Rheumatoid Arthiritis Burhan Khan

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])

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

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

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.

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

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)

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

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

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

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)

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

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

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