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