viernes, 22 de febrero de 2019

Disease-Modifying AntiRheumatic Drugs (DMARDs)

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By Ananya Mandal, MDReviewed by April Cashin-Garbutt, MA (Cantab)

Rheumatoid arthritis (RA) is an inflammatory disease that can affect up to 1% of the adult population. There is wide spread inflammation and sometimes severe crippling joint damage.

The condition is not curable but there is a class of drugs that are called Disease-Modifying AntiRheumatic Drugs (DMARDs) that can help in slowing the progression of the disease and prevent progressive joint damage, deformity and destruction.

The American College of Rheumatology (ACR) recommends DMARDs for nearly all RA patients within 3 months of diagnosis. The drugs can not only reduce joint damage, preserve joint structure and functions but also reduce the symptoms, improve quality of life and reduce healthcare costs.

How to choose a DMARD

There is an array of drugs available as DMARDs. Both oral and injectable DMARDs are available. Individual features of the patient determine the choice of the DMARD. The drug is chosen based on three important criteria:-

Duration of the symptoms - this is divided into three categories – less than 6 months, 6 to 24 months and more than 24 months
Active disease intensity – the disease may be low, moderate or highly active
Predicted outcome or prognosis – this is derived from several indices. Poor prognosis usually means limitation of functions, RA affecting organs other than joints, rheumatoid factor positivity, positive anti-cyclic citrullinated peptide antibodies, erosions of joints etc.

DMARDs

The DMARDs may take weeks to month to become effective. Some of these include;

Methotrexate

This drug acts by interruption of adenosine and inflammatory cell pathways. The dose is usually 10 mg/week, and increased to 20 mg/week, given as pills or by subcutaneous injection.

The action of the drug usually takes 4 to 6 weeks to come in. Many patients may be given corticosteroids in addition to reduce inflammation until the action of Methotrexate begins.

The possible side effects can be avoided by concomitant use of folic acid. Side effects include liver damage, interstitial pneumonitis, and bone marrow depression leading to anemia, risk of cancers like lymphomas and risk of damage to the unborn fetus if taken by pregnant mothers.

Sulfasalazine

This is one of the more effective DMARDs (less than methotrexate). This agent can slow the X ray evidenced joint damage. It is also given in combination with methotrexate and hydroxychloroquine as a triple therapy.

The dose is usually 2-3 gm per day given twice daily. The time taken for the action to come in may be 6 weeks to 3 months. Side effects include allergic reactions especially in those patients who are allergic to sulfa drugs.

Hydroxychloroquine

This is a derivative of Chloroquine that is an anti-malarial drug. Hydroxychloroquine is sometimes combined with methotrexate. Both give additional benefits to the patient. Hydroxychloroquine may also be part of triple therapy with Methotrexate and sulfasalazine.

The drug acts by modifying the innate immunity. The usual dose is 400 mg/day but 600 mg/day is sometimes used. The action of drug begins after around 2 to 4 months of use. If there is no response to the drug after 5 to 6 months, the drug is considered to be a failure.

Important side effects include deposition in the cornea and blurring of vision, eye muscle weakness, increase sensitivity to light, retinopathy that may lead to loss of vision.

Leflunomide

This is another effective DMARD. This agent acts by inhibiting de novo pyrimidine biosynthesis through the inhibition of the enzyme dihydroorotate dehydrogenase.

The usually used dose is 100mg daily for three days followed by20 mg daily. The dose may be reduced to 10mg if there are side effects. The action starts after 4 to 8 weeks of use. Leflunomide causes liver damage, gastrointestinal upset, loss of hair etc.

Gold salts

Two injectable gold compounds are available (Myochrysine and Solganal). An oral gold compound (Auranofin) is also available. These are rarely used these days because of their side effects and lack of effectiveness.

The injectable compounds are started at 10 mg intramuscular injections and then 50mg weekly until response is seen. The effects are seen after 4 to 6 months of use. Gold compounds cause severe side effects including rash, liver damage etc.

Azathioprine

This is an immunomodulatory drug used in RA. The drug may take 8-12 weeks to be effective. Side effects include bone marrow suppression and lowering of blood cell counts, kidney damage etc.

Cyclosporine

This is also an immunomodulatory drug that can be used in RA. It can be used in combination with methotrexate. Cyclosporine inhibits T cell function by preventing transcription of interleukin-2. Side effects include vulnerability to infections, raised blood pressure and kidney damage.