Case Studies in Psoriatic Arthritis

Christopher Ritchlin, MD, MPH

Professor of Medicine

Director, Translational Immunology Research Center

University of Rochester Medical Center

Rochester, NY

Case 1

The teen with psoriasis and psoriatic arthritis

History

• 17 yo female raised in Indonesia now living in the US referred for management of PsA.

• Diagnosed with psoriasis at age 12 and managed with topicals. One year later developed joint pain and swelling and started on MTX 20 mg per week continued to the present. She has persistent psoriasis and joint pain. C/O nausea and mouth sores. H/O generalized anxiety disorder

• On exam: Pleasant but anxious teen who has normal BMI and vitals. Psoriasis over 5% BSA and T, Sw 2nd, 3rd MCP, PIPs. X rays without erosions

• How would you proceed with this patient?

Anxiety and depression in psoriasis and psoriatic arthritis

• Challenges faced by a teen

– Social stigma

– Need for lab draws every 2 weeks

– Commitment to chronic medication

Depression and anxiety prevalent in PsA

C-S study 83 PsA and 199 RA pts 1. 22% PsA vs 25% RA but 37% PsA polyarthritis depressed and anxious 2. 10% PsA vs 34% RA on meds. 3. Body symptoms independent correlates of physical HRQOL in PsA 4. PsA pts more likely to attribute illness to psychological factors

Kotsis, K et al. Arthritis Care Res, May 2012

Psoriasis Center URMC Psoriasis Center

Followup 2 years later

• Patient has continued on MTX. Currently entering sophomore year at Cornell. Interested in switching to anti-TNF agent. Wants to drink socially and tired of persistent psoriasis, joint pain, nausea & fatigue and recurrent blood draws.

• On exam- psoriasis over 2% BSA and T, Sw, 2nd 3rd MCP and PIPs in the R hand. Remainder of exam normal.

• PPD strongly positive and IFN release assay negative. BCG was administered as an infant in Indonesia. She routinely travels back and forth between US and Indonesia. HIV neg.

• What is your next step?

Drug Regimens for LTBI

Drug Regimen Liver toxicity

Stop Drug %

INH 300/d X9 mo or 900 twice a week X 6 mo

3.8 3.7

RIF 600/d X 4 mo 0.7 2.1

RIF + INH 600 RIF/d + 300 INH/d X 3 mo ? 4.9

Rifapentine + INH 900 RIFA + 900 INH/wk X 3 mo 0.4 4.9*

Horsburgh CR et al, NEJM, April 2011 Sterling TR et al, NEJM, Dec 2011

Case #2

A 38 yo woman with psoriatic disease and UBOs

Case #2

38 yo WF who developed psoriasis 6 years ago. She had moderate plaques that did not respond to topicals. The psoriasis worsened and involved 40% BSA.

She then developed PsA of the peripheral joints. MTX was started but stopped due to increased LFTs in the setting of fatty liver.

She was started on etanercept and both the joints and skin responded. Recently, she noted a holocranial headache and numbness in the UEs.

Exam and Data

Exam Obese WF NAD Skin: plaques limited to the elbows MSK: fusion of the L 2-4 IP joints of the feet NEURO: no focal findings Data MRI: multiple enhancing demyelinating lesions CSF: normal EMGs/NCVs: normal The etanercept was stopped and she was treated with oral solumedrol 1 mg/kg and over 6 weeks her symptoms improved but the skin and joint disease returned after the steroid taper.

Case #2

How would you treat her skin and joint disease?

1. Resume etanercept

2. Adalimumab

3. MTX

4. LEF

5. Ustekinumab

6. Abatacept

Demyelinating disease and TNFi

19 pts with neuro events:

paresthesias, visual loss, ataxia, confusion temporally related to initiation of TNFi

Partial or complete resolution of neuro symptoms after TNFi discontinued.

One pt had symptoms return on rechallenge

Demyelinating lesions

Mohan N. Arthritis Rheum. 2001;44(12):2862

Fibrosis in psoriasis pts on MTX

169 liver bx in 71 Ps pts on MTX

1.0

0.9

0.8

0.7

0.6

0.5

0.4

0.3

0.2

0.1

0.0

Rosenberg P J Hepatology 2007;46(6):1111.

Cum

ula

tive P

roport

ion F

ibro

sis

(sta

ge 3

or

4)

0 2 4 6 8 10 12 14 16 18 20

Accumulated doses with methotrexate (g)

No Over-weight

Over-weight Diabetes

No Diabetes

Ustekinumab in PsA: Summit 1

• Phase III DBRPCT

• 409 PsA, 206 placebo

• 45 & 90 mg sc q12Wk

• DMARD failures

• 49% on MTX

Week 24

• Sig improvement in

dactylitis, enthesitis and

HAQ at Wk 24

• PASI75 = 60%

• AEs: 2 pts with

erythroderma and 1 CVA in

Rx group

• Radiographic data under

analysis

Ustekinumab effective for skin and MSK inflammation in PsA

23

9 2

42

25

12

50

28

14

0

20

40

60

80

100

ACR20 ACR50 ACR70

Perc

ent of

patie

nts

McInnes et al. EULAR 2012, Berlin

P<0.001

Ustekinumab is not effective for MS

Phase II RDBCT 249 pts with RRMS

Cumulative endpt was # gad enhancing MRI lesions at week 23

UST no decrease in primary endpoint and no exacerbation of demyelinating events.

Segal BM. Lancet Neurol 2008;7:796

Case #3

45 yo female with arthritis and psoriasis

45 y.o. female

Presents with pain and swelling in fingers & toes. She was diagnosed with psoriasis at 25 years of age. GP prescribed anti-inflammatories with mild benefit. She is a mother of 4 children and works fulltime as a shop

assistant.

Sister diagnosed with pulmonary TB x 1 yr previously, All family members screened for latent TB, however subject

declined.

Case 3

Before Wk 12 Post

Case 3

Case 3

Case 3

Case 3

Case 3

• What treatment would you consider next?

Therapeutic Options

• Corticosteroids (CS) alone

• CS + DMARD

• CS + DMARD + TNFi

• Other Biologics

MIPA: MTX is not a DMARD in PsA

• 6-month DBRCT of MTX 15 mg/wk vs

PBO

• 1° EP: PsARC

2° EPs: ACR20, DAS28, global

and skin scores

MTX PBO

Baseline 109 112

Completed 71 77

• No difference in SJC, TJC, CRP/ESR, PsARC, ACR20, DAS28 at 3 and 6 months

• Pt, MD global and skin scores significantly improved at 6 months (P=0.03, 0.02, 0.02)

Kingsley GH et al, Rheumatology 2012

OR with 95% CI for composite measures

PsARC

ACR20

DAS28

5.00 1.00 0.50 Log OR

Despite issues with study design, MTX does not have disease-remitting properties

Case 3

• Psoriasis

• + Synovitis DIPJ

• + Nail dystrophy

• + Dactylitis