1. Early Arthritis Clinic Jack Cush, MD

2. What do I have to do to get this patient seen? 53 yoWM under evaluation for eosinophilia53 yoWM under evaluation for eosinophilia No Meds; PMHx prostatitis; ROS negativeNo Meds; PMHx prostatitis; ROS negative Only c/o R knee effusion/warmth x 12 weeksOnly c/o R knee effusion/warmth x 12 weeks Negative: CBC, BM Bx, Stool O/P, ANA, DNA, ESR, UA, CXR (pending RF, CRP)Negative: CBC, BM Bx, Stool O/P, ANA, DNA, ESR, UA, CXR (pending RF, CRP) Hematology W/U exhaustedHematology W/U exhausted –How to w/u the swollen R knee (maybe L too)? Next availalable rheumatology appt?Next availalable rheumatology appt? Who you gonna call?Who you gonna call?

3. Early Arthritis Diagnostic Algorithm Chronicity: Joint swelling > 12 wks ? Serum RF/CCP Positive? Yes Possible RA RA Crystal arthritis Reactive arthritis Chlamydial arthritis Viral arthritis Palindromic Rheum. Early arthritis:observe Synovial Swelling >3 Joints (Symmetric, Typical) Undifferentiated Polyarthritis Psoriatic arthritis Reactive arthritis Spondyloarthropathy Pseudogout Connective Tissue Dz Polymyalgia Rheumatica Inflammatory OA Hemochromatosis Diff Dx < 3 jts No High titer RF CCP+ Xray Erosions Many Swollen Jts Nodules/Extra-artic HLA-DRB1/SE HAQ > 1.4 Assess Severity Aggressive RA “High Risk Patient” SlowlyProgressive RA RA No Yes Yes Yes

4. CityPopulationRheumsPts/Rheum New RA/yr Ft. Smith, AR 81,5182836616 Ft Collins, CO 124,665262,32224 Little Rock, AR 184,05522836637 Huntsville, AL 162,536532,50732 Birmingham, AL 239,41645(30)532047 Toledo, OH 309,106744,15862 Omaha, NE 399,1061233,27980 Denver, CO 560,41540(29)14,010112 Charlotte, NC 580,5971436,328116 Nashville, TN 648,8822529,955138 Louisville, KY 698,0801838,782140 SanAntonio, TX 1,194,22230(24)39,807238 Dallas, TX 1,211,467 46 (29) 26,336242 US City Populatoins and Expected NEW RA Cases every Year (28-56,000)

5. 10.3 Million w/ Chronic Joint Symptoms Have Never Seen an MD 2001 CDC, BRFSS adult telephone survey (>18yrs)2001 CDC, BRFSS adult telephone survey (>18yrs) 2001 estimated 47.5 million with CJS2001 estimated 47.5 million with CJS 10.3 million have not seen MD (~2.0 million w/ activity limitations). Risk Factors:10.3 million have not seen MD (~2.0 million w/ activity limitations). Risk Factors: –< HS education, excellent- good health, no insurance, no PCP, no activity limitation and engaged in regular physical activity 876,000

6. Early RA: Window of Opportunity MD?PCPRheums #’s?800,000725,000 Sxs?Wks-MosMos-Yrs RA/Inflammatory Arthritis Continuom FewJointsMany NormalXRayErosive PossibleRemissionRare? Full Time Employed?Disability

7. Early RA: A problematic diagnosis Most patients will not meet ACR criteriaMost patients will not meet ACR criteria Most patients will not be RF+ ( 19- 45%)Most patients will not be RF+ ( 19- 45%) Most patients will not seek medical careMost patients will not seek medical care Most PCPs prefer to evaluate, rather than referMost PCPs prefer to evaluate, rather than refer Many patients will remit with symptomatic RxMany patients will remit with symptomatic Rx Histopathology similar: RA, ERA, UPAHistopathology similar: RA, ERA, UPA Few features to distinguish RA vs UPAFew features to distinguish RA vs UPA Duration, #Jts, RF+, CCP+, ESR/CRP Duration, #Jts, RF+, CCP+, ESR/CRP Cost of diagnositic evaluation is higher in UPACost of diagnositic evaluation is higher in UPA

