PHAR3912 - Rheumatoid Arthritis

what is rheumatoid arthritis?

chronic autoimmune disease of uncontrolled synovial tissue proliferation, excess fluid production, destruction, and joint deformity

what are the modifiable and non-modifiable risk factors of rheumatoid arthritis?

non-modifiable: female, genetics, family Hx

modifiable: smoking, obesity, infection, diet, pregnancy (disease remission)

what are the Sx and Dx for rheumatoid arthritis?

Sx: symmetrical joint and swelling ("swan neck"), morning stiffness, reduced range of motion, joint deformity

Dx: seropositive RF and ACPA antibodies (high disease severity)

rheumatoid arthritis vs osteoarthritis?

OA: unilateral joint space lowering + non-symmetrical

RA: bilateral joint space lowering + symmetrical

what are the immunological mechanisms of rheumatoid arthritis?

stimulus -> citrullination -> antigen-presenting cell recognise as foreign -> migrate to lymph -> activates T cells -> trigger immune response -> B cell produce antibodies -> plasma cells -> chronic inflammation -> ACPAs + RF -> worsen inflammation

what are the key drug targets of rheumatoid arthritis Tx?

to prevent immune response triggering chronic inflammation

methotrexate acts on T and B cells to reduce proliferation

outline the Tx approach for rheumatoid arthritis

goal: remission or low disease activity

1. NSAID (continued due to slow onset of DMARD)

2. DMARD (fist line)

3. biologics (if DMARD ineffective)

4. steroids (reduce inflammation)

5. analgesics for pain

what is the non-pharmacological management strategies for rheumatoid arthritis?

exercise

diet (Mediterranean)

smoking cessation

patient education

what is the MOA, cautions, side effects, and example of csDMARDs?

first-line for RA

MOA: inhibit folate metabolism in proliferation B and T cells -> less cytokines -> less inflammation

cautions: bone marrow diseases

side effects: GI -> take folic acid

example: methotrexate (same time every week)

what other csDMARDs are used in triple therapy?

leflunomide (if methotrexate contraindicated)

sulfasalazine (inhibit COX)

hydroxychloroquine (inhibit APC -> no T-cell activation)

what is the safety and monitoring requirements of csDMARDs?

monitor common toxicities (renal, hepatic)

GI upset

sulphur allergy

pregnancy

combination therapy = increase efficacy, decrease toxicity because lower doses

what is the MOA of bDMARDs and tsDMARDs and their efficacy/safety?

in combination with a csDMARD

MOA: inhibit cytokine signalling -> reduce inflammatory response -> reduces immune response (SE)

safety: infection screening, liver/renal checks

what occurs during rheumatoid arthritis Sx exacerbation (flare) ?

activation of circulating b-cell -> peripheral blood of pre-inflammatory mesenchymal cells (PRIME) -> migrate to tissue -> flare

what are the common triggers of a rheumatoid arthritis flare?

weather

hormonal changes

exhaustion

stress

medication changes

diet (alcohol + smoking)

infection

what is the Tx approach to rheumatoid arthritis flare management?

1. non-pharmacological (heat therapy)

2. short-term NSAID

3. short term low-dose corticosteroid

4. temporary DMARD dose increase

5. evaluate biological therapy escalation

what are the referral red flags for a rheumatoid arthritis flare?

fever, weight loss, malaise, nerve pain, rash

what are the comorbidities of rheumatoid arthritis?

1. CVD: JAK inhibitors, corticosteroids, NSAIDS can increase risk, DMARD decrease risk

2. osteoporosis: long-term glucocorticoid use, reduced activity

3. depression: chronic pain, stress, systemic inflammation

What special population consideration should be made for rheumatoid arthritis management?

consider long-term fertility

surgery: csDMARD, bDMARD continued, tsDMARD, systemic corticoids, should be paused

vaccinations: withheld at start of therapy