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STATE OF THE ARThritis
OsteoArthritis & Rheumatoid Arthritis
OSTEOARTHRITIS
Previously…
SOTA: OA Management Guidelines
◦ American College of Rheumatology 2012 recommendations for the use of nonpharmacologic
and pharmacologic therapies in osteoarthritis of the hand, hip, and knee
◦ OARSI guidelines for the non-surgical management of knee osteoarthritis (2014)
◦ Osteoarthritis Treatment & Management (Medscape 2016)
◦ 2016 Patellofemoral pain consensus statement from the 4th International Patellofemoral Pain
Research Retreat, Manchester. Part 1: Terminology, definitions, clinical examination, natural
history, patellofemoral osteoarthritis and patient-reported outcome measures
◦ 2016 Patellofemoral pain consensus statement from the 4th International Patellofemoral Pain
Research Retreat, Manchester. Part 2: recommended physical interventions (exercise, taping,
bracing, foot orthoses and combined interventions)
Conditionally Recommend:
ACR 2012:
Nonpharmacologic
recommendations for the
management of knee OA
Participate in self-management programs
Receive manual therapy in combination with supervised exercise
Receive psychosocial interventions
Use medially directed patellar taping
Strongly Recommend:
Wear medially wedged insoles if they have lateral compartment OA
Wear laterally wedged subtalar strapped insoles if they have medial compartment OA
Participate in cardiovascular (aerobic) and/or resistance
land-based exercise
Participate in aquatic exercise
Be instructed in the use of thermal agents
Receive walking aids, as needed
Participate in tai chi programs
Lose weight (for persons who are overweight)
Be treated with traditional Chinese acupuncture*
Be instructed in the use of transcutaneous electrical stimulation*
*These modalities are conditionally recommended only when the patient with knee osteoarthritis (OA) has chronic moderate to severe pain and is a candidate for total knee arthroplasty but either is
unwilling to undergo the procedure, has comorbid medical conditions, or is taking concomitant medications that lead to a relative or absolute contraindication to surgery or a decision by the surgeon
not to recommend the procedure.
ACR 2012:
Pharmacologic recommendations for the initial management of knee OA
Conditionally Recommend:
Conditionally Do Not Recommend:
No Recommendations:
Chondroitin Sulfate
Intra-articular Hyaluronates
Glucosamine
Duloxetine
Topical Capsaicin
Opioid Analgesics
Acetaminophen
Oral NSAIDs
Topical NSAIDs
Tramadol
Intra-articular Corticosteroid
Injections
Going Beyond SOTA…
Treatment Targets
&
Targeted Treatments
Going Beyond SOTA…
Target Acquisition
through
Pattern Recognition
OA Phenotypes
Phenotypes
Prevalence
Pathophysiology
Presentation
Chronic Pain
16-19%
Central sensitization
Peripheral spreading, fibromyalgia
Inflammatory
16-30%
IL1/IL6/TNF, crystals
Synovitis, effusion
Leptin, insulin resistance, hsCRP
Obesity, hypertension, DM,
dyslipidaemia, gout, fatty liver, OSA
Metabolic
Syndrome
Metabolic
Bone/Cartilage
0.2-1.3%
P1NP, COMP, NTX, CTX
Hypertrophic/atropic bone
Mechanical
Overload
12-22%
Biomechanical imbalance,
malalignment
Severe unicompartmental
degeneration, past injuries
Minimal Joint
Disease
17-47%
Mixed/undifferentiated pathogenesis Mild symptoms, slow progression
Identification of clinical phenotypes in knee osteoarthritis: a systematic review of the literature
A. Dell’Isola, R. Allan, S. L. Smith, S. S. P. Marreiros, M. Steultjens
BMC Musculoskeletal Disorders 2016 17:425
Going Beyond SOTA…
Treat
to
Target
T2T for OA
◦ Imaging to confirm diagnosis and quantify cartilage damage
◦ Imaging to pinpoint pain generator:
◦ MSUS for soft tissue pathologies (bursitis, tendinosis, enthesopathy, synovitis,
crystal deposition)
◦ MRI for bone marrow oedema (BME)
◦ DECT for subclinical urate & calcium (BCP/CPP) deposits
◦ Targeted treatment of pathologies:
◦ BME: anti-resorptives
◦ Crystals: Colchicine, ULT
◦ Synovitis: IA corticosteroid, MTX, PRP/ACP
