IMPROVING EARLY DIAGNOSIS AND TREATMENT OF RHEUMATOID

ARTHRITISMichael Lockwood, MD, FACP, FACR

RheumatologyIndiana University Health

Arnett

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?

11/25/1996 8/19/2006

Rheumatoid Arthritis CureWhy 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

Rheumatoid ArthritisApproach 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

Rheumatoid ArthritisAdvantage of Early Assessment

Timing

Van der Linden, A&R Vol. 62 pp 3537-3547

Rheumatoid Arthritis History

• Onset: Weeks to Months– Can be Palindromic onset– Can have pauciarticular onset

• Constitutional features– Morning stiffness lasting for hours

• Functional Questions

Rheumatoid Arthritis Epidemiology

• Women:Men 3:1• Peak onset age 30-55• Incidence 30/100,000• Prevalence

– 1% Caucasians– 0.1% rural Africans

Rheumatoid Arthritis Physical

Rheumatoid Arthritis Physical

Rheumatoid Arthritis Deformities

Ulnar Deviation

Swan neck deformities

Boutenaire deformities

Rheumatoid Arthritis Deformities

Bayonet Deformities

MTP Subluxation

Rheumatoid Arthritis Deformities

Atlantoaxial Instability

MRI

Rheumatoid Arthritis Extraarticular Involvement

Rheumatoid Nodules

Rheumatoid Arthritis Extraarticular Involvement

Rheumatoid Vasculitis

Rheumatoid Arthritis Extraarticular Involvement

Pulmonary

•Pleurasy

Rheumatoid Factor

Antibodies to Fc portion of IgG

75-80% of Patients have during course of disease

Useful for prognosis

Cyclic Citrullinated PeptideAntibodies (anti CCP)

Schellekens, A&R, Vol 43, pp. 155-163

Rheumatoid Arthritis X-Ray

Rheumatoid Arthritis X-Ray

Rheumatoid ArthritisClassification 1987 Criteria

Arnett, A&R, Vol 31, pp. 315-324

Rheumatoid ArthritisClassification 2010 Criteria

Aletaha, A&R, Vol 62, pp. 2569-2581

Rheumatoid ArthritisPathology

Choy, E. H.S. et al. N Engl J Med 2001;344:907-916

Pathogenesis of Rheumatoid Arthritis

Rheumatoid ArthritisPannus

Rheumatoid ArthritisApproach to Therapy

Triple Drug Therapy

O’Dell, NEJM vol. 334, pp 1287-1291

Triple Drug: 77% get 50 % improvement

Methotrexate: 33%

Plaquenil/Sulfasalazine: 40%

Choy, E. H.S. et al. N Engl J Med 2001;344:907-916

Cytokine Signaling Pathways Involved in Inflammatory Arthritis

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

Rheumatoid Arthritis

Implementation DAS scoring &

aggressive approach in a

community rheumatology

practice

Arnett #

Pain Count

Swelling Count

VAS Patient

WSR

DAS

Comment

Date

I________________________________________________________________INot Active

at allExtremely

Active

Physician Assessment

PainSwelling

Patient Assessment of Disease Activity

DAS28 < 2.6 Remission

DAS28 2.6 to < 3.2 Low Disease Activity

DAS28 3.2 to 5.1 Moderate disease Activity

DAS28 >5.1 High Disease Activity

Last Name First Name Birth Date

Problem 1A 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 packB. 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 viewsE. Get a MRI of the back.

Problem 2A 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 erythematosusB. Rheumatoid arthritisC. Psoriatic arthritisD. Fibromyalgia

Problem 3What 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.

Problem 4A 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