Toronto Western Hospital

Newer Treatment Strategies in the Management of Psoriatic Arthritis

Vinod Chandran MBBS MD DM PhDKrembil Research Institute, University Health Network,

Institute of Medical Science,Department of Medicine,

Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto

CANADA

Outline

Psoriatic arthritis- Definition Treatment goals Early diagnosis Assessment and treating to target Challenges and unmet needs

PeripheralSpondyloarthritis

Spectrum of Spondyloarthritis:Current Concept

AS

Axial Spondyloarthritis

PsA

ReA

Arthritis with IBD

Non-radiographicAxial SpA

UndifferentiatedPeripheral SpA

Raychaudhuri S, Deodhar A. J Autoimmunity 2014;48-49:128-33

Treatment Strategy: Definition

A careful plan or method of treatment for achieving a particular goal usually over a long period of time

Adapted from http://www.merriam-webster.com/dictionary/strategy

Psoriatic Arthritis: Treatment Goals

1. Improve quality of life and function2. Prevent joint damage3. Reduce excess mortality risk

Strategies

1. Early diagnosis2. Treating to target

Impact of Early Diagnosis and Treatment

Gladman DD, et al. Ann Rheum Dis 2011;70:2152-4.

Variable Relative Rate of damage progression P value

PsA duration (>2yrs vs. < 2 yrs) 1.38 0.01

Age 1.03 <0.0001Calendar time 0.77 0.0005

Baseline damage 1.03 0.001

DMARDs at baseline 1.33 0.03

Biologics on follow up 1.43 0.006

DMARDs on follow up 1.62 0.003

Diagnosis within 6m of symptoms vs. laterOutcome OR P value

Erosions 4.25 <0.001HAQ 2.20 0.004

Haroon M, et al. Ann Rheum Dis 2015;74:1045-50.

How Do We Identify PsA Early?

Onset of Psoriasis precedes PsA in 70% Onset of PsA precedes psoriasis in 15% Both detected simultaneously in 15%

Psoriasis is a ‘pre-arthritic’ condition Close follow-up of people with psoriasis

may lead to early diagnosis of PsA

Relationship Between Psoriasis and PsA

Unmet Need- Early Diagnosis Performance of Screening questionnaires

(PASQ, PEST, and ToPAS)

Sensitivity: 0.67 - 0.84 Specificity: 0.64 - 0.75 PPV: 0.43 - 0.60 NPV: 0.83 - 0.91

Mease PJ, et al. J Am Acad Dermatol 2014;71:649-55.Haroon M, et al. Ann Rheum Dis 2015;74:1045-50.

Mease PJ, et al. J Am Acad Dermatol 2014;71:649-55.

Psoriatic Arthritis: Assessment

Psoriatic Arthritis

Skin & Nails

Peripheral

ArthritisAxial

ArthritisEnthesit

isDactyliti

s

Ritchlin C, et al. Ann Rheum Dis 2009;68:1387-94

Com

orbidities

Prognostic Value of achieving MDA:Results from the Toronto Cohort

Sustained MDA (N=116)

Did not achieve MDA (N=200)

P value

Change in Damaged Joint Count

0.931 2.245 P<0.001

Proportion with progression

51 69 P<0.001

Coates et al. Arthritis Care Res (Hoboken) 2010;62:970-6.Arthritis Care & Research Volume 62, Issue 7, pages 965-969Arthritis Care & Research Volume 68, Issue 2, pages 267-274

• Post Hoc analyses of clinical trial data• Patients who achieve sustained MDA

have less damage progression

Group for Research and Assessment of Psoriasis and Psoriatic Arthritis 2015 Treatment Recommendations for Psoriatic Arthritis

Arthritis & RheumatologyVolume 68, Issue 5, pages 1060-1071, 23 MAR 2016 DOI: 10.1002/art.39573http://onlinelibrary.wiley.com/doi/10.1002/art.39573/full#art39573-fig-0001

Aim • To assess the impact of tight control of early PsA in a

randomised-controlled trial using a treat-to-target approach

Methods• Randomized, controlled, single-blind trial• Minimal disease activity assessed every 4 wks

Primary Outcome• ACR20 at 48 weeks

Coates LC, et al. BMC Musculoskelet Disord. 2013 21;14:101.

