1. Rheumatoid Arthiritis
Burhan Khan

2. Background
is a chronic autoimmune disease characterized by inflammation of the synovium
polyarthritis affects particularly in the hands and feet, and is frequently symmetrical.
inflammation results in the release of cytokines (ie, interleukins [IL-1 and IL-6] and tumor necrosis factor [TNF])  activates macrophage-like synoviocytes  further release of cytokines  chronic inflammatory state
IL-6 affects the neuroendocrine system and neuropsychological behavior.
Goal of targeted medications for the RA is to interfere with the inflammatory signaling by targeting the
Cytokine
its receptor
or the downstream signaling pathway (eg, Janus kinases [JAK])

4. Clinical Presentation
History
joint pain & swelling & morning stiffness lasts >30 minutes, stiffness after prolonged sitting
symptoms that have persisted for longer than 6 weeks
Physical examination
distribution of swollen or tender joints and limited joint motion
extra-articular disease manifestations (ie, rheumatoid nodules)
Symmetrical joint involvement
metacarpophalangeal (MCP) & proximal interphalangeal (PIP) joints of the fingers, the interphalangeal joints of the thumbs, the wrists, the elbows, the shoulders, the ankles, the knees, and the metatarsophalangeal (MTP) joints of the toes.
Early signs of RA can often be found in the hands where joint tenderness and reduced grip strength are key indicators

6. Diagnosis
ESR; CRP; CBC with differential, liver and kidney function tests, serum uric acid
Urinalysis
rheumatoid factor (RF) & anti-cyclic citrullinated peptide antibody (ACPA); ANA; anti-double stranded DNA
Infectious disease screening
eg tuberculosis, HBV, HCV
N.B.
both RF and ACPA may be negative in 20% to 50% of patients with RA OR
they may precede the clinical manifestation of RA by many years

7. Radiographic imaging
Imaging of hands, wrists, and feet is essential to establish a baseline for monitoring disease progression, exclude other diagnoses, and detect characteristic joint erosion.
MRI and ultrasound are not as commonly used to detect joint erosion in RA patients, but due to their increased sensitivity (compared to radiography); they may be useful in patients with negative radiographs or obesity.

8. ACR & EUALR diagnostic criteria
European League Against Rheumatism (EULAR)

9. Nomenclature of RA Pharmacology
disease-modifying antirheumatic drugs (DMARDs)
conventional synthetic (cDMARDs or csDMARDs)
MTX, Leflunomide, Hydroxychloroquine, sulfasalazine, azathioprine, cyclosporine, D-penicillamine, minocycline
targeted synthetic (tDMARDs or tsDMARDs),
biological originator (bDMARDs or boDMARDs)
biosimilar DMARDs (bsDMARDs)

10. Treat-to-target (T2T) approach
DMARD monotherapy (preferably MTX) regardless of disease activity
combination DMARDs
DMARDs + Biologics:
DMARD + tumor necrosis factor
inhibitor (TNFi) or
non-TNF biologic or
tofacitinib

12. Escalating T2T
After TNFi  another TNFi or a non-TNF biologic with or without MTX
Disease activity after TNFi therapy should be treated with a non-TNF biologic or tofacitinib with or without MTX
Disease activity on a non-TNF biologic should receive a second non-TNF biologic or tofacitinib with or without MTX

13. Non-pharmacological measures
physical
occupational
psychological approaches
Pharmacological treatment options:
synthetic DMARDs (hydroxychloroquine, leflunomide, sulfasalazine, and methotrexate)
NSAIDS
Glucocorticoids
TNF1: Adalimumab, Eternercept, Golimumab, Infliximab, Certolizumab
Anti-IL1: Anakinra
Anti IL6: Toclizumab
Co-stimulatory modulator: Abatacept
Jak inhibitor: Tofacitinib
B-cell depletion: Rituximab, Belimumab

16. Disease Assessment patient-reported outcome measures (PROMs)
RAPID3
Pt-DAS28 (physician component removed from DAS28)
evaluation by a physician
CDAI (clinical disease activity index)
SDAI (simplified disease activity index)
DAS28 (disease activity score 28-joint count)

18. CDAI (clinical disease activity index)
outcome measure that is the arithmetic sum of 28 joints
the swollen joint count (SJC)
tender joint count (TJC)
patient's global assessment (PGA)
evaluator's global assessment (EGA)
Score: 0 to 76
No labs needed

19. SDAI (simplified disease activity index)
the arithmetic sum of
SJC
TJC
PGA
EGA &
C-reactive protein (CRP)
Score: 0 to 100

20. DAS28 (disease activity score 28-joint count)
a weighed assessment that includes
SJC
TJC
PGA &
CRP or ESR