Disease-modifying antirheumatic drugs

Types and differences of DMARDs

The most common types of disease-modifying antirheumatic drugs (DMARDs) used to treat pain conditions are:

The most commonly administered DMARDs include:

• Methotrexate (Folex, Rheumatrex, Trexall). Regularly used to treat cancer and psoriasis. Methotrexate is also the most commonly used DMARD for rheumatoid arthritis (RA). It reduces inflammation by obstructing how the body metabolizes folic acid. It can be given orally or injected. Long-term use can damage the liver, making routine tests of liver function necessary. Use of alcohol should be avoided when taking methotrexate. Recent research suggests that use of methotrexate may prevent undifferentiated (generalized) arthritis from escalating to RA.
• Hydroxychloroquine (Plaquenil). Originally used to treat malaria, hydroxychloroquine is also used for patients with RA. Taken orally, hydroxychloroquine suppresses the immune system’s reaction to RA that causes pain and inflammation. Eye exams may be given about every six months because visual impairment is a rare side effect of the drug. Visual impairment usually occurs at higher doses, and the doses used these days are substantially low.
• Sulfasalazine (Azulfidine). A combination of salicylate and an antibiotic. Sulfasalazine blocks inflammation and restrains bacteria growth and is given in liquid or tablet form. It is most commonly used to treat inflammatory bowel disease, but also for other conditions, such as RA, psoriatic arthritis and ankylosing spondylitis. The most common side effect is nausea and abdominal pain. It can also increase sensitivity to sunlight.
• Methotrexate (Folex, Rheumatrex). Regularly used for cancer and psoriasis treatment. Methotrexate is also the most commonly used DMARD to treat RA. It reduces inflammation by obstructing how the body metabolizes folic acid. It can be given orally or injected. Long-term use can damage the liver, making routine tests of liver function necessary. Use of alcohol should be avoided when taking methotrexate.
• Leflunomide (Arava). The only DMARD specifically developed for the treatment of RA. Given orally, leflunomide may reduce pain and inflammation associated with RA. Leflunomide may also be used to treat certain cancers, such as leukemia.
• Gold salt compounds: auranofin (Ridaura), aurothioglucose (Solganal), aurothiomalate or gold sodium thiomalate (Aurolate, Myochrysine). Rarely used to treat RA and other diseases (e.g., psoriatic arthritis). Gold salt compounds can be injected or taken orally. How they work is unclear, but they are believed to interfere with white blood cells which cause joint damage and inflammation. Gold compounds cannot reverse pre-existing joint damage or deformities. Regular blood and urine tests are often given to monitor for possible serious side effects, including kidney problems.
• Penicillamine (Cuprimine, Depen). A distant relative of the antibiotic penicillin. Given orally, penicillamine is rarely used to treat RA. Penicillamine is thought to change the function of white blood cells that cause damage in joints. However, the mechanism through which this occurs is unclear. Penicillamine may be given along with nonsteroidal anti-inflammatory drugs (NSAIDs) in some cases. Gold salt compounds and penicillamine should not be taken together because of increased risk of side effects to the kidneys.
• Cyclosporine and azathioprine (Sandimmune, Neoral and Imuran). Originally manufactured to prevent rejection of transplanted organs by suppressing the immune system. These drugs may also be used to treat RA in some cases.

Other DMARDs include chlorambucil (Leukeran) and cyclosphosphamide (Cytoxan), which are used mainly to treat cancer, and mycophenolate (CellCept), which is used mainly to prevent rejection of a transplanted organ. They may sometimes be prescribed for severe renal or other organ disease.

Tumor necrosis factor (TNF) inhibitors such as adalimumab (Humira), etanercept (Enbrel) and infliximab (Remicade) are sometimes grouped in with DMARDs but generally are considered to be part of a related class of immunosuppressive drugs called biologic response modifiers (BRMs). They also treat conditions such as RA and psoriatic arthritis, and their benefits and risks may be similar to those of DMARDs.

Conditions treated with DMARDs

Disease-modifying antirheumatic drugs (DMARDs) may be used independently or in combination with other drugs to treat various diseases, including:

• Rheumatoid arthritis (RA). A chronic, inflammatory disease that causes the body’s immune system to attack the joints. This is by far the most common disease treated with DMARDs.
• Psoriatic arthritis. A form of arthritis that develops in some people with the skin disease psoriasis.
• Felty’s syndrome. Associated with RA. Felty’s syndrome occurs when a person with RA also has an enlarged spleen (splenomegaly) and an unusually low white blood cell count.
• Palindromic rheumatism. Intermittent episodes of arthritis. Individuals with this rare disease have repeated arthritic attacks but without producing irreversible changes in the joints.
• Ankylosing spondylitis. A rare, painful form of arthritis that affects the spine, causing bones to grow together. DMARDs may be prescribed to treat pain and inflammation.
• Scleroderma. A rare disease that causes hardening and tightening of skin and connective tissues. DMARDs may be used to treat symptoms of scleroderma, such as joint pain or stiffness, curling and pain or numbness in fingers.
• Systemic lupus erythematosus. A chronic autoimmune disorder in which natural antibodies attack several systems of the body. DMARDs may help treat and alleviate pain and inflammation from attacks of lupus. DMARDs can also address the kidney damage that can result from lupus or other conditions.
• Colitis. Inflammation of the colon with symptoms that include abdominal pain and cramps. DMARDs may help treat this condition.
• Cancer pain. DMARDs can help treat and alleviate pain associated with some cancers, including leukemia and lymphoma. And the primary use of some DMARDs is to fight the cancer itself.

As immunosuppressants, DMARDs are also used to prevent rejection of transplanted organs.

Conditions of concern

Disease-modifying antirheumatic drugs (DMARDs) each have different chemical properties. Accordingly, DMARDs may respond differently depending on the condition being treated, the drug being used, the dosage and characteristics of the patient.

In general, patients are encouraged to drink a lot of fluids to increase urine output. Prolonged exposure to sunlight should be avoided when DMARDs are prescribed, including the use of a highly protective sunscreen. In addition, because DMARDs may affect the immune system, proper oral hygiene will help prevent mouth infections from occurring.

Potentially serious side effects or reduced effectiveness of DMARDs may occur in patients with any of the following conditions:

• DMARD allergies
• Alcoholism
• Bone marrow or blood toxicities
• Pregnancy or breastfeeding
• Uncontrolled high blood pressure
• Dermatitis
• Kidney or liver damage, including hepatitis
• Uncontrolled diabetes
• Colitis
• Cancer

Potential side effects of DMARDs

The potential