Early Arthritis Clinic

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Early Arthritis Clinic

• Jack Cush, MD

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What do I have to do to get this patient seen?

• 53 yoWM under evaluation for eosinophilia
• No Meds PMHx prostatitis ROS negative
• Only c/o R knee effusion/warmth x 12 weeks
• Negative CBC, BM Bx, Stool O/P, ANA, DNA, ESR,
  UA, CXR (pending RF, CRP)
• Hematology W/U exhausted
• How to w/u the swollen R knee (maybe L too)?
• Next availalable rheumatology appt?
• Who you gonna call?

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Early Arthritis Diagnostic Algorithm
Chronicity Joint swelling gt 12 wks ?
No
Yes
Synovial Swelling gt3 Joints (Symmetric, Typical)
Possible RA
No
Yes
Yes
No
Serum RF/CCP Positive?
Assess Severity
Slowly Progressive RA
High titer RF CCP Xray Erosions Many Swollen
Jts Nodules/Extra-artic HLA-DRB1/SE HAQ gt 1.4
No
RA
Yes
Aggressive RA High Risk Patient
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US City Populatoins and Expected NEW RA Cases
every Year (28-56,000)
City Population Rheums Pts/Rheum New RA/yr
Ft. Smith, AR 81,518 2 8366 16
Ft Collins, CO 124,665 2 62,322 24
Little Rock, AR 184,055 22 8366 37
Huntsville, AL 162,536 5 32,507 32
Birmingham, AL 239,416 45(30) 5320 47
Toledo, OH 309,106 7 44,158 62
Omaha, NE 399,106 12 33,279 80
Denver, CO 560,415 40(29) 14,010 112
Charlotte, NC 580,597 14 36,328 116
Nashville, TN 648,882 25 29,955 138
Louisville, KY 698,080 18 38,782 140
SanAntonio, TX 1,194,222 30(24) 39,807 238
Dallas, TX 1,211,467 46 (29) 26,336 242
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10.3 Million w/ Chronic Joint Symptoms Have Never
Seen an MD

• 2001 CDC, BRFSS adult telephone survey (gt18yrs)
• 2001 estimated 47.5 million with CJS
• 10.3 million have not seen MD (2.0 million w/
  activity limitations). Risk Factors
• lt HS education, excellent-good health, no
  insurance, no PCP, no activity limitation and
  engaged in regular physical activity

876,000
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Early RA Window of Opportunity
RA/Inflammatory Arthritis Continuom

• MD? PCP Rheums
• s? 800,000 725,000
• Sxs? Wks-Mos Mos-Yrs

Few Joints Many
Normal XRay Erosive
Possible Remission Rare?
Full Time Employed? Disability
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Early RA A problematic diagnosis

• Most patients will not meet ACR criteria
• Most patients will not be RF ( 19- 45)
• Most patients will not seek medical care
• Most PCPs prefer to evaluate, rather than refer
• Many patients will remit with symptomatic Rx
• Histopathology similar RA, ERA, UPA
• Few features to distinguish RA vs UPA
• Duration, Jts, RF, CCP, ESR/CRP
• Cost of diagnositic evaluation is higher in UPA

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Early RA Take Home Points

• Early RA defined as lt 12 weeks the earlier the
  better
• Articular erosions/damage evident early
• ? Delay in Rx is Disastrous!
• 1st DMARD Choice is CRITICAL!
• Use Best DMARD First!
• Multiple Trials show signif. downstream effects
• High Risk Early RA patients Can Be defined
• RF and CCP are Predictive and OMINOUS together
• DMARDs work, COMBOs and Biologics are Better!
• Referral Rules gt3 jts, squeeze test, Sx 6-12
  wks, RF
• Challenge how to facillitate early referral

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Short Delay of Therapy Affected Radiographic
Outcome
Sharp Score
14
12
10
Delayed Treatment median 123 days
8
6
Early Treatment median 15 days
4
2
0
0
6
12
18
24
Time (months)
Lard LR, et al. Am J Med. 2001111446-451.
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Early Referral, Early DMARD in VERANell VP,
Machold KP, Eberl G, et al. Rheumatology 2004

