Transcript Early Arthritis Clinics - Back to Medical School

Rheumatoid Arthritis
Role of Primary Care
Professor Paul Emery
ARC Professor of Rheumatology
Head 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 lifethreatening 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:
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 – extent of the problem
Arthritis Care Report [February, 2002]
• 1 in 5 of population has some form of
arthritis
• 72% of people with arthritis meet legal
definition of disability
• 20% of GP consultations are arthritis
related (25% are dissatisfied with treatment)
Impact on quality of life
Sprangers, 2000
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
RHEUMATOID ARTHRITIS
Economic Burden
• 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
Social and Psychological
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
Disease Progression
Normal
Knee
Joint
Early
Rheumatoid
Arthritis
Established
Rheumatoid
Arthritis
Adapted with permission from:
Choy EHS, Panayi GS. N Engl J Med. 2001;344:907–916.
RHEUMATOID ARTHRITIS
Presenting Signs and Symptoms
– Symmetric joint pain
– Swelling of small peripheral
joints
– Morning joint stiffness of
variable duration
•Fatigue, malaise/depression
may precede other symptoms
•Insidious onset
•Life-long disease
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
Severity
Inflammation
Function
Time
Interventions
Ahmed K, Emery P.. Challenges in Rheumatoid Arthritis. Oxford, England: Blackwell Science;
1999:106-115.
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
Seeing potential RA or all new arthritis?
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?
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 referral
2. A large proportion of appropriate patients
will be negative
1.
2.
3.
X ray 80%
CRP 50%
RF/CCP 40%
3. Negative tests deter referral
4. 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
Early IA algorithm
Inflammatory Arthritis
No
Imaging
Symptomatic Treatment
Yes
Duration > 12 weeks
No
Recurrence
after single CS dose
No
Self Limiting
Yes
Yes
ACR +ve
No
Undifferentiated
arthritis
Yes
Confirmed RA
Sonography of Subclinical
Synovitis
Total number of joints
US synovitis
Number of joints
26 patients with clinical monoarthritis
800
700
600
500
400
300
200
100
0
– 35% sonographic oligoarthritis (> 1
joint)
– 25% sonographic
polyarthritis
Asymptomatic
Painful but not
swollen
Clinical synovitis
Clinical findings
Prevalence of US detected synovitis in joints which were asymptomatic,
clinically painful but not swollen, and clinically synovitis joints.
Wakefield et al. Ann Rheum Dis 2004; 63:382-388
Anti-TNFs: A major therapy
Key therapeutics representing a dramatic
improvement in treating RA patients
1930-40
Gold
Penicillamine
Sulfasalazine
Hydroxychloroquine
1950
1960
Steroid
NSAID
1988 1995 1999+
MTX Combo
Anti-TNF
PREMIER Study
Clinical Remission
by DAS28<2.6
60
% Patients
50
Week 52
Week 104
*
*
49
43
40
30
23
25
25
21
20
10
0
Adalimumab + MTX
Adalimumab
*p<0.001 for adalimumab + MTX vs MTX alone and adalimumab alone
MTX
PREMIER Study
Change in Total Sharp Score
Adalimumab + MTX
12
Adalimumab
10
10.4
MTX
8
6
**5.5
5.7
4
3.5
**
2
2.1
0
0
0
*0.8
26
**
3
* 1.9
*1.3
52
* p<0.001 for adalimumab + MTX vs MTX alone and adalimumab alone
** p<0.001 for adalimumab vs MTX alone
78
104
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- & postinfliximab
Number of erosive sites
Number of erosive sites
Infliximab
Placebo
20
10
0
4
14
Time (weeks)
54
anti-TNF at presentation produces long-lasting
benefit (one year after stopping therapy)
Quinn et al A&R 2005
MTX Treatment
0
0
14
30
46
54
78
104
% change
-20
HAQ MTX + placebo
-40
HAQ MTX + Infliximab
RAQoL MTX + placebo
RAQoL MTX + Infliximab
-60
-80
-100
Anti-TNF treatment
1
years
2
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 Nam
Rheumatology Fellow
Professor Paul Emery
Arc Professor of Rheumatology
Academic Unit of Musculoskeletal Disease
Chapel 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 newonset, 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 form
3. Questionnaire
4. Self addressed envelope
5. 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