Outcome Measures in PsA
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Outcome Measures in PsA
Philip Mease MD
Seattle, WA
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* 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)
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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)
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Prior RCTs in PsA
Compound Arthritis Skin
Sulfasalazine (5**)
Methotrexate (1**)
Cyclosporine (abs.)
Gold (1**)
Azathioprine (1**)
Marginal
Improvement in Physician Global Assessment only
Marginal
Marginal
Marginal
None
Improvement in area of skin involvement only
Good
None
None
*Psoriasis Area and Skin Index.
** Number of controlled studies
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Bibliography of Key RCTs in PSA1. 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).
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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
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Unique Elements of PsA Trials
• Inclusion of oligoarticular patients
• Allowance of other DMARD background in trials with biologics
• Equal gender prevalence
• Assessment of skin
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Therapeutic Responses in PsA
Trial ACR20 Rx P
ACR50 Rx P
ACR70 Rx P
PsARC Rx P
Etanercept1
N=60* 74% 14% 48% 5% 13% 0% 87% 23%
Infliximab2 N=100**
69% 8% 49% 9% 29% 0% 76.5% 18%
Etanercept2 N=205*
59% 15% 38% 4% 11% 0% 72% 31%
Sulfasalazine3 N=221
57.8% 44.6
Leflunomide N=188***2
38.5% 20% NA NA NA NA 57.9% 30%
* 12 weeks; ** 16 weeks;***24 weeks
Effect on Joint Disease
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DAS28 Score Over TimeMean Values
Mea
n D
AS
28
Sco
re
0
1
2
3
4
5
6
Placebo Infliximab
<3.2 Good Response
>5.1 Non-responders
Week 2 6 14 16 22 30 38 46 500 10 18
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Enthesitis Over Time (IMPACT I)
13
3
13
7
4
15*
0
5
10
15
20
Baseline Week 16 Week 50
Placebo Infliximab
Nu
mb
er o
f P
atie
nts
wit
h
En
thes
itis
*p=0.05 vs placebo
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Dactylitis Score (IMPACT I)
1.52
1.00
0.36
1.90
0.22 0.22
0.0
1.0
2.0
3.0
Baseline Week 16 Week 50
Placebo Infliximab
Dac
tyli
tis
Sco
re
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Therapeutic Responses in PsA: HAQ Changes
p value
• Etanercept II 1.20 <.0001
• Etanercept III .54 <.0001
• Infliximab II .60 <.0001
• Leflunomide .19 .0267
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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– 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