• Case-controlled, parallel study
• Very early RA (VERA) dz duration 3 mos
• Late early RA (LERA) lt12 mos to DMARD
• DMARDS SSZ, MTX, CQ, CYA, LEF, Combo
• Evaluated at 36 mos DAS28, Larsen score
• At study end DAS28 improved 2.81.5 in the VERA
  vs. 1.71.2 in the LERA group (Plt0.05)
• Larsen scores showed a statistically significant
  retardation of progression in VERA vs. LERA

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Percent of Patients Fulfilling ACR Response
Criteria After 36 Months of Follow-Up
LERAVERA1


Patients With Fulfilled Criteria
Plt0.05
Nell V. et al., Rheumatology 2004 43906-14.
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Radiographic Changes in LERA and VERA1 Patients,
Indicated by the Larsen Score
LERAVERA1




Larsen Score
Months after DMARD initiation
Plt0.05
Nell V. et al., Rheumatology 2004 43906-14.
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4 Treatment Strategies in Early RA
Sequential Monotherapyn125 Step-Up Therapy n128 Initial Combination Therapy n133 Initial MTX Biologic Therapy n128
MTX 45 SSZ21 LEF19 MTX biologic15 MTX41 MTX SSZ30 MTX SSZ HCQ16 MTX SSZ HCQ PRED13 MTX SSZ PRED81 MTX CSA PRED11 MTX biologic8 MTX biologic86 SSZ8 LEF6
De Vries-Bouwstra JK, et al. Arthritis Rheum.
2003483649.
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Percentage of Patients in Remission DAS44 lt 1.6
Discontinuation of Biologic
De Vries-Bouwstra JK, et al. Arthritis Rheum.
2003483649.
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Aggressive Therapy Example COBRA 1997
Study design Double-blind, randomized study
Population 155 early active RA patients (no more than 2 years from ACR diagnosis)
Treatment groups Prednisolone (60?7.5 mg/day step-down), MTX (7.5 mg/week), SSZ (2 g/day) vs SSZ (2 g/day) Prednisolone and MTX tapered and stopped after 28 weeks and 40 weeks, respectively
Follow-up 56 weeks
ACR American College of Rheumatology COBRA
Combinatietherapie Bij Reumatoide Artritis MTX
methotrexate SSZ sulfasalazine.
Boers M, et al. Lancet. 1997350309-318.
Landewe R, et al. Arthritis Rheum.
200246347-356.
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Step-Down Therapy
COBRA Trial
Clinical Outcome
Combined Treatment
Sulphasalazine
Pooled Index Score
Prednisolone
Methotrexate
Sulfasalazine
Time (Weeks)
Adapted from Boers M, et al. Lancet.
1997350309-318.
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Early Aggressive Therapy Provides for Long-term
Results
Damage Progression (Sharp/van der Heijde)
40
SSZ 8.6 points/y
30
COBRA 5.4 points/y
20
10
0
0
1
2
3
4
5
Years
Landewe RB, et al. Arthritis Rheum.
200246347-356.
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Short Delay of Therapy Predicted Remission at 2
Years
Fin-RA Co Study
Study design 2-year, open-label, parallel-group, randomized trial
Population N195 disease duration lt 2 years prednisone and DMARD naive
Treatment groups Monotherapy Sulfasalazine (2-3 g) prednisolone (5-10 mg) initially, switching to methotrexate (7.5 to 15 mg/week) if inadequate response Combination therapy Methotrexate 7.5-15 mg Hydroxychloroquine 300 mg Sulphasalazine 1-2 g Prednisolone 5-10 mg
ACR preliminary criteria for remission were used.
Mottonen T, et al. Lancet. 19993531568-1573.
Arthritis Rheum 46894, 2002
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Fin-Co-RA Work Disability Early RA5 Yr Followup
of Single vs Triple DMARD
GREATER Sick Leave Work Disability Retirement
ß119
ß79
ßannual regression coefficient
Puolakka, K. et al., Arthritis Rheum
20045055-62.
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Etanercept in Early RA ACR Response Rates at
Year 2
100
MTX 20 mg Etanercept 25 mg
P 0.005
72
80
P NS
59
60
49
of Patients
42
P NS
40
29
24
20
0
ACR-20
ACR-50
ACR-70
Genovese MC, et al. Arthritis Rheum.
20024614431450.
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Radiographic Change at Year 2
Etanercept ERA Trial
Total Sharp Score (p0.001)
Erosions (p0.001)
Joint Space Narrowing (p0.0163)
4
3.2
Mean Change From Baseline
1.9
2
1.3
0.7
1.0
0.5
0
Etanercept 25 mg
Methotrexate
Adapted from Genovese MC, et al. Arthritis
Rheum. 2002461443-1450.
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ASPIRE MTX INFLIXIMAB IN EARLY RA

