Anakinra

Introduction:

Anakinra is an IL-1 receptor antagonist.

Action:
The treatment with this drug causes slowing of process of moderate to serious rheumatoid arthritis.

The drug may be used alone or in combination with other drugs.

Administration:
It is administered subcutaneously.

Adverse effects:
It may cause headache, nausea, vomiting and injection site reactions.

Adalimumab

Introduction:

It is a fully human recombinant monoclonal antibody (MAB).

Mechanism of action:
It gets bind to human TNF-α receptor site thus stops endogenous TNF- α activity by preventing its interaction with p55 and p75 cell surface receptors.

Action:
It decreases symptoms of Rheumatoid arthritis and stops erosion of the (bone) structure.

Therapeutic uses:
It is used in Rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis. (As increased TNF in the synovial fluid cause pain and joint destruction in Rheumatoid arthritis).

Pharmacokinetics:
It is used subcutaneously and its half life is 10-20 days.

Dose and Administration:
Its usual dose is 40 mg every other week. It is used Subcutaneously only.

Adverse effects:
It may cause headache, nausea, rashes and reactions at the site of injection.

Infliximab

Introduction:

It is a chimeric IgGκ monoclonal antibody made up of human (75%) and animals (25%) such as rats and mice.

Mechanism of Action:
Infliximab binds to human TNF-α and as a result neutralize the cytokines.

Action:
It removes the progression of damage or erosion to structure so that patient can perform functions more efficiently.

Pharmacokinetics:
It is administered intravenously and slowly in about 2 hour’s time in doses of 3 mg/kg to 10 mg/kg. Its half life is about 9-10 days. It is distributed equally in vascular compartments.

It is not approved for therapy continuously after 6th week.

Therapeutic uses:
It is used in Rheumatoid arthritis and Crohn’s disease. It has been found that the combination with methotrexate is more effective.

Adverse effects:
It may cause upper respiratory tract infections, nausea and vomiting. The production of anti-infliximab antibodies have also been studied after prolonged use of infliximab. It may cause some of the reactions at the site of infusion such as fever, chill and pruritis.

Leukopenia, neutropenia and thrombocytopenia have also been found.

Etanercept

Introduction:

Etanercept is a biotechnological product as it is genetically engineered fusion protein.
It is composed of:

1. Two identical chains of the recombinant human TNF-receptor p75 monomer.

2. Fc domain of IgG1 (human immunoglobulin).

These two are fused together.

Mechanism of action:

Etanercept binds two molecules of TNF thereby resulting in no binding of TNF to cellular receptors.

Action:
Etanercept, Infliximab and adalimumab decrease the activity of TNF. TNF is important for immunity system and must rest in the rheumatic synovium for the action to take place.

Pharmacokinetics:
It is given subcutaneously, 25 mg, two times a week. Maximum serum concentration is obtained within 72 hours after parenteral administration. Its half life is 4-6 days.

Therapeutic Uses:
Rheumatic and psoriatic arthritis.

Adverse effects:
No important adverse effects have been found.

Contraindications:
In serious type of infections like sepsis, etanercept should not be given to patient.

NOTE:
Etanercept and methotrexate are more effective when used together (than alone) in slowing the

1. Disease process

2. Improvement in function

3. Stoppage of the symptoms.

Anticytokine Therapies in Rheumatoid Arthritis

Anticytokines act on the proinflammatory cytokines i.e. interleukin-1b (IL- 1b) and Tumor necrosis factor- α (TNF- α).

Gold salts

Gold compounds are of two types:

1. Those used for intramuscularly such as gold sodium thiomalate and aurothioglucose. They are made up of about 50% elemental gold.

2. Those used in oral formulation such as auranofin containing 26-29% elemental gold.

Mechanism of action:
It is thought that these gold compounds are taken up by macrophages and thus suppresses the phagocytosis and lysosomal enzyme activity.

This process is responsible for the reduction of bone and articular destruction.

Pharmacokinetics:
They tend to accumulate in the synovial fluid and bone marrow. 1/3 of the gold compounds are excreted in the urine and remaining goes through feces.

Adverse effects:
Pruritic (itching) skin rashes may occur.

D-Penicillamine

It is a metabolite of penicillin and an analog of cysteine (an amino acid).


Action:
It slows the advancement of the bone erosion and rheumatoid arthritis.

Adverse effects:
It may cause some of the very serious effects such as some of the dermatologic problems, nephritis and aplastic anemia.