In this essay we will discuss about the drugs used for the treatment of Rheumatoid Arthritis (RA).
NSAIDs are used as the initial therapy for RA and as an adjunct to DMARDs to provide symptomatic relief for pain and inflammation. They do not prevent the degenerative changes and tissue damage responsible for the deformity.
Glucocorticoids are not only anti-inflammatory but are also immunosuppressant’s. They relieve the symptoms and control the degenerative process of RA. However, their continuous use is associated with serious side effects.
Glucocorticoids, nevertheless, are still used in lower doses for symptomatic relief while waiting for a response to a slow acting DMARD, persistent synovitis despite adequate trials of NSAIDs and DMARDs and for severe constitutional symptoms (fever and weight loss) or extra-articular disease (vasculitis, episcleritis, or pleurisy).
Prednisone (orally) and methylprednisolone (IV) are generally preferred, because of cost and half-life considerations. Adverse effects are dose related and duration of the treatment and except for cataract and osteopenia, can be minimized by alternate day administration, once the disease is controlled.
3. Disease Modifying Antirheumatic Drugs (Dmards):
DMARDs are immunomodulatory and immunosuppressive drugs and include a large number of pharmacologically diverse agents that exert anti-inflammatory as well as immunosuppressive effects and retard the progression of bony erosions and cartilage loss. They are characterized by a delayed onset of action (may take up to 6 months to produce a full response) and the potential for serious toxicity.
The main drugs in this class are:
d. Biologic DMARDs
e. Other DMARDs
Gold salts and penicillamine are no longer because of their low therapeutic index.
Hydroxychloroquine, an antimalarial drug, appears to be of some benefit in treating the morning stiffness and joint pain of rheumatoid arthritis and also in the skin lesions of lupus erythematosus. The beneficial effects are not evident until about 1 month after initiation of therapy.
It is the drug of initial choice in very mild RA. It probably acts by blocking the production of inflammatory mediator and by interfering with the actions of leucocytes. It also inhibits the proliferation of lymphocytes. Side effects with prolonged treatment may result in corneal opacities and more seriously, retinal damage. It is contraindicated in pregnancy.
Sulfasalazine, another DMARD, is used as the initial choice in very mild RA. It takes about 3 months to produce its full therapeutic effect. Side effects include hematologic and liver toxicity and necessitate regular blood counts and liver function tests.
Methotrexate, a folic acid antagonist cytotoxic, is the initial choice for moderate to severe RA. It acts more rapidly, and if given in relative low doses is better tolerated, provided renal functions are normal. Concomitant use of folic acid may reduce methotrexate toxicity without impeding its efficacy. The main adverse effects are GI disorders, bone marrow suppression, liver cirrhosis and pulmonary fibrosis. Methotrexate is teratogenic and is contraindicated in pregnancy. It should be avoided in patients with significant hepatic or renal impairment.
d. Biologic DMARDs:
The term biologic is used for genetically engineered proteins that interact with protein of the body that mediate disease producing reactions. Biologic DMARDs neutralize one of the cytokines-tumour necrosis factor α (TNF-α) or interleukin-1α (IL-1), that are the prime activator of the inflammatory response. Cytokines are non- antibody proteins released by specific cells which on contact with specific antigen act as intracellular modulators in the generation of an immune response.
Tumour necrosis factor (TNF) inhibitors comprise etanercept and infliximab. Etanercept is a protein that resembles the cellular receptor to which TNF-α normally binds to exert its effects. Etanercept binds to TNF-α, blocking its interaction with cell surface receptors, thus inhibiting the inflammatory and immune-regulatory properties of TNF.
Infliximab is an antibody raised against TNF-α and when injected it binds to it and renders it inactive.
Inhibitors of interleukin -1 (IL-1)
Anakinra is a recombinant form of the naturally occurring IL-1 receptor antagonist that is used for RA. It blocks binding of IL-1 to its receptor, thus inhibiting the pro-inflammatory and immuno-modulatory actions of IL-1.
These drugs are used in patients with moderate to severe RA who do not respond to one or more DMARDs listed above. They have similar efficacy and toxicity profile. They are given by injection. These drugs act faster and slow degenerative changes better than other DMARDs, but their use is associated with serious side effects. The most serious side effect is infection and sepsis, which may be fatal. These drugs are contraindicated in patients with acute or chronic infections or with a history of recurrent infection.
e. Other Dmards:
Azathioprine, cyclophosphamide or cyclosporines are at times combined with methotrxate for treatment of severe RA. Combination therapy may lead to synergistic or unexpected toxicities and require proper precautions.