Challenges & approaches to Challenges & approaches to assess disease activity of assess disease activity of psoriasis and psoriatic psoriasis and psoriatic

arthritisarthritisGerald G Krueger MDGerald G Krueger MD

Professor, Benning Presidential Endowed ChairProfessor, Benning Presidential Endowed Chair

Dept of Dermatology University of UtahDept of Dermatology University of Utah

OMERACT / Malta 5/2006OMERACT / Malta 5/2006

pre-psoriasis to psoriasisT cell activation

A challenge: Ps / PsA (single vs multiple disorders)A challenge: Ps / PsA (single vs multiple disorders)

≈ 10 yrs

Composite photo of morphologic

variants of psoriasis

Composite photo of morphologic

variants of psoriatic arthritis

2.2. An Evolving Dogma “Psoriasis is a An Evolving Dogma “Psoriasis is a Complex Multigenic DiseaseComplex Multigenic Disease

A Further Challenge:Two Dogmas and Squaring of Same for

Ps and PsA

1. A Central Dogma DNA --> RNA --> Protein

Central Dogma : Genotype Dictates Phenotype

6p1p 5q31 16p 17q25

pre-psoriasis to psoriasisT cell activation

Psoriasis -- CMGDPsoriasis -- CMGD

Composite of photos of different morphologic forms of psoriasis

Central Dogma : Genotype Dictates Phenotype

6p1p 5q31 16p 17q25

pre-psoriasis to psoriasisT cell activation

Psoriatic arthritis -- CMGDPsoriatic arthritis -- CMGD

Composite of photos of different morphologic forms of psoriatic arthritis

Characterizing susceptibility to phenotypic variations of psoriasis by Characterizing susceptibility to phenotypic variations of psoriasis by comparing allelic association signals at comparing allelic association signals at PSORSPSORS loci loci; ; J. Panko, S. J. Panko, S. Schrodi, B. Wong, K. Callis, N. Matsunami, M. A. Cargill, G. G. Schrodi, B. Wong, K. Callis, N. Matsunami, M. A. Cargill, G. G. Krueger, University of Utah and Celera DiagnosticsKrueger, University of Utah and Celera Diagnostics [SID May 2006][SID May 2006]

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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

ConclusionConclusionPs & PsA Represent a Complex Ps & PsA Represent a Complex

Multigenic DiseaseMultigenic Disease

Genotype Dictates PhenotypeGenotype Dictates Phenotype

A Role, vs Just Dogma?A Role, vs Just Dogma?

Early Analysis Indicates a RoleEarly Analysis Indicates a Role

Assessment toolsAssessment tools

What do we haveWhat do we have

What do we wantWhat do we want

Tools to quantitate clinical improvement Tools to quantitate clinical improvement in psoriasis: in psoriasis: What we haveWhat we have

Clinical Assessments - SubjectiveClinical Assessments - Subjective PASIPASI PGA: PGA: DynamicDynamic + / - assisted recall; + / - assisted recall; StaticStatic OLAOLA National Psoriasis Foundation Psoriasis Score (NPF-PS)National Psoriasis Foundation Psoriasis Score (NPF-PS) Lattice System-Global Psoriasis Score (LS-GPS)Lattice System-Global Psoriasis Score (LS-GPS) Target lesions: + / - BSATarget lesions: + / - BSA QOL (SF36, DLQI, others)QOL (SF36, DLQI, others)

Clinical Assessments - Objective Clinical Assessments - Objective Biopsy -- thickness, biomarkers (real time PCR, EGIR, etc)Biopsy -- thickness, biomarkers (real time PCR, EGIR, etc) PhotographsPhotographs

PASIPASIE = ErythemaI = Infiltration (induration; thickness; elevation)D = Desquamation (scale; scaling)A = Score for % involvement in each body area

Fredriksson & Pettersson, Dermatologica 1978; 157:238

PASI problemsPASI problems Plaque qualities (e.g., induration) not definedPlaque qualities (e.g., induration) not defined Area is non-linear, uses a 1-6 scale (1 = <10% BSA, 2 = 10-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-<30% BSA, 3 = 30-<50% BSA, 4 = 50-<70% BSA, 5 = 70-<90% BSA, and 6 = 90-100% BSA)<90% BSA, and 6 = 90-100% BSA)

Erythema, induration, scaling all weighted equallyErythema, induration, scaling all weighted equally Plaque induration may be more importantPlaque induration may be more important

(FDA and investigator consensus)(FDA and investigator consensus) Small amount of disease = less reduction than appreciated Small amount of disease = less reduction than appreciated

clinicallyclinically Continuous, not in steps, PASI 50 and PASI 75 arbitrary Continuous, not in steps, PASI 50 and PASI 75 arbitrary

endpointsendpoints

PASI problems, cont’d / PASI problems, cont’d / butbut

Not intuitive to physicians or patientsNot intuitive to physicians or patients– 50% or 75% reduction in PASI -- what does this mean when 50% or 75% reduction in PASI -- what does this mean when

recognized that score is non-linear?recognized that score is non-linear? Clear/almost clear not definedClear/almost clear not defined ButBut

It works! [validated numerous times]It works! [validated numerous times] Is robust! [detects relatively small changes, Is robust! [detects relatively small changes,

significance with relatively small cohorts (depends significance with relatively small cohorts (depends on response)]on response)]

The NPF ScoreThe NPF Score

Primary End Points

Induration, Target Lesion A (0-5) 5

Induration, Target Lesion B (0-5) 5

BSA Current / Baseline (0-5) 5

Physician's Global Assessment (0-5) 5

Patient's Global Assessment (0-5) 5

Patient's Assessment of Itch (0-5) 5

Maximum Possible Score 30

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

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The optimal assessment tool for Ps & PsA The optimal assessment tool for Ps & PsA What we* wantWhat we* want

Broadly: an assessment tool that accurately and predictably Broadly: an assessment tool that accurately and predictably reflects disease activityreflects disease activity

Features of “the ideal assessment tool” Features of “the ideal assessment tool” Measures BSAMeasures BSA Measures EIS (erythema, induration & scale)Measures EIS (erythema, induration & scale) Brings quantification to PsABrings quantification to PsA Brings quantification to nail disease seen with PsBrings quantification to nail disease seen with Ps Assesses impact of Ps and it’s component elements on QOLAssesses impact of Ps and it’s component elements on QOL Assesses patient satisfaction with treatmentAssesses patient satisfaction with treatment Static, easy to use and clinically meaningful Static, easy to use and clinically meaningful

Frequently used to define severity of Ps

*IPC Jan 2006

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 # 1 Proposed patient satisfaction tool # 1

Proposed patient satisfaction tool # 2 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 youThank you

QuestionsQuestions