MAJOR CAUSES OF INFLAMMATORY POLYARTHRITIS

Infectious arthritisBacterial

Viral Other

Postinfectious (reactive) arthritisRheumatic fever Reactive arthritis Enteric infection

Other seronegative spondyloarthritidesAnkylosing spondylitis

Psoriatic arthritis Inflammatory bowel disease

Rheumatoid arthritis Inflammatory OA

Crystal-induced arthritisSystemic rheumatic illnesses: SLE, vasculitis, SSc, PM/DM

Other systemic illnesses: sarcoidosis, malignancy, subacute endocarditis

Quinn et al. How do you diagnose rheumatoid arthritis early. Best Pract Res Clin Rheumatol 2001;15a:49-66

Early diagnosis and intervention

In Rheumatoid arthritis and Psoriatic arthritis: Radiographic damage within weeks of onset Window of opportunity with early DMARD for

possible “cure” Both radiographic damage and disease activity are

independent predictors disability Polyarthritis may be 1st indicatior of systemic

illness (HIV, cancer, SLE)

2010 ACR/EULARClassification Criteria for RA

JOINT DISTRIBUTION (0-5)1 large joint 0

2-10 large joints 11-3 small joints (large joints not counted) 24-10 small joints (large joints not counted) 3>10 joints (at least one small joint) 5

SEROLOGY (0-3)Negative RF AND negative ACPA 0Low positive RF OR low positive ACPA 2

High positive RF OR high positive ACPA 3

SYMPTOM DURATION (0-1)<6 weeks 0≥6 weeks 1

ACUTE PHASE REACTANTS (0-1)Normal CRP AND normal ESR 0Abnormal CRP OR abnormal ESR 1

≥6 = definite RA

What if the score is <6?

Patient might fulfill the criteria…

Prospectively over time (cumulatively)

Retrospectively if data on all four domains have been adequately recorded in the past

What about patients that don’t meet criteria?

30-40% of patients presenting with synovitis will remain unclassified

As many as half will go into remission, and be off of medications in one year

About 1/3 will go onto to develop persistant synovitis, rheumatoid arthritis

Studies indicate that earlyDMARD use if started w/in critical window (<3months)may prevent progression to chronic arthritis

Options for Initial Therapy

Hydroxychloroquine Sulfasalazine Methotrexate Leflunomide Azathioprine Gold Minocycline TNF inhibitors Combination of above

Based on multiple studies ≈ 30% of patients will achieve DAS28 of ≤ 3.2 on MTX monotherapy (1-3)

1. BeSt. 2 year data. Ann Int Med 2007; 146:406-152. Swefot. Lancet 2009; 374:459-663. TEAR. Arthritis Rheum 2009; 60:S707

Combination Therapy: COBRA trial Patients with disease duration < 2years (mean duration 4

months) Compared SSZ monotherapy with combination therapy of:

Oral prednisone (60mg 7.5mg by 6 weeks d/cd by week 28MTX 15mg po (stopped at week 40)Sulfasalazine

Significant clinical improvement in combo group, but only while steroid on board

Less radiographic damage at week 56 with combination therapy

5 year follow up showed sustained suppression of the rate of radiographic progression, independent of subsequent treatment.

A Randomized Controlled Trial of Tight Control of Rheumatoid Arthritis (TICORA)

110 pts randomized, active RA < 5 years duration for 18 months.Two groups: usual therapy versus intensive therapy

*Intra-articular steroid injections used but biologics were not.

Grigor, Porter, Stirling, Capell. Lancet 2004:364:263-9

TICORA – Results (18 months)

Intensive group n = 55

Routine groupN = 55

Odds ration(95%) (p<0.001)

EULAR good response

80% 44% 3.6 (1.5-8.7)

EULAR remission 65% 16% 9.6 (3.8-24.3)

ACR 20 89% 64% 4.0 (1.5-10.5)

ACR 50 82% 45% 4.9 (2.1 – 11.4)

ACR 70 70% 18% 9.5 (3.9 – 23.0)

Grigor et al. Lancet 2004: 364:263-69

COMBINATION vs MONOTHERAPY in EARLY RA

Mono Double Triple I vs II I vs III II vs III

(P

Values)

ACR 50 49.1% 73.5% 87.9% <0.001 <0.001 <0.001

Remission 31.5% 44.6% 60.3% 0.007 0.007 0.007

No Xray progression

24.5% 64.2% 68.9% 0.001 0.001 0.210

Calguneri et al. Clin Exp Rheumatology 1999:17:699-704

*ERA trial: 63% no radiographic progression at 2 years

Goal: Tight control in the treatment of rheumatoid arthritis

Should we use combinations initially in all new patients or use a rapid step-up to combinations only in those that need it?

COBRA, FINRa-Co, Calguneri, PREMIER, all favor combinations initially.

TICORA shows that rapid step-up can be very effective, as does 2 year BeSt data and TEAR

TEAR shows no penalty for waiting (step up at 4-6 month mark)

Capturing patients with very early synovitis

Studies out of the UK have shown a dramatic reduction in delays to rheumatologic evaluation

Studies in the 1980’s, found the median delay from symptom onset to referral was over 20 months, in one large teaching hospital in Glasgow, UK

Subsequent studies in the 90’s indicated that most of the delay stemmed from time to seek initial medial care (avg 4months) and time to seeing rheumatologist another month

In Austria, nation-wide public campaign advising people with signs of inflammatory arthritis to contact their GP

Practice Points

Several studies suggest that the very early phase of disease may be pathologically distinct from established RA, which may represent a therapeutic window in which “cure” may be possible.

Rapid control of inflammation even in established RA with DMARD therapy has been shown to slow the progression of joint damage and disability.

Patients should be regularly followed to ensure “tight control” aiming for low disease activity or remission.