Outcome Measures in PsA Philip Mease MD Seattle, WA
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) * Clegg DO. Arthritis Rheum. 1996;39:2013.
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)
Prior RCTs in PsA *Psoriasis Area and Skin Index. ** Number of controlled studies
Bibliography of Key RCTs in PSA • 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. • 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. • 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. • 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. • 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. • 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).
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
Unique Elements of PsA Trials • Inclusion of oligoarticular patients • Allowance of other DMARD background in trials with biologics • Equal gender prevalence • Assessment of skin
Therapeutic Responses in PsA Effect on Joint Disease * 12 weeks; ** 16 weeks;***24 weeks
Mean Values >5.1 Non-responders <3.2 Good Response Mean DAS 28 Score 0 18 2 10 16 38 14 30 50 6 22 46 Week DAS28 Score Over Time
Enthesitis Over Time (IMPACT I) Number of Patients with Enthesitis *p=0.05 vs placebo
Dactylitis Score (IMPACT I) Dactylitis Score
Therapeutic Responses in PsA: HAQ Changes p value • Etanercept II 1.20 <.0001 • Etanercept III .54 <.0001 • Infliximab II .60 <.0001 • Leflunomide .19 .0267
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 VAS 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 Core Sets in PsA