1. IMPROVING EARLY DIAGNOSIS AND TREATMENT OF RHEUMATOID ARTHRITIS Michael Lockwood, MD, FACP, FACR Rheumatology Indiana University Health Arnett

2. Presentation of Case March 1994: 48 yo w F smoker, joint pain and swelling, RF 74 June 1994 started hydroxychloroquin September 1994 feeling much better May 1998 started methotrexate April 2002 found benefit with COX 2 Selective NSAIDs August 2002 deformity and nodulosis 2005 methotrexate was increased May 2006: DAS 4.02, Hand films January 2007: Infliximab started Could a different outcome have been achieved?

3. 11/25/19968/19/2006

4. Rheumatoid Arthritis Cure Why is it important? Severe disability after 20 year: 19% Lifetime Costs: $225,000 - $370, 000 Excess Deaths: Mortality Ratio = 2.26 Excess Cardiovascular events = 4x Increases risk of coronary artery disease = Type 2 diabetes Wolfe, A&R 37(4), p. 481

5. Rheumatoid Arthritis Approach to Therapy Timing Korpela, A&R vol. 50, pp 2072-81  Before 4 months:  Combination 42%  Single Drug 35%  After 4 months  Combination 42%  Single Drug 11% Mottonen, A&R, vol. 46, pp.894-98

6. Rheumatoid Arthritis Advantage of Early Assessment Timing Van der Linden, A&R Vol. 62 pp 3537-3547

7. Rheumatoid Arthritis History Onset: Weeks to Months – Can be Palindromic onset – Can have pauciarticular onset Constitutional features – Morning stiffness lasting for hours Functional Questions

8. Rheumatoid Arthritis Epidemiology Women:Men 3:1 Peak onset age 30-55 Incidence 30/100,000 Prevalence – 1% Caucasians – 0.1% rural Africans

9. Rheumatoid Arthritis Physical

11. Rheumatoid Arthritis Deformities Ulnar Deviation Swan neck deformities Boutenaire deformities

12. Rheumatoid Arthritis Deformities Bayonet Deformities MTP Subluxation

13. Rheumatoid Arthritis Deformities Atlantoaxial Instability MRI

14. Rheumatoid Arthritis Extraarticular Involvement Rheumatoid Nodules

15. Rheumatoid Arthritis Extraarticular Involvement Rheumatoid Vasculitis

16. Rheumatoid Arthritis Extraarticular Involvement Pulmonary Pleurasy

17. Rheumatoid Factor  Antibodies to Fc portion of IgG  75-80% of Patients have during course of disease  Useful for prognosis

18. Cyclic Citrullinated Peptide Antibodies (anti CCP) Schellekens, A&R, Vol 43, pp. 155-163

19. Rheumatoid Arthritis X-Ray

21. Rheumatoid Arthritis Classification 1987 Criteria Arnett, A&R, Vol 31, pp. 315-324

22. Rheumatoid Arthritis Classification 2010 Criteria Aletaha, A&R, Vol 62, pp. 2569-2581

23. Rheumatoid Arthritis Pathology

24. Choy, E. H.S. et al. N Engl J Med 2001;344:907-916 Pathogenesis of Rheumatoid Arthritis

25. Rheumatoid Arthritis Pannus

26. Rheumatoid Arthritis Approach to Therapy Triple Drug Therapy O’Dell, NEJM vol. 334, pp 1287-1291  Triple Drug: 77% get 50 % improvement  Methotrexate: 33%  Plaquenil/Sulfasalazine: 40%

27. Choy, E. H.S. et al. N Engl J Med 2001;344:907-916 Cytokine Signaling Pathways Involved in Inflammatory Arthritis

28. Rheumatoid Arthritis How do we proceed? Aggressive approach, <5 yr disease, monthy followup DAS calculated monthly Aggressively escalating therapy Goal: DAS remission or low disease activity Results: ACR 50 = 84% vs 40% standard tx. – Decrease erosions – Total Costs less Grigor, Lancet, Vol. 364, pp. 263-269

29. Rheumatoid Arthritis Implementation DAS scoring & aggressive approach in a community rheumatology practice

30. Problem 1 A 32 year old man presents with fatigue, low back pain and morning stiffness lasting 15 minutes. He notes that the back pain seems to get worse as he works through his day. He is a machinist at a local factory. What should you do next? A.Start a Medrol (methylprednisolone) dose pack B.Check a rheumatoid factor (RF), cyclic citrullinated peptide antibody (CCP), and an antinuclear antibody (ANA) C.Refer to physical therapy for back strengthening and instruction in back protection D.Get a lumbar sacral xray 3 views E.Get a MRI of the back.

31. Problem 2 A 26 year old women presents with a 4 week history of swelling and tenderness of all of the MCPs, PIPs and the MTPs of the feet. This is confirmed on physical examination. There are no other stigmata on examination. Her labs are remarkable for a sed rate of 35 but a negative rheumatoid factor (RF), CCP, and ANA. Her hand a feet xrays are normal. Her most likely diagnosis is: A.Systemic lupus erythematosus B.Rheumatoid arthritis C.Psoriatic arthritis D.Fibromyalgia

32. Problem 3 What treatment would you initiate for the above patient? A.Monotherapy with methotrexate, hydroxychloroquin, or sulfasalazine but follow serial DAS (disease activity score) and treat to target. B.Combination therapy with methotrexate, hydroxychloroquin, and sulfasalazine but follow serial DAS (disease activity score) and treat to target. C.Combination therapy with methotrexate and a TNF blocker but follow serial DAS and treat to target.

33. Problem 4 A 45 year old women presents with swelling and pain in the joints of 8 months duration, morning stiffness lasting several hours, and she finds it difficult to do her work. She has swelling and tenderness in most of the MCPs, PIPs, and MTPs. There is also swelling of the wrist, ankles, elbows, and one knee. Her sed rate is 60, and she has a high titre positive rheumatoid factor and cyclic citrullinated peptic (CCP). The ANA is 1:160. Her hand films do show joint space narrowing in one of the MCP and there is an erosion of a couple of the PIP. What treatment would you initiate for the patient? A.Monotherapy with methotrexate, hydroxychloroquin, or sulfasalazine but follow serial DAS (disease activity score) and treat to target B.Combination therapy with methotrexate, hydroxychloroquin, and sulfasalazine but follow serial DAS (disease activity score) and treat to target. C.Combination therapy with methotrexate and a TNF blocker but follow serial DAS and treat to target