1. 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

2. 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

3. 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

4. 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

5. 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

6. 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

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

8. Assessment tools
What do we have
What do we want

9. 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

10. 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

11. 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 = % 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

12. 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)]

13. The NPF Score

14. 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

15. 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

16. 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

17. 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

18. Thank you Questions