• 54 wk phase IV DBRPCT
• MTX vs MTX Infliximab (3 or 6 mg/kg)
• Early RA lt 3 yrs duration ( mean 7 mos)
• N1050 125 centers worldwide 455 random
• Inclusion
• 12 Tender 10 Swollen (30 Tend 19 Swoll)
• RF or CRP or XRAY erosion ( gt 80)

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Presbyterian Hospital of DallasEarly Arthritis
Clinic

• Tuesday Afternoons
• Jack Cush, MD
• Andres Quiceno, MD
• Kathyrn Dao, MD

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• EARLY ARTHRITIS CLINIC REFERRAL
• (Patients must have arthrititis for lt 12
  months)
• Patient Name
  Age ___________________
• Referring Physician
  Phone Fax
• Previously Seen a Rheumatologist? NO YES Whom
  __________
  
• Symptoms Began
  Diagnosis Date _________
• Reason for Referral (Choose any that apply) ?
• Acute Pain
• Acute Swelling
• Chronic Pain
• Chronic Swelling
• Widespread Pain
• Affected Joints Hand Feet Shoulder
  Knee Hip Back Neck
• ANA (Result Pattern
  )
• RF (Result )
• High ESR or CRP (Result
  )
• Osteoarthritis
• Lupus
• Rheumatoid arthritis

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Results Diagnoses 53 pts

• 10 wrongfully referred gt 12 mos
• 5 SLE (5 malar, 2dsDNA, 1 Sm, 3 pred)
• 1 ANA() arthralgia
• 5 RA/inflammatory polyarthritis (1 resolved)
• 3 SpA 1 PsA
• 3 PSS and CREST (2 pred, 1 CTX)
• 3 Myositis and Myopathy NOS
• 3 Osteoarthritis
• 5 Fibromyalgia/myofascial pain syndrome
• 4 No known dx (dx pending)
• 1 each Urticaria, sialadenitis, drug-induced
  lupus, bursitis

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Diagnosing Early Arthritis in the CommunityPHD
Early Arthritis Campaign (PEAK)

• Why Bother?
• Who will benefit?
• Are PCPs and Specialists interested?
• What do PCPs want?
• How will it work?
• Goal to identify gt 90 of new onset RA patients
  in the next year?
• Cooperating Clinics Internal medicine, Family
  practice, Emergency Departments, Orthopedics, IM
  subspecialties, OBGYN

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Multidisciplinary Awareness Campaign

• Goal increase awareness, facillitate early
  referral diagnosis of serious rheumatic diseases
• Cachement PHD Community 1 million
• Outcome diagnosis of Early RA (N 40? 240)
• Role Players Rheums, PR, Marketing, Phone,
  Administration, Managed Care, Study Coordinators
• Tools Mailings, Signage, Publications, Local Ad
  Campaign, DTC mailings
• Success depends on PCP community

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PHD Rheumatologists are Alligned

• Convinced that early diagnosis and early
  aggressive Rx will positively impact outcomes
• Can be accomplished without effecting patient
  load/flow. (work smarter, not harder)
• Agree to study this Cooperative Effort
• Protocol for intake, testing, DMARDs, Data.
• Create access to Consultation for PCPs, Patients
• Secondarily educate facillitate referrals

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Rheumatologists Buy In(w/in practice, hospital,
network, system, Univ, state)

• Need to be convinced that early diagnosis and
  early aggressive Rx will positively impact
  outcomes
• Be convinced that such a program need not affect
  income (work smarter, not harder)
• Importance of Cooperative Efforts
• Protocol for Standardization of intake, care,
  testing, etc.
• Goal is to create productive access to your
  specialty services for PCPs and Patients
• Secondarily educate facillitate referrals