8. Early RA defined as < 12 weeks; the earlier the betterEarly RA defined as < 12 weeks; the earlier the better Articular erosions/damage evident earlyArticular erosions/damage evident early  Delay in Rx is Disastrous!  Delay in Rx is Disastrous! 1 st DMARD Choice is CRITICAL!1 st DMARD Choice is CRITICAL! –Use Best DMARD First! –Multiple Trials show signif. downstream effects High Risk Early RA patients Can Be definedHigh Risk Early RA patients Can Be defined RF and CCP are Predictive and OMINOUS togetherRF and CCP are Predictive and OMINOUS together DMARDs work, COMBOs and Biologics are Better!DMARDs work, COMBOs and Biologics are Better! Referral Rules: >3 jts, squeeze test, Sx 6-12 wks, RF+Referral Rules: >3 jts, squeeze test, Sx 6-12 wks, RF+ Challenge: how to facillitate early referralChallenge: how to facillitate early referral Early RA: Take Home Points

9. Short Delay of Therapy Affected Radiographic Outcome Lard LR, et al. Am J Med. 2001;111:446-451. Time (months) 0 2 4 6 8 10 12 14 06121824 Early Treatment = median 15 days Delayed Treatment = median 123 days Sharp Score

10. Case-controlled, parallel studyCase-controlled, parallel study Very early RA (VERA): dz duration 3 mosVery early RA (VERA): dz duration 3 mos Late early RA (LERA): <12 mos to DMARDLate early RA (LERA): <12 mos to DMARD DMARDS: SSZ, MTX, CQ, CYA, LEF, ComboDMARDS: SSZ, MTX, CQ, CYA, LEF, Combo Evaluated at 36 mos: DAS28, Larsen scoreEvaluated at 36 mos: DAS28, Larsen score –At study end DAS28 improved 2.8±1.5 in the VERA vs. 1.7±1.2 in the LERA group (P<0.05) –Larsen scores showed a statistically significant retardation of progression in VERA vs. LERA Early Referral, Early DMARD in VERA Nell VP, Machold KP, Eberl G, et al. Rheumatology 2004

11. Percent of Patients Fulfilling ACR Response Criteria After 36 Months of Follow-Up % Patients With Fulfilled Criteria * P<0.05 Nell V. et al., Rheumatology 2004; 43:906-14. * * LERA VERA1

12. Radiographic Changes in LERA and VERA1 Patients, Indicated by the Larsen Score Larsen Score Months after DMARD initiation * P<0.05 Nell V. et al., Rheumatology 2004; 43:906-14. * * LERA VERA1 * *

13. Sequential Monotherapy n=125 Step-Up Therapy n=128 Initial Combination Therapy n=133 Initial MTX + Biologic Therapy n=128 MTX 45% SSZ 21% LEF 19% MTX + biologic 15% MTX 41% MTX + SSZ 30% MTX + SSZ + HCQ 16% MTX + SSZ + HCQ + PRED 13% MTX + SSZ + PRED 81% MTX + CSA + PRED 11% MTX + biologic 8% MTX + biologic 86% SSZ 8% LEF 6% De Vries-Bouwstra JK, et al. Arthritis Rheum. 2003;48:3649. 4 Treatment Strategies in Early RA

14. Percentage of Patients in Remission: DAS44 < 1.6 Discontinuation of Biologic De Vries-Bouwstra JK, et al. Arthritis Rheum. 2003;48:3649.

15. 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 (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, respectivelyPrednisolone and MTX tapered and stopped after 28 weeks and 40 weeks, respectively Follow-up 56 weeks Boers M, et al. Lancet. 1997;350:309-318. Landewe R, et al. Arthritis Rheum. 2002:46:347-356. ACR = American College of Rheumatology; COBRA = Combinatietherapie Bij Reumatoide Artritis; MTX = methotrexate; SSZ = sulfasalazine.

16. Step-Down Therapy COBRA Trial Adapted from: Boers M, et al. Lancet. 1997;350:309-318. Clinical Outcome Time (Weeks) Pooled Index Score Prednisolone Methotrexate Sulfasalazine Combined Treatment Sulphasalazine

17. Early Aggressive Therapy Provides for Long-term Results P=0.008 0 10 20 30 40 012345 Damage Progression (Sharp/van der Heijde) Years COBRA: 5.4 points/y SSZ: 8.6 points/y Landewe RB, et al. Arthritis Rheum. 2002;46:347-356.

18. Short Delay of Therapy Predicted Remission* at 2 Years Study design 2-year, open-label, parallel-group, randomized trial Population N=195; disease duration < 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 Methotrexate7.5-15 mg Hydroxychloroquine300 mg Sulphasalazine1-2 g Prednisolone5-10 mg Fin-RA Co Study Mottonen T, et al. Lancet. 1999;353:1568-1573. Arthritis Rheum 46:894, 2002 *ACR preliminary criteria for remission were used.

