RHEUMATOID ARTHRITIS MANAGEMENT

Rheumatoid arthritis (RA):

• An autoimmune multisystem disease.

General management:

• NSAIDs – Provide symptomatic relief (no effect on disease progression).

Classification of rheumatoid arthritis management:

1. Corticosteroids:

• Low-dose corticosteroids – Used as bridge & adjunctive therapy.
• Bridge therapy means until DMARDs start.
• Adjunctive therapy (with DMARDs).

II). Disease-modifying anti-rheumatoid drugs (DMARDs):

• Slows disease progression but act slowly (takes 6 weeks to 6 months).

1. Synthetic DMARDs:

Methotrexate

• 1^st choice DMARD.
• Used at much lower doses (7.5 mg weekly).

Sulfasalazine:

• Metabolized to sulfapyridine & 5-aminosalicylic acid.
• Sulfapyridine – Active moiety in RA.
• 5-aminosalicylic acid – Useful for ulcerative colitis.
• Used in methotrexate contraindicated patients.

Leflunomide:

• Prodrug.
• MOA: Inhibits dihydro orotate dehydrogenase enzyme.
• Enzyme is required for pyrimidine synthesis.
• Hence B cell growth is arrested.
• Fast-acting – Acts within 4 weeks.
• Cholestyramine decreases toxicity – by enhancing clearance.

Chloroquine & hydroxychloroquine:

• Antimalarial drugs useful as DMARDs.
• Hydoxychloroquine preferred over chloroquine – Due to reduced retinal damage.

Minocycline:

• Only for early mild cases.
• Works better during 1^st first year of RA.
• MOA: Anti-inflammatory property & ability to inhibit collagenase.

Tofacitinib:

• Janus kinase 3 inhibitor.
• Approved for severe RA refractory to methotrexate.
• Effective orally.
• Patient screening for latent TB to be done prior treatment.

III) Biological DMARDS

TNF-α blocking agents:

• TNF- α: Major role in joint destruction.
• MOA: Blocks TNF-α action.
• Cause activation of latent tuberculosis.
• Drugs: Etanercept (s.c.), adalimumab (s.c.), infliximab (i.v.), golimumab (s.c.) & certolizumab (s.c.).

Drug	Dose	Route	Frequency
Infliximab	3–10 mg/kg	Intravenous	0,2,6,10,14 weeks, then every 8 weeks
Etanercept	50 mg	Subcutaneous	Weekly
Adalimumab	40 mg	Subcutaneous	Once in 2 weeks
Golimumab	50 mg	Subcutaneous	Monthly
Certolizumab	200-400 mg	Subcutaneous	Every 2-4 weeks.

IV) Monoclonal antibody:

Tocilizumab

• Monoclonal antibody against IL-6.
• Combined with methotrexate.

Rituximab

• Monoclonal antibody depleting B-cells.
• Also combined with methotrexate.

V) Co-stimulation inhibitors:

• Abatacept & belatacept.
• MOA: Acts by inhibiting CD80 & CD86 co-stimulatory molecules on antigen presenting cells.
• Interaction of CD80 & CD86 with CD 28 on T-cells is necessary for T-cell activation.
• Indicated for RA resistant to methotrexate & TNF-? inhibitors combination.

VI) Older drugs

Gold & d-penicillamine:

• Highly efficacious DMARDs.
• Rarely used – Due to severe toxic reactions.
• Gold salts used orally (auranofin) & intramuscularly (aurothiomalate).
• Adverse effect – (Most common) Dermatitis –> kidney & liver damage, peripheral neuropathy, pulmonary fibrosis, encephalopathy & bone marrow depression.

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