Psoriasis: Therapeutic goals

I want to die 50 45 impetiginization infliximab 600 40 35 30 400 25 20 15 200 10 5 0 22-ene 21-feb 23-mar 22-abr 22- may Efalizumab 6 doses: flare + REBOUND CSA 3 21-jun 21-jul 20-ago 19-sep 19-oct 18-nov 18-dic 17-ene 16-feb 18-mar 17-abr 17- may 16-jun 0

Dec 19th Jan 30th Then he told me the Catalan traffic police had refrained him when he was about to jump from a highway bridge, just before his first appointment at our Department

Life changed: Prevent cumulative life impairment

Definitions of Moderate to Severe Psoriasis Moderate to severe psoriasis (grade II): requires (or has previously required) systemic treatment (including conventional drugs, biologic agents, and photo(chemo)therapy) Systemic treatment is indicated in patients with psoriasis in the following situations: a) disease not controlled with topical treatment; b) extensive disease (BSA >5%-10%); c) PASI >10; d) rapid worsening; e) involvement of visible areas; f) functional impairment (palmoplantar or genital involvement); g) subjective perception of severity (DLQI >10); h) extensive erythroderma or pustular psoriasis; and i) disease associated with psoriatic joint disease Puig L, et al. Psoriasis Group of the Spanish Academy of Dermatology. Actas Dermosifilliogr 2009;100:277-8

Goals of Treatment for Moderate to Severe Psoriasis PASI 75 ( 75% improvement from baseline PASI), PASI<5, PGA 1, or DLQI<5 Ultimate goal (ideal outcome, sustained response) Sustained complete clearance (PGA = 0) or almost complete clearance (PGA = 1) OR A minimal localized area of affected skin that can be controlled with topical treatment (PGA = 2, PASI <5). Induction therapy (within 10 to 16 weeks) Optimal: PASI 90 response, or clearance (PGA = 0) or only minimal signs of disease (PGA = 1) Reasonable: PASI 75 response Puig L, et al. Psoriasis Group of the Spanish Academy of Dermatology. Actas Dermosifilliogr 2009;100:277-8

Criteria for Selection of Therapy Treatment Efficacy, safety, cost, convenience, speed of action, effect on arthritis, effects on comorbidities Patient Age, sex (reproduction), weight, comorbidities, associated medications (interactions) UV ACT MTX CSA antitnf antip40 Arthritis + ++ + Dyslipemia - - Liver - - Diabetes - Heart failure - Cancer - - -? -? Interactions - -- --

Probability of PASI75 Response to Treatment [95% CI] - Induction Infliximab 5 mg/kg 1 Etanercept 50 mg BIW 1 Adalimumab 40 mg EOW 1 Cyclosporin 3 mg/kg/day 1 Methotrexate 15-22.5 mg/w 1 Ustekinumab 45 mg 2,3 Ustekinumab 90 mg 2,3 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% 1Bansback N, et al. Dermatol. 2009;219:209-18. 2. Leonardi CL, et al. Lancet. 2008;371:1665-74. 3. Papp KA, et al. Lancet. 2008;371:1675-84.

Safety of systemic treatments for psoriasis CSA MTX Acitretin Fumarates PUVA Teratogenicity Yes Yes Carcinogenicity Lymphoma Skin cancer Yes EBVassociated Melanoma (RA) Yes Solid carcinomas Lung (RA) Immune suppression TBC, others Yes Yes Kidney, hypertension Yes Liver ++ + Organ toxicity/ comorbidities Other contraindications Lipids, diabetes mellitus, drugs BM, lung, drugs Mucocutaneous, lipids, MSK GI, lymphopenia Arthritis (improvement) +/- +

Biologics Set a New Treatment Standard for Psoriasis Maximise treatment efficacy. 1 Significant effect on disease 2 > PASI 75 improvement as a minimum standard Complete skin clearance as the ultimate goal Rapid control of psoriatic disease 1 Clearing nails 3 PsA 3 Sustained control in the long term 1 Maximise patient quality of life. 2 DLQI score approaching 0 as goal Minimise side effects and potential impact on comorbidities. 1 PASI=Psoriasis Area and Severity Index; DLQI=Dermatology Life Quality Index. 1. Pardasani AG et al. Am Fam Physician. 2000;61:725 733, 736. 2. Pathirana D et al. J Eur Acad Dermatol Venereol. 2009;23(suppl 2):1 70. 3. Langley RG et al. Dermatology. 2010;221(suppl 1):29 42.

Traditional systemic treatments in the age of biologics In routine clinical practice, 30% patients require combined treatment with biologics and conventional systemics To maximize therapeutic outcome Overlapping when switching to a biologic Bridging when there is risk of rapid relapse or rebound after withdrawal To hasten the start of improvement with slow-onset biologics To overcome stabilization of improvement or decrease in effectiveness To decrease immunogenicity, clearance of incidence of infusion reactions (infliximab) Combined treatment with methotrexate, nbuvb and acitretin can be useful to optimize the therapeutic results and control transient flares of psoriasis Combination of biologics with traditional systemic therapies for psoriasis is off-label