Rheumatoid Arthritis Role of Primary Care Professor Paul Emery ARC Professor of Rheumatology Head of...
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Rheumatoid ArthritisRole of Primary Care
Professor Paul EmeryARC Professor of RheumatologyHead of Academic Unit of Musculoskeletal Disease
University of Leeds Institute of Molecular Medicine
Clinical Director Rheumatology LTHT
Leeds, UK
What is Arthritis?
• Joint failure
• Two major types (causes)
Inflammatory: rheumatoid arthritis (RA)
and
Degenerative: osteoarthritis (OA)
Problems in Arthritis
• Perception: Nothing can be done
• Priority: Arthritis is non life-threatening cf Cancer/Heart disease
Not part of NSF
Problems in Arthritis
Presents late, but irrelevant
As even if could see early
• No accurate diagnosis
• No effective therapy
• All have changed
Arthritis:Arthritis: extent of the problem extent of the problem
• Arthritis and bone diseases are increasing in incidence, prevalence and importance
• Ageing population age wave• Arthritis alone most common symptom over 55• Predicted no.1 problem in future• Largest cause of medical sickness
Many patients referred inefficiently/inappropriately
Arthritis Arthritis – extent of the problem– extent of the problem
Arthritis Care Report [February, 2002]Arthritis Care Report [February, 2002]
• 1 in 5 of population has some form 1 in 5 of population has some form of arthritisof arthritis
• 72% of people with arthritis meet 72% of people with arthritis meet legal definition of disabilitylegal definition of disability
• 20% of GP consultations are 20% of GP consultations are arthritis related arthritis related (25% are dissatisfied (25% are dissatisfied with treatment)with treatment)
Impact on quality of lifeImpact on quality of life
Sprangers, Sprangers, 20002000
New Approaches
• Complete rethink required for diseases previously regarded as untreatable
• Successful therapies for many conditions• Assessment should be evidence-based and rapid• Rapid because either painful (delay leads to
chronicity) or serious (delay leads to fatality)missed “window of opportunity”
• Cost enormous - £billions, research money restricted
Strange Truths
• RA is curable
• It can only be done with primary care
• Leeds can be first to achieve it
RA Current Concepts
RHEUMATOID ARTHRITIS
Overview
• Chronic inflammatory disease of unknown etiology: multi-hit hypothesis
• Complex development: persistent inflammation in predisposed individual leads to chronicity
• Fluctuating clinical course characterized by-Progressive destruction of synovial joints with
loss of cartilage and bone-Damaged ligaments and tendons-Loss of physical function and quality of life-Premature death
• Estimated direct costs of RA were US $8.74 billion in 1994, 0.3% of the gross domestic product (GDP)
• In the UK, average RA outpatient cost/case/year was £798 (US $1,126) and £1,253 (US $1,769) per inpatient in 1997
• RA costs average:• 49% of cost of cancer• 68% of cost of stroke• 82% of cost of coronary heart disease • 5 times cost of motor vehicle accidents
• Indirect costs• 3 to 4 times higher than direct costs• Lifetime costs £500,000
RHEUMATOID ARTHRITIS
Economic Burden
• Impact on Patient:
• Moderate disability within 2 years of diagnosis, severe by 10 years (relentless spread; analogous to malignancy)
• Inability to work within 10 years of onset • approximately 50% of RA patients
• Feelings of helplessness and other psychological distress
• Potential inability to carry out social role
RHEUMATOID ARTHRITIS
Social and Psychological Burden
Adapted with permission from:Adapted with permission from:Choy EHS, Panayi GS.Choy EHS, Panayi GS. N Engl J Med N Engl J Med. 2001;344:907–916.. 2001;344:907–916.
RHEUMATOID ARTHRITIS
Disease Progression
EarlyEarlyRheumatoidRheumatoidArthritisArthritis
EstablishedEstablishedRheumatoidRheumatoidArthritisArthritis
NormalNormalKneeKneeJointJoint
– Symmetric joint pain– Swelling of small peripheral
joints– Morning joint stiffness of
variable duration
•Fatigue, malaise/depressionmay precede other symptoms•Insidious onset
•Life-long disease
RHEUMATOID ARTHRITIS
Presenting Signs and Symptoms
TREATMENT OF RHEUMATOID ARTHRITIS
Conventional General Approach
• Start treatment early to prevent joint damage
• Institute general therapeutic measures: education, exercise, rest, joint protection, physical therapy
• Prescribe medications for symptom relief
• Prescribe DMARDs (Disease Modifying anti-Rheumatic Drugs) to prevent joint damage and induce remission
TREATMENT OF RHEUMATOID ARTHRITIS
Goals of Therapy
• Relieve symptoms, including fatigue, pain, swelling, and stiffness
• Prevent joint destruction, loss of joint function, deformity, disability, and early death
• Preserve quality of life• Achieve clinical remission
Nodular, erosive rheumatoid arthritis
Early Arthritis Clinics (EAC)
WHY? - Damage occurs early - Results of failure to treat. - Model system of care. HOW? - Education, finance, enthusiasm. WHAT IF? - Reduced wait - Better outcome - Innovative approaches to therapy.