Intensive Management to Achieve Minimal Disease Activity*

(n = 101)

Standard Care per Treating Physician(n = 105)

Yr 1

*Minimal disease activity criteria: tender joint count ≤ 1; swollen joint count ≤ 1; PASI ≤ 1 or BSA ≤ 3;pt pain VAS ≤ 15; pt global activity VAS ≤ 20; HAQ ≤ 0.5; tender entheseal points ≤ 1.

DMARD-naive pts with early

(< 24 mos), active psoriatic arthritis

(N = 206)

15

TICOPA Trial: Tight Control vs Standard Carein Early PsA

TICOPA: Treatment Algorithm

Intensive Management Group

MTXStart at 15 mg/wk escalating to 25 mg/wk

at Wk 6

MTX and SSZEscalating to 1g BID at Wks 4-8, then to

40 mg/kg/day max

MTX and CyAIncreasing by 1 mg/kg/day every 4 wks

MTX and LEFInitially 10 mg/day

increasing to 20 mg/day at

Wk 4

MTX and CyAIncreasing by 1 mg/kg/day every 4 wks

MTX and LEFInitially 10 mg/day

increasing to 20 mg/day at

Wk 4

Standard Therapy Group

Standard therapy as per treating physician

1st-line anti-TNF therapy for 12 wks

2nd-line anti-TNF therapy for 12 wks

ContinueContinue

MDA

MDA

MDA MDA

MDANot MDA

Not MDANot MDA (≥ 3T/S Jts)

Not MDA (≥ 3T/S Jts)

Not MDA (< 3T/S Jts)

Not MDA (< 3T/S Jts)

OR

OR

16

Coates LC, et al. Lancet 2015;386:2489-98.

TICOPA: Prescribed Treatment at Wk 48

Leflunomide

Methotrexate

Sulfasalazine

Intensive Management Standard Care

Biologic

Combination DMARD

No treatment

100

90

80

70

60

50

40

30

20

10

0

37.0

22.8

29.3

6.5

7.6

12.0

55.4

14.1

17

Patients (%)

Coates LC, et al. Lancet 2015;386:2489-98.

TICOPA Trial ACR Responses

18

62%

51%

38%

45%

25%

17%

0%

10%

20%

30%

40%

50%

60%

70%

ACR20 ACR50 ACR70

Tight ControlStandard Care

P=0.0392

P=0.0081

P=0.0058

Coates LC, et al. Lancet 2015;386:2489-98.

TICOPA: More AEs withIntensive Management vs Standard Care

No deaths in either treatment armSafety Outcome Intensive Management Standard CareAny AE, n 622 249

Drug-related AEs, n (%) 423 (68.0) 179 (71.8)

Serious AEs, n (%) 25 8

Drug-related serious AEs, n 8 2

Common AEs, n Nausea Abnormal liver function test Upper respiratory tract infection

(common cold) Gastrointestinal upset Fatigue

5437

463533

3839

14138

19

Coates LC, et al. Lancet 2015;386:2489-98.

Psoriasis/PsA: Therapeutic Targets

Adapted from Sheane B, Chandran V. Expert Opin Investig Drugs 2014;23:1001-16.

Treating to Target in Routine Practice

1. Assess all Domains2. Define target

– MDA- 5/7 of following:

3. Identify active domain(s)4. Weigh pros and cons of treatment escalation5. Patient Preference

Patient Reported Physician Reportedpatient pain VAS ≤15 Tender joint count ≤1

patient global activity VAS ≤20 Swollen joint count ≤1HAQ ≤0.5 Tender entheseal points ≤1

PASI ≤1 or BSA ≤3

Challenges & Unmet Needs Accurate and reliable assessment of disease activity Treatment target Risk stratification

Response to therapy Joint damage

Role of DMARDs Combination DMARDs Combination of Biologics and DMARDs

Management of patients failing TNFi Management of patients with discordant response Management of comorbidities

Obesity

Summary

Early diagnosis leads to better outcomes Appropriate assessment of PsA requires

assessment of all domains MDA is a valid target for treatment Treating to target may lead to better

response to therapy, less joint damage progression and less CVD