Outcome Measures in PsA

Philip Mease MD

Seattle, WA

* 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)

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 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

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).

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

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

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

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

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

Therapeutic Responses in PsA: HAQ Changes

p value

• Etanercept II 1.20 <.0001

• Etanercept III .54 <.0001

• Infliximab II .60 <.0001

• Leflunomide .19 .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