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:


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


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


  • 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.
Other drug groups:

Chloroquine & hydroxychloroquine:

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


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


  • 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:


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


  • 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.

Exam Important

  • Disease-modifying anti-rheumatoid drugs (DMARDs) slow disease progression but act slowly (takes 6 weeks to 6 months).
  • Methotrexate is the 1st choice DMARD for RA.
  • Leflunomide is a prodrug which acts by inhibiting dihydroorotate dehydrogenase enzyme.
  • Chloroquine & hydroxychloroquine are antimalarial drugs useful as DMARDs.
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