to circulating and cell-bound TNFHalf-life of 1020 days in RA trialsFixes complementTNFAdalimumab (human IgG1)HUMIRA (adalimumab)
* p < 0.001 vs placeboPercent of patients******Adalimumab in Psoriasis: Phase IIPASI 50/75/90 Responses at Week 12
More painful injection site reactionsIncreased risk of lymphoma 10 lymphomas in 2,468 ptsAllergic Reactions in 1% of patientsAssociation with demyelinating diseasesHematologic abnormalities13 Cases of Tb in clinical trials
Humira: Safety Concerns
Humira : - RA ! 40 " MTX - Pso - PA, 4 '
Etanercept: A fully human soluble TNF receptor
Etanercept helps restore anatural TNF balanceEtanercapt is a soluble TNF receptor that competitively binds to soluble TNF to prevent activation of cell-surface receptorsTNF signalingEtanercept bound to circulating TNFCell surface receptors are not activated by TNF
Possible flare of demyelinating diseaseRisk of CHF Risk of Tb Flare with Anti-TNF agents? Risk of Sepsis? Risk of Lymphoma with Anti-TNF agents (more with Infliximab)Positive ANA in 11%Etanercept: Safety Concerns
Enbrel : - RA - PA " - Pso 25 " X 2 SC, X1 . " 50 " X 2 3 . MTX - Pso .
Onercept TNF 3 - Enbrel - Phase III FDA . Enbrel.A b o r t e d ! ! !
? . Lymphoma Rates Are Low but Increased in Patients With Psoriasis. Results From a Population-Based Cohort Study in the United Kingdom Joel M. Gelfand, MD, MSCE; Jesse Berlin, ScD; Abby Van Voorhees, MD; David J. Margolis, MD, PhD Arch Dermatol. 2003;139:1425-1429. 11/03 0.001% 1:350 (%0.00285) Pso 1:275 (0.00364%) - TNF
RAPTIVAs mechanism of action inhibitsT-cell activationT-cell trafficking to the dermis and epidermisT-cell reactivationKrueger JG. The immunologic basis for the treatment of psoriasis with new biologic agents. J Am Acad Dermatol. 2002;46:1-23.Singri P, West DP, Gordon KB. Biologic therapy for psoriasis: the new therapeutic frontier. Arch Dermatol. 2002;138:657-663.RAPTIVA Mechanism of Action
- 010203040506070PASI 75PASI 50Placebo (n=187)RAPTIVA 1 mg/kg/wk (n=369)RAPTIVA (efalizumab) package insert. South San Francisco, Calif: Genentech, Inc; October 2003.Percentage of patients4%14%59%*27%**P
- Sustained responses to RAPTIVA have been observed in uncontrolled, open-label extension treatment trials when patients received RAPTIVA without interruption for 6 monthsPatients and investigators were blinded to treatment durationRAPTIVA (efalizumab) package insert. South San Francisco, Calif: Genentech, Inc; October 2003.Data on file. South San Francisco, Calif: Genentech, Inc; October 2003.*P
41%Percentage of Patients Achieving PASI 75Month 305020703010 Maintenance Period
First 3 Months
52%Month 6Month 12Month 15Mont...