Early Treatment of RA and the Goal of Preventing Long-Term Disability
Severi
ty
InflammationFunction
Time
Ahmed K, Emery P.. Challenges in Rheumatoid Arthritis. Oxford, England: Blackwell Science; 1999:106-115.Ahmed K, Emery P.. Challenges in Rheumatoid Arthritis. Oxford, England: Blackwell Science; 1999:106-115.
Interventions
Paradigm
• Inflammation is bad
• Inflammation is treatable
Inflammation x Time = Damage
What is needed?
• Good contacts with primary care
• Education re importance of early phase
Inception cohorts (EAC) allow:
• Differentiating the effects of Drugs/Disability/Disease
• Prediction
• Better outcome for both good and poor outcome patients
Yorkshire Early Arthritis Register (YEAR): Background
• Leeds Early Arthritis Project (LEAP)
• Region wide (15 centres) register of all new RA patients
• Co-ordinated programme to standardise management and improve outcome of early RA on a regional basis
YEAR: Participating Centres
Delay in presentation of inflammatory arthritis
Mean time from first symptom to specialist appointment for patients with RA(Birmingham EAC)
• 1988 14.2 months• 1993 3.4 months
• Note: hard to see RA patients quicker
Which symptoms? Target Population?
• Early RA• Inflammatory arthritis• Potential inflammatory arthritis• All new onset non-traumatic arthritis
Target population depends on purpose of clinic and resources
• Logic for all inflammatory arthritis• Entry into secondary care
Practical Approach
Refer all patients with:• New onset arthritis (non-traumatic)
and/or• Symptoms of inflammation
– EM Stiffness– Swelling – Response to NSAIDs
– Are symptoms/signs accurate?
Seeing potential RA or all new arthritis?
Which Tests Before Referral?
• Acute phase response
• X ray
• RF/anti-CCP/ autoAb
• Or None
Reasons that Tests are Unhelpful
1. Waiting for results delays referral2. A large proportion of appropriate patients
will be negative1. X ray 80% 2. CRP 50%3. RF/CCP 40%
3. Negative tests deter referral4. Do anti-CCP if NOT referring
MRI at Presentation
• Presence of erosions
diagnostic prognostic -level of synovitis
-level of bony oedema
Size of US lesions seen by radiology (resolution) Wakefield et al A&R1999
• Xray sees 9% of small US lesions • Xray sees 57% of moderate/large US lesions i.e. Radiology insensitive for small lesions
Note• In early RA 90% of all HRUS lesions are small• In late RA 63% of all HRUS lesions are small
i.e. majority of erosions small (esp. early)
Radiology will miss most cortical breaks especially in early disease
Outcome of Early Assessment
• Over half of ACR (RA)patients seen and treated within 12 weeks went into remission
• After 12 weeks less than 10%
• Early treatment effective ?essential
No Yes
YesNo
No No Yes
Yes
Self LimitingSelf Limiting Undifferentiatedarthritis
Undifferentiatedarthritis
Confirmed RAConfirmed RA
ACR +veACR +veRecurrenceafter single CS dose
Recurrenceafter single CS dose
Symptomatic TreatmentSymptomatic Treatment Duration > 12 weeksDuration > 12 weeks
Inflammatory ArthritisInflammatory Arthritis
Early IA algorithm
Imaging
Sonography of Subclinical Synovitis
26 patients with clinical monoarthritis– 35% sonographic oligoarthritis (> 1
joint)
– 25% sonographic polyarthritis
Wakefield et al. Ann Rheum Dis 2004; 63:382-388
Clinical findings
Num
ber
of
join
ts
Prevalence of US detected synovitis in joints which were asymptomatic, clinically painful but not swollen, and clinically synovitis joints.
