Gerald G Krueger MD Professor, Benning Presidential Endowed Chair

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Presentation transcript:

Challenges & approaches to assess disease activity of psoriasis and psoriatic arthritis Gerald G Krueger MD Professor, Benning Presidential Endowed Chair Dept of Dermatology University of Utah OMERACT / Malta 5/2006

A challenge: Ps / PsA (single vs multiple disorders) T cell activation pre-psoriasis to psoriasis Composite photo of morphologic variants of psoriasis Composite photo of morphologic variants of psoriatic arthritis ≈ 10 yrs

An Evolving Dogma “Psoriasis is a Complex Multigenic Disease A Further Challenge: Two Dogmas and Squaring of Same for Ps and PsA A Central Dogma DNA --> RNA --> Protein An Evolving Dogma “Psoriasis is a Complex Multigenic Disease

Composite of photos of different morphologic forms of psoriasis Psoriasis -- CMGD T cell activation pre-psoriasis to psoriasis Central Dogma : Genotype Dictates Phenotype 1p 5q31 6p 16p 17q25 Composite of photos of different morphologic forms of psoriasis

Psoriatic arthritis -- CMGD Central Dogma : Genotype Dictates Phenotype 6p 1p 5q31 16p 17q25 pre-psoriasis to psoriasis T cell activation Composite of photos of different morphologic forms of psoriatic arthritis

Characterizing susceptibility to phenotypic variations of psoriasis by comparing allelic association signals at PSORS loci; J. Panko, S. Schrodi, B. Wong, K. Callis, N. Matsunami, M. A. Cargill, G. G. Krueger, University of Utah and Celera Diagnostics [SID May 2006] 26,000 SNP micro-array of 11,000 functional genes on 500 cases and controls in UPI using a pooling strategies, eg PsA +/-; thick vs thin plaque, BSA, age of onset etc, phenotype SNP associations analyzed by moving average p<0.001 p<0.01

Conclusion Ps & PsA Represent a Complex Multigenic Disease Genotype Dictates Phenotype A Role, vs Just Dogma? Early Analysis Indicates a Role

Assessment tools What do we have What do we want

Tools to quantitate clinical improvement in psoriasis: What we have Clinical Assessments - Subjective PASI PGA: Dynamic + / - assisted recall; Static OLA National Psoriasis Foundation Psoriasis Score (NPF-PS) Lattice System-Global Psoriasis Score (LS-GPS) Target lesions: + / - BSA QOL (SF36, DLQI, others) Clinical Assessments - Objective Biopsy -- thickness, biomarkers (real time PCR, EGIR, etc) Photographs

Fredriksson & Pettersson, Dermatologica 1978; 157:238 PASI E = Erythema I = Infiltration (induration; thickness; elevation) D = Desquamation (scale; scaling) A = Score for % involvement in each body area Fredriksson & Pettersson, Dermatologica 1978; 157:238

PASI problems Plaque qualities (e.g., induration) not defined Area is non-linear, uses a 1-6 scale (1 = <10% BSA, 2 = 10-<30% BSA, 3 = 30-<50% BSA, 4 = 50-<70% BSA, 5 = 70-<90% BSA, and 6 = 90-100% BSA) Erythema, induration, scaling all weighted equally Plaque induration may be more important (FDA and investigator consensus) Small amount of disease = less reduction than appreciated clinically Continuous, not in steps, PASI 50 and PASI 75 arbitrary endpoints

PASI problems, cont’d / but Not intuitive to physicians or patients 50% or 75% reduction in PASI -- what does this mean when recognized that score is non-linear? Clear/almost clear not defined But It works! [validated numerous times] Is robust! [detects relatively small changes, significance with relatively small cohorts (depends on response)]

The NPF Score

NPF-PS Features Correlates well to PASI Psoriasis Score 0.0 mm 0.25 mm 0.50 mm 0.75 mm 1.00 mm 1.25 mm NPF-PS Features Correlates well to PASI Correlates better than PASI to QOL Works with low BSA -- topicals & systemics = 1 scoring system Has dynamic PtGA anchors recall to worst ever Has patient input on defined pruritus Has defined PGA (static) Features induration of 2 target lesions -- Early change in induration = predicts outcome Assessment = easy & more consistent with induration tool

The optimal assessment tool for Ps & PsA What we* want Broadly: an assessment tool that accurately and predictably reflects disease activity Features of “the ideal assessment tool” Measures BSA Measures EIS (erythema, induration & scale) Brings quantification to PsA Brings quantification to nail disease seen with Ps Assesses impact of Ps and it’s component elements on QOL Assesses patient satisfaction with treatment Static, easy to use and clinically meaningful Frequently used to define severity of Ps *IPC Jan 2006

Proposed patient satisfaction tool # 1 Overall Assessment of Satisfaction (OAS) with the current treatment / medication The overall satisfaction for a treatment for psoriasis depends upon many factors, including: how effectively it relieves symptoms, treats and prevents disease, cost, how quickly it works, the type and severity of side effects, ease of use; time needed and convenience to take and or get the treatment and your confidence that the medication / treatment is good for you. Taking all of these into account rate your overall satisfaction with your current treatment. 0 = Completely satisfied 5 = Very dissatisfied

Proposed patient satisfaction tool # 2 An overall assessment of desired (what is hoped for) response to treatment Rate the amount of improvement needed to reach your desired response to treatment (i.e. the level at which you would not want any additional treatment) 0 = Psoriasis is at desired response; no additional treatment needed 5 = Large amount is needed to reach desired response

Thank you Questions