19. Fin-Co-RA Work Disability Early RA 5 Yr Followup of Single vs Triple DMARD Puolakka, K. et al., Arthritis Rheum 2004;50:55-62. ß=119 ß=79 ß=annual regression coefficient GREATER Sick Leave Work Disability Retirement

20. Genovese MC, et al. Arthritis Rheum. 2002;46:1443–1450. % of Patients 0 20 40 60 80 59 72 42 49 24 29 100 ACR-20ACR-50 ACR-70 MTX 20 mg Etanercept 25 mg P = 0.005 P = NS Etanercept in Early RA: ACR Response Rates at Year 2

21. 1.9 1.0 Mean Change From Baseline 3.2 1.3 1.3 0 2 4 Etanercept 25 mg Total Sharp Score (p=0.001) 0.7 0.5 Methotrexate Joint Space Narrowing (p=0.0163) Erosions (p=0.001) Radiographic Change at Year 2 Adapted from: Genovese MC, et al. Arthritis Rheum. 2002;46:1443-1450. Etanercept ERA Trial

22. ASPIRE: MTX & INFLIXIMAB IN EARLY RA 54 wk phase IV DBRPCT – – MTX vs MTX + Infliximab (3 or 6 mg/kg) Early RA < 3 yrs duration ( mean ~ 7 mos) N=1050; 125 centers worldwide; 4:5:5 random Inclusion – –12 Tender & 10 Swollen (30 Tend & 19 Swoll) – –RF+ or CRP^ or XRAY erosion ( > 80%)

24. Presbyterian Hospital of Dallas Early Arthritis Clinic Tuesday Afternoons Jack Cush, MD Andres Quiceno, MD Kathyrn Dao, MD

25. EARLY ARTHRITIS CLINIC REFERRAL (Patients must have “arthrititis” for < 12 months) Patient Name : Age :___________________ Referring Physician Phone # Fax # Previously Seen a Rheumatologist? NOYESWhom: __________ 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   Gout   Fibromyalgia   Low back pain   Sjogrens syndrome   Scleroderma   Polymyositis/dermatomyositis   Vasculitis Please attach copies of recent labs, xrays, H&P or discharge summary

26. Results: Diagnoses 53 pts 10 wrongfully referred > 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

27. Diagnosing Early Arthritis in the Community PHD Early Arthritis Campaign (PEAK) Why Bother?Why Bother? Who will benefit?Who will benefit? Are PCPs and Specialists interested?Are PCPs and Specialists interested? What do PCPs want?What do PCPs want? How will it work?How will it work? Goal: to identify > 90% of new onset RA patients in the next year?Goal: to identify > 90% of new onset RA patients in the next year? Cooperating Clinics: Internal medicine, Family practice, Emergency Departments, Orthopedics, IM subspecialties, OBGYNCooperating Clinics: Internal medicine, Family practice, Emergency Departments, Orthopedics, IM subspecialties, OBGYN

28. Multidisciplinary Awareness Campaign Goal: increase awareness, facillitate early referral diagnosis of serious rheumatic diseasesGoal: increase awareness, facillitate early referral diagnosis of serious rheumatic diseases Cachement: PHD Community 1 millionCachement: PHD Community 1 million Outcome: diagnosis of Early RA (N= 40  240)Outcome: diagnosis of Early RA (N= 40  240) Role Players: Rheums, PR, Marketing, Phone, Administration, Managed Care, Study CoordinatorsRole Players: Rheums, PR, Marketing, Phone, Administration, Managed Care, Study Coordinators Tools: Mailings, Signage, Publications, Local Ad Campaign, DTC mailingsTools: Mailings, Signage, Publications, Local Ad Campaign, DTC mailings Success depends on PCP communitySuccess depends on PCP community

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

30. 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 outcomesNeed 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)Be convinced that such a program need not affect income (work smarter, not harder) Importance of Cooperative EffortsImportance of Cooperative Efforts –Protocol for Standardization of intake, care, testing, etc. Goal is to create productive access to your specialty services for PCPs and PatientsGoal is to create productive access to your specialty services for PCPs and Patients –Secondarily educate: facillitate referrals

31. PCP Misconceptions Referrals are easy (how many? How prompt?)Referrals are easy (how many? How prompt?) Diagnosis can be made by lab tests, xraysDiagnosis can be made by lab tests, xrays Response to therapy confirms diagnosisResponse to therapy confirms diagnosis Everyone responds to Steroids or NSAIDsEveryone responds to Steroids or NSAIDs –Those that don’t cant be helped

32. Out with the Old in with the New Diagnosis LESS SPECIFIC Newer MORE SPECIFIC InflammationESR C-Reactive Protein RA Rheumatoid Factor Anti-CCP Antibodies LupusANA dsDNA, Sm Gout Uric Acid MSU Crystals VasculitispANCAC-ANCA ArthritisXRays Clinical Findings