0100200300400500600700800
Asymptomatic Painful but notswollen
Clinical synovitis
Total number of jointsUS synovitis
Anti-TNFs: A major therapy
GoldPenicillamineSulfasalazine
Hydroxychloroquine
Steroid MTXNSAID
1930-40 1950 1960 1988 1995 1999+
Combo
Anti-TNF
Key therapeutics representing a dramatic improvement in treating RA patients
Clinical Remission by DAS28<2.6
*p<0.001 for adalimumab + MTX vs MTX alone and adalimumab alone
43
23 21
49
25 25
0
10
20
30
40
50
60
Adalimumab + MTX Adalimumab MTX
Week 52Week 104
% P
atie
nts
**
PREMIER Study
2.13
**
5.5**
**
Change in Total Sharp Score
PREMIER Study
000
10.4
5.7
3.5
* p<0.001 for adalimumab + MTX vs MTX alone and adalimumab alone** p<0.001 for adalimumab vs MTX alone
0
Ch
ang
e fr
om
Bas
elin
e
0
2
4
6
8
10
12
26 52 78 104
Adalimumab + MTX
Adalimumab
MTX
1.9
1.30.8
***
Very Early use of Anti-TNF
• Early RA
• Poor prognosis
• Previously untreated
• Double-blind, placebo-controlled/ Independent assessors
• All patients MTX +/- anti-TNF
TNF 20 Key study features
• Early RA• Poor prognosis (PISA>3)• Previously untreated• Frequent MRI assessments• Double-blind, placebo-controlled • Independent assessors• Benefits of anti-TNF/MTX over MTX alone
Quinn et al A&R 2005
MRI synovial volumes pre- & post- infliximab
N u m b er o f erosive sites
10
20
0 4 14 54T ime (weeks)
Num
ber
of e
rosi
ve s
ites
In flix im ab
P laceb o
anti-TNF at presentation produces long-lasting benefit (one year after stopping therapy)
Quinn et al A&R 2005
years-100
-80
-60
-40
-20
00 14 30 46 54 78 104
% c
ha
ng
e HAQ MTX + placebo
HAQ MTX + Infliximab
RAQoL MTX + placebo
RAQoL MTX + Infliximab
Anti-TNF treatmentAnti-TNF treatment 21
MTX TreatmentMTX Treatment
TNF Results at 2yrs
• Follow up 1 year after last infusion
• NO FLARES in responder patients
• New approach to therapy?
• Guide response/therapy especially in early disease
Coordinated Programme To Prevent
Arthritis
Dr Jackie NamRheumatology Fellow
Professor Paul EmeryArc Professor of Rheumatology
Academic Unit of Musculoskeletal DiseaseChapel Allerton Hospital
Hypotheses
In the pre-clinical phase of RA, patients present with non-specific musculoskeletal complaints
These patients can be identified by performing an anti-CCP antibody test
Doing a blood test in those patients who would not be otherwise referred, will enable us to see pre-RA patients earlier
Aims
1. To determine whether we can identify an enriched population of anti-CCP Ab (+) patients by screening those patients with new-onset, non-traumatic musculoskeletal complaints
2. To document the initial presenting complaint of these patients
3. To determine the initial cost of this community screening process
4. To develop a model for early diagnosis of RA
5. Prevent progression to RA
Endpoints
1. Proportion of community patients with new-onset, non-traumatic musculoskeletal complaints who are anti-CCP Ab (+)
2. Proportion of patients who develop an inflammatory arthritis (IA) by 12 months
3. Proportion of patients who develop RA by 12 months
How can you help in Primary Care?
Patients for referral:– Any new musculoskeletal complaint– ≥ 18 years
How can we help?Patient pack:
1. Patient information sheet with contact telephone nos. for the Rheumatology SpRs
2. Consent form3. Questionnaire4. Self addressed envelope5. Blood card for Anti-CCP testing
Blood testing
• Patients can then call the Rheumatology Registrar for further information and consent
• Blood will be taken at local phlebotomy centre
• Anti-CCP Ab tests performed weekly/fortnightly
• Results will be reviewed weekly by the Rheumatology Fellow
• Results will also be sent to the referring GP
Patients with positive anti-CCP Ab results
• Will be contacted and offered an OPD appointment at the CCP Clinic at CAH
• Followed-up 3 monthly for 12 months • Evaluated clinically, have blood tests and
imaging • Diagnosis at baseline and 12 months will be
evaluated
Patients with negative anti-CCP Ab results
• Will be contacted by telephone at 12 months and sent a questionnaire
• You may be contacted for their diagnosis
Conclusion
• Diagnosis of pre-RA patients
– Start effective therapy – Prevent disability – Improve quality of life