Transcript Outcome Measures in PsA

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
Compound
Sulfasalazine (5**)
Arthritis
Marginal
Skin
None
Methotrexate (1**)
Improvement in
Physician Global
Assessment only
Improvement
in area of skin
involvement only
Cyclosporine (abs.) Marginal
Good
Gold (1**)
Marginal
None
Azathioprine (1**)
Marginal
None
*Psoriasis Area and Skin Index.
** Number of controlled studies
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).
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
Trial
Etanercept1
ACR20
ACR50
ACR70
PsARC
Rx
P Rx
P Rx
P Rx
P
74% 14% 48% 5% 13% 0% 87%
23%
N=60*
Infliximab2
69%
8% 49% 9% 29% 0%
76.5%
18%
72%
31%
N=100**
Etanercept2
59% 15% 38% 4% 11% 0%
N=205*
Sulfasalazine3
N=221
Leflunomide 38.5% 20% NA
2
N=188***
* 12 weeks; ** 16 weeks;***24 weeks
57.8% 44.6
NA
NA
NA 57.9% 30%
DAS28 Score Over Time
Mean Values
6
Mean DAS 28 Score
>5.1 Non-responders
5
4
<3.2 Good Response
3
2
1
0
0 2
6
10
14 16 18
30
22
38
Week
Placebo
Infliximab
46
50
Enthesitis Over Time (IMPACT I)
Number of Patients with
Enthesitis
20
15
15*
13
13
10
7
5
3
4
0
Baseline
Week 16
Placebo
*p=0.05 vs placebo
Week 50
Infliximab
Dactylitis Score (IMPACT I)
Dactylitis Score
3.0
1.90
2.0
1.52
1.00
1.0
0.22
0.36
0.22
0.0
Baseline
Placebo
Week 16
Week 50
Infliximab
Therapeutic Responses in PsA: HAQ Changes
•
•
•
•
Etanercept II
Etanercept III
Infliximab II
Leflunomide
1.20
.54
.60
.19
p value
<.0001
<.0001
<.0001
.0267
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