1. Outcome Measures in PsA Philip Mease MD Seattle, WA

2. * Clegg DO. Arthritis Rheum. 1996;39:2013. Measures of PsA Outcome ACR Response Criteria: 20%, 50%, 70% (validated in RA, not PsA) –Tender and swollen joint count (modified for PsA to include DIP and CMC joints: 78/76) –3/5: patient global, physician global, patient pain, HAQ, acute phase reactant (sed rate, CRP) Psoriatic Arthritis Response Criteria (PsARC)* –Improvement in at least 2 of 4 criteria, including: –Physician global assessment (0-5) –Patient global assessment (0-5) –Tender joint score (>30%) –Swollen joint score (>30%) –Improvement in at least 1 of 2 joint scores –No worsening in any criteria Disease Activity Score (DAS)

3. Measures of PsA Outcome (cont.) Enthesitis score Dactylitis score Function/QOL/Disability Indices (HAQ, SF-36, DLQI, PsAQOL) Radiographic (Modified Sharp, Modified Steinbrocker, Wassenberg) (to be discussed by van der Heijde) Skin (PASI, target lesion, static global) (to be discussed by G Krueger)

4. Prior RCTs in PsA CompoundArthritisSkin Sulfasalazine (5**) Methotrexate (1**) Cyclosporine (abs.) Gold (1**) Azathioprine (1**) Marginal Improvement in Physician Global Assessment only Marginal None Improvement in area of skin involvement only Good None *Psoriasis Area and Skin Index. ** Number of controlled studies

5. Bibliography of Key RCTs in PSA 1.Antoni C, Kavanaugh A, Kirkham B, et al. The infliximab multinational psoriatic arthritis controlled trial (IMPACT): substantial efficacy on synovitis and psoriatic lesions with or without concomitant DMARD therapy. Arthritis Rheum 2002;46(9):S381. 2.Antoni C, Kavanaugh A, Kirkham B, Burmester G, et al. The One Year Results of the Infliximab Multinational Psoriatic Arthritis Controlled Trial (IMPACT): Substantial Efficacy on Synovitis and Psoriatic Lesions With or Without Concomitant DMARD Therapy. Arthritis Rheum 2003;48(9):S265. 3.Clegg DO, Reda DJ, Mejias E, et al. Comparison of sulfasalazine and placebo in the treatment of psoriatic arthritis. A Department of Veterans Affairs Cooperative Study. Arthritis Rheum 1996;39(12):2013-20. 4.Kaltwasser JP, Nash P, Gladman D, et al. Efficacy and safety of leflunomide in the treatment of psoriatic arthrits and psoriasis. Arthritis Rheum 2004;50(6):1939-50. 5.Mease PJ, Goffe BS, Metz J, VanderStoep A, Finck B, Burge DJ. Etanercept in the treatment of psoriatic arthritis and psoriasis: a randomised trial. Lancet 2000;356(9227):385-90. 6.Mease P, Kivitz A, Burch F, et al. Etanercept treatment of psoriatic arthritis: safety, efficacy, and effect on disease progression. Arthritis Rheum 2004;(in press July).

6. Pure PsA vs. Mixed SpA Trials Valuable data about PsA response to therapy discernable from mixed SpA trials Uncertainty about the validity of instruments such as the BASDAI in PsA if there is little or no spine involvement

7. Unique Elements of PsA Trials Inclusion of oligoarticular patients Allowance of other DMARD background in trials with biologics Equal gender prevalence Assessment of skin

8. Therapeutic Responses in PsA * 12 weeks; ** 16 weeks;***24 weeks Effect on Joint Disease

9. DAS28 Score Over Time Mean Values Mean DAS 28 Score <3.2 Good Response >5.1 Non-responders Week 2 6 14 16 22 30 38 46 50 0 10 18

10. Enthesitis Over Time (IMPACT I) Number of Patients with Enthesitis *p=0.05 vs placebo

11. Dactylitis Score (IMPACT I) Dactylitis Score

12. Therapeutic Responses in PsA: HAQ Changes p value Etanercept II1.20<.0001 Etanercept III.54<.0001 Infliximab II.60<.0001 Leflunomide.19.0267

13. Core Sets in PsA Domain –Joint assessment –Axial assessment* –Skin assessment –Pain –Patient global –Physician global –Function/QOL* –Fatigue* –Enthesial assessment* –Dactylitis assessment* –Stiffness –Acute phase reactants –Xray* –MRI* –Ultrasound* –Clinical subset response* * Needs development/validation Instrument –T/S joint count, ACR, PsARC, DAS* –? –PASI, Target lesion, Global –VAS –HAQ, SF-36, DLQI, PsAQOL –Krupp, MFI, FACIT, one question –Mander, MASES, present or absent –0-4 scale, Helliwell scale –Duration minutes –ESR, CRP –Sharp, Larsen, Steinbrocker –? –Need clear guidelines to define clinical subsets in order to assess subset response