psoriasis: therapeutic goals · – h) extensive erythroderma or pustular psoriasis; and – i)...
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Psoriasis: Therapeutic goals
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Efalizumab 6 doses: flare + REBOUND
impetiginization
“I want to die”
CSA 3
infliximab
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
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 - -- --
Infliximab 5 mg/kg1
Etanercept 50 mg BIW1
Adalimumab 40 mg EOW1
Cyclosporin 3 mg/kg/day1
Methotrexate 15-22.5 mg/w1
Ustekinumab 45 mg2,3
Ustekinumab 90 mg2,3
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.
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0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%
Probability of PASI75 Response to Treatment [95% CI] - Induction
Safety of systemic treatments for psoriasis CSA MTX Acitretin Fumarates PUVA
Teratogenicity Yes Yes
Carcinogenicity
Lymphoma EBV-associated
Skin cancer Yes Melanoma (RA) Yes
Solid carcinomas Lung (RA)
Immune suppression TBC, others Yes Yes
Organ toxicity/ comorbidities
Kidney, hypertension Yes
Liver ++ +
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 disease2
• > PASI 75 improvement as a minimum standard • Complete skin clearance as the ultimate goal
– Rapid control of psoriatic disease1
• Clearing nails3
• PsA3
– Sustained control in the long term1
• 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
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