Disease Modifying

Antirheumatic Drugs
By: Himanshu Tyagi
2nd Professional MBBS
SGT Medical College, Hospital & Research Institute
 Rheumatoid Arthritis
• Rheumatoid arthritis (RA) is an autoimmune disease in which there is
joint inflammation, synovial proliferation and destruction of articular
cartilage.
• RA is a chronic progressive, crippling disorder with a waxing and
waning course.
• Multiple small joints of hands and feet are preferentially affected;
deformities are produced as the disease progresses.
•
 Treatment of RA

NSAIDs or Steroids DMARDs or SAARDs

Decrease pain and Slows down the disease
inflammation. progression

No effect on disease So slows the joint

progression. destruction.
But Fast Acting. But Slow Acting.
Antirheumatic Drugs
 Classification of DMARDs

Conventional DMARDs Biological DMARDs

• Available since long time. • Formed by Biological methods
lie recombinant DNA
technology against some
particular target.
 CONVENTIONAL DMARDs
1. Methotrexate
2. Chloroquine/Hydrochloroquine
3. Azathioprine
4. Leflunomide
5. Sulfasalazine
 Methotrexate (Mtx)
• Immunosuppressant and anti-inflammatory property.
• Low dose 7.5-15 mg weekly Increase extracellular adenosine

Anti inflammatory property

• Onset of symptom relief is relatively rapid (3-6 weeks) therefore Mtx is
preferred for initial treatment.
• DMARD of first choice but can cause hepatotoxicity so LFT should
always be done.
 Azathioprine
• Acts after getting converted into 6-metacaptopurine.
• Less commonly used.
• Given along with corticosteroids, it has a steroid sparing effect
• Not combined with Mtx.
• Dose – 50-150 mg/day
 Sulfasalazine
• Compound of sulfapyridine and 5-amino salicylic acid.
• MOA is not known.
• Efficacy in RA is modest.
• Side effects may be unpleasant.
• Second line drug for milder cases or is combined with Mtx.
• Dose : 1-3 g/day in 2-3 divided doses.
 Hydrochloroquine/Chloroquine
• Antimalarial drugs found to induce remission in about 50% of RA
patients but take 3-6 months.
• Relatively low toxicity but efficacy is also low, bony erosions are not
prevented.
• MOA not known.
• For RA , to be given for long periods
• Dose : 400 mg/day for 4-6 weeks, followed by 200 mg/day for
maintenance.
 Leflunomide
• Inhibits proliferation of stimulated lymphocytes in patients with active RA.
• Arthritic symptoms are suppressed and radiological progression of disease
is retarded.
• Efficacy comparable to Mtx and onset of benefit is as fast as 4 weeks.
• Rapidly converted to active metabolite which inhibits dihydro-orotate
dehydrogenase and pyrimidine synthesis in actively divided cells.
• Dose : 100 mg daily for 3 days followed by 20 mg OD.
• Adverse effects : Diarrhoea, Headache, Nausea, Rahes, Loss of hair, etc.
 BIOLOGICAL DMARDs
1. TNF alpha Inhibitors
2. Etanercept
3. Infliximab
4. Adalimumab
 TNF alpha Inhibitors
• Mainly suppress macrophage and T-cell function.
• Inflammatory changes in the joint regress and new erosions are
slowed.
• Quicker response than non biological DMARDs.
• Generally added to Mtx when response to the latter is not
adequate.
 Etanercept
• Recombinant fusion protein of TNF-receptor with Fc portion of
human IgG1
• Dose and Route : Subcutaneous injection 50 mg weekly.
• Pain, redness, itching and swelling occurs at site of injection and
chest infections may be increased.
 Infliximab
• Monoclonal antibody which binds and neutralizes TNF alpha.
• Dose : 3-5 mg/kg is infused i.v. every 4-8 weeks.
• Fever, chills follow the infusion.
• Susceptibility to respiratory infections is increased and worsening of
CHF has been noted.
• Usually combined with Mtx which improves the response and
decreases antibody formation against infliximab.
 Adalimumab
• Recombinant human monoclonal Ab.
• Dose and Route : 40 mg subcutaneous every 2 weeks.
• Adverse Effects : Injection site reaction and respiratory infections.
• Combination with Mtx is advised to improve the response and
decrease antibody formation.
Thank you!