◦ Biomechanic assessment: strength training, taping, podiatry
◦ Full-thickness chondral defect: Viscosupplement, ACI repair, MSC regeneration
State Of My Art…
◦ Identify source(s) of pain: history, examination, imaging
◦ Identify precipitating/aggravating factor(s) and central sensitisation
◦ Refer for biomechanical assessment and therapy
◦ SYSADOA/DMOAD 3-months’ trial:
◦ Glucosamine/Chondroitin Sulphate
◦ Avocado Soybean Unsaponifiables
◦ Strontium Ranelate
◦ Orthobiologics: Viscosupplementation, PRP/ACP, MSC
◦ Recurrent effusions:
◦ Exclude chronic infection (TB), tumour (PVNS), crystal deposition (MSU, BCP, CPP)
◦ Consider IA corticosteroid, Colchicine, Spironolactone, Methotrexate, lavage, synovectomy
◦ Repair, Replace, Regenerate
RHEUMATOID
ARTHRITIS
2010
ACR/EULAR
“Diagnostic
Criteria”
for RA
2010
EULAR
Recommendations
for the
Targeted
Treatment
of RA:
A
3-Phase
Approach
2014 EULAR Recommendations for Treating RA to Target
2015 ACR Guideline for the Treatment of Early RA
2015 ACR Guideline for the Treatment of Established RA
ACR-EULAR 2011 Definition of Remission
 For clinical practice
• Boolean – SJC, TJC, PtGA all ≤1
• Index-based – CDAI ≤2.8
CDAI=SJC+TJC+PhGA+PtGA
 For clinical trials
• Boolean – SJC, TJC, PtGA, CRP all ≤1
• Index-based – SDAI ≤3.3
SDAI=SJC+TJC+PhGA+PtGA+ CRP (mg/dl)
Going beyond SOTA… State Of My Art
Predicting Development of RA
◦ Power Doppler ultrasound (PDUS)
synovitis
• Ultrasound for early diagnosis of synovitis
and tenosynovitis
◦ ACPA positive
• Therapeutic trial (1 week):
• Low-to-moderate dose corticosteroid
• Fast-acting, short-duration targeted therapy
• Etanercept
• Tocilizumab
• Abatacept
• Tofacitinib
Going beyond SOTA… State Of My Art
Predicting Rapid Radiographic
Progression
◦ RF &/or ACPA positive
◦ 14-3-3η >0.5 ng/ml
◦ High ESR/CRP at initial presentation
◦ Erosions already present at diagnosis
◦ Inadequate response to initial appropriately
aggressive treatment:
◦ moderate-dose corticosteroids
◦ targeted agents
• Combination bridging therapy:
• Fast-acting DMARD (corticosteroid,
targeted agents) for 3-6 months to induce
remission
• Slow-acting DMARD (MTX, Leflunomide,
Rituximab) for at least 1 year to maintain
remission
• Intra-articular corticosteroid
• Subcutaneous MTX 25-30mg/wk before
combination csDMARDs
Going beyond SOTA… State Of My Art
Predicting Response to Therapies
◦ TNF-α promoter 308 GG genotype predicts
for response to anti-TNF
◦ DNA methylation at LRPAP1 gene predicts
for response to Etanercept
◦ Synovial myeloid phenotype predicts for
response to anti-TNF, lymphocytic
phenotype to anti-IL6
◦ Low Osteopontin at baseline predicts for
response to Tocilizumab
◦ High NK cells at baseline predicts for
response to Tocilizumab
◦ Positive RF & ACPA predicts for response
to Abatacept & Rituximab
• First-line targeted therapy: anti-TNF
• Anti-TNF failure:
• Primary failure ~ switch mode of action:
•
•
•
•
Anti-IL6 (Tocilizumab, Sarilumab, Sirukumab)
T-cell costimulation blockade (Abatacept)
B-cell depletion (Rituximab)
JAK inhibitor (Tofacitinib, Baricitinib)
• Secondary failure ~ switch class:
• Soluble receptor fusion protein (Etanercept,
Certolizumab)
• Monoclonal antibodies (Infliximab,
Adalimumab, Golimumab)
• First-line multi-targeting therapy: pan-JAK
inhibitor
Going beyond SOTA… State Of My Art
Predicting Tapering Feasibility
◦ Negative serologies (RF, ACPA) & shared
epitope
• Only consider tapering in sustained
EULAR remission
◦ Undifferentiated disease
• Taper off targeted therapy before
csDMARD
◦ Male, non-smoker
◦ Low DAS & HAQ at baseline
◦ Short duration of active disease (early
remission)
◦ No or minimal radiographic joint damage
o Deep (PDUS grade 0-1) & prolonged
remission
• Monitor symptoms with PDUS for early
flare
• Managing flares (and disappointment):
• Search for triggers (eg infections, dysbiosis)
• Abridged re-induction
• Protracted maintenance for longer sustained
remission
Fast & Furious
Treat To Target
Whatever It Takes
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