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