33. Physician Education 3 Main Messages3 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

34. LOVE (Patient Satisfaction)LOVE (Patient Satisfaction) MONEY (Arthritis Patients are not time efficient)MONEY (Arthritis Patients are not time efficient) –Time = Money –Rheumatology = voodoo medicine (ANA1000) Access to RheumatologistsAccess to Rheumatologists Whats the Motivation for PCPs

35. Physician Education Programs PCPs don’t want Rheum EducationPCPs don’t want Rheum Education –They Want Access to Rheumatologists Dear Dr. Letter: informs of program, remindsDear Dr. Letter: informs of program, reminds RheumaKNOWLEDGY Cards (Pocket info)RheumaKNOWLEDGY Cards (Pocket info) Referral Rules CardReferral Rules Card Broadcast Fax/Frequent NewslettersBroadcast Fax/Frequent Newsletters Group lunches/breakfasts with RheumsGroup lunches/breakfasts with Rheums –Invite PCPs, Orthos, NP/PA CME ForumsCME Forums BEST: Immediate Feedback on patients referredBEST: Immediate Feedback on patients referred

36. EAC Models EAC Clinic (@PHD Tuesday is Early Arthritis day)EAC Clinic (@PHD Tuesday is Early Arthritis day) Physician Extender (NP/PA) intake/screeningPhysician Extender (NP/PA) intake/screening Prescreen: Chart review, FAX requests, MD to MD referralPrescreen: Chart review, FAX requests, MD to MD referral Flexible Scheduling (promote, hold, fill spots)Flexible Scheduling (promote, hold, fill spots) Meet and Greet Rapid SlotsMeet and Greet Rapid Slots Free Arthritis Screening ClinicsFree Arthritis Screening Clinics Model Depends on the objective/settingModel Depends on the objective/setting –Private solo, group, multispecialty group –University, Academic, Clinical Trials –Government/Municipal

37. Must There be A Patient Focused Effort? Most patients don’t seek medical careMost patients don’t seek medical care Most newly afflicted patients don’t know who to see – PCP, Ortho, GYN, Chiropracter?Most newly afflicted patients don’t know who to see – PCP, Ortho, GYN, Chiropracter? Whats a Rheumatologist?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?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 ptsCurrently: EAC plans to only accept referred pts

38. Motivating Message for Pts with arthritis > 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

39. Goal: increase awareness, facillitate early referral diagnosis of serious rheumatic diseasesGoal: increase awareness, facillitate early referral diagnosis of serious rheumatic diseases Target: Rheums, PCPs, Orthos, OBGYNs, NP, PA, Chiropractors, Patients, Media, Managed CareTarget: Rheums, PCPs, Orthos, OBGYNs, NP, PA, Chiropractors, Patients, Media, Managed Care Cachement: Your Community N = ?Cachement: Your Community N = ? Outcome: diagnosis & earlier RxOutcome: diagnosis & earlier Rx Role Players: Rheums, PR, Marketing, Phone, Administration, Managed Care, Study CoordinatorsRole Players: Rheums, PR, Marketing, Phone, Administration, Managed Care, Study Coordinators Tools: Mailings, Signage, Publications, Ad Campaign, DTC mailingsTools: Mailings, Signage, Publications, Ad Campaign, DTC mailings PCP: Dear Dr., Rheum Education, NewlettersPCP: Dear Dr., Rheum Education, Newletters “If you build it….they will come”

40. Guidelines for Referral to the Early Arthritis Clinic Emery P, et al. Ann Rheum Dis 2002 61:290-297 Refer when there is clinical suspicion! > 3 swollen Joints> 3 swollen Joints + MTP/MCP “squeeze test”+ MTP/MCP “squeeze test” AM stiffness > 30 minutesAM stiffness > 30 minutes + Rheumatoid factor+ Rheumatoid factor Elevated ESR or C-Reactive ProteinElevated ESR or C-Reactive Protein (NSAIDs/Prednisone may obscure findings) Differential DiagnosisInflammatory RARA UPA/USPUPA/USP Viral arthritisViral arthritis SpASpA Crystal arthritisCrystal arthritisAutoimmune SLE/UCTDSLE/UCTD BehcetsBehcets VasculitisVasculitis CryoglobulinemiaCryoglobulinemiaNoninflammatory OsteoarthritisOsteoarthritis HemochromatosisHemochromatosisOthers Infectious arthritisInfectious arthritis PMRPMR SBESBE Serum sicknessSerum sickness