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

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

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

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

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

6. p<0.001 p<0.01 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

7. ConclusionPs & 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. 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 = 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

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. 0.0 mm 0.25 mm Psoriasis Score 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 youQuestions