RHEUMATOID ARTHRITIS MANAGEMENT
- An autoimmune multisystem disease.
- NSAIDs – Provide symptomatic relief (no effect on disease progression).
Classification of rheumatoid arthritis management:
- 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.
- 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.
- 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.).
|Infliximab||3–10 mg/kg||Intravenous||0,2,6,10,14 weeks, then every 8 weeks|
|Adalimumab||40 mg||Subcutaneous||Once in 2 weeks|
|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.
- 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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