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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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