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PCP Misconceptions

• Referrals are easy (how many? How prompt?)
• Diagnosis can be made by lab tests, xrays
• Response to therapy confirms diagnosis
• Everyone responds to Steroids or NSAIDs
• Those that dont cant be helped

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Out with the Old in with the New
Diagnosis LESS SPECIFIC Newer MORE SPECIFIC
Inflammation ESR C-Reactive Protein
RA Rheumatoid Factor Anti-CCP Antibodies
Lupus ANA dsDNA, Sm
Gout Uric Acid MSU Crystals
Vasculitis pANCA C-ANCA
Arthritis XRays Clinical Findings
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Physician Education

• 3 Main Messages
• Rapid easy access to the Rheum of choice
• Prompt appointments with rapid diagnosis and
  treatment
• Rapid notice of outcome and return of patient

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Whats the Motivation for PCPs

• LOVE (Patient Satisfaction)
• MONEY (Arthritis Patients are not time efficient)
• Time Money
• Rheumatology voodoo medicine (ANA1000)
• Access to Rheumatologists

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Physician Education Programs

• PCPs dont want Rheum Education
• They Want Access to Rheumatologists
• Dear Dr. Letter informs of program, reminds
• RheumaKNOWLEDGY Cards (Pocket info)
• Referral Rules Card
• Broadcast Fax/Frequent Newsletters
• Group lunches/breakfasts with Rheums
• Invite PCPs, Orthos, NP/PA
• CME Forums
• BEST Immediate Feedback on patients referred

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EAC Models

• EAC Clinic (_at_PHD Tuesday is Early Arthritis day)
• Physician Extender (NP/PA) intake/screening
• Prescreen Chart review, FAX requests, MD to MD
  referral
• Flexible Scheduling (promote, hold, fill spots)
• Meet and Greet Rapid Slots
• Free Arthritis Screening Clinics
• Model Depends on the objective/setting
• Private solo, group, multispecialty group
• University, Academic, Clinical Trials
• Government/Municipal

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Must There be A Patient Focused Effort?

• Most patients dont seek medical care
• Most newly afflicted patients dont know who to
  see PCP, Ortho, GYN, Chiropracter?
• Whats a Rheumatologist?
• Purveyor of Rumors
• Specializes in Interior Design
• How will PCP sector perceive a public advertising
  campaign encouraging new onset joint complaints
  to see PCP?
• To self refer to Early arthritis screening
  clinics?
• Currently EAC plans to only accept referred pts

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Motivating Message for Pts with arthritis gt 12 wks

1. You are at risk of having a chronic disease for
   the rest of your adult life
2. This disease will alter your lifestyle, ability
   to function, play, and age gracefully
3. You may also be at higher risk for developing
   heart disease, osteoporosis, stomach ulcers,
   lymphoma and premature death
4. Early and Aggressive expert treatment can avert
   these outcomes

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If you build it.they will come

• Goal increase awareness, facillitate early
  referral diagnosis of serious rheumatic diseases
• Target Rheums, PCPs, Orthos, OBGYNs, NP, PA,
  Chiropractors, Patients, Media, Managed Care
• Cachement Your Community N ?
• Outcome diagnosis earlier Rx
• Role Players Rheums, PR, Marketing, Phone,
  Administration, Managed Care, Study Coordinators
• Tools Mailings, Signage, Publications, Ad
  Campaign, DTC mailings
• PCP Dear Dr., Rheum Education, Newletters

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Guidelines for Referral to the Early Arthritis
ClinicEmery P, et al. Ann Rheum Dis 2002
61290-297

• Differential Diagnosis
• Inflammatory
• RA
• UPA/USP
• Viral arthritis
• SpA
• Crystal arthritis
• Autoimmune
• SLE/UCTD
• Behcets
• Vasculitis
• Cryoglobulinemia
• Noninflammatory
• Osteoarthritis
• Hemochromatosis
• Others
• Infectious arthritis
• PMR
• SBE

• Refer when there is clinical suspicion!
• gt 3 swollen Joints
• MTP/MCP squeeze test
• AM stiffness gt 30 minutes
• Rheumatoid factor
• Elevated ESR or C-Reactive Protein
• (NSAIDs/Prednisone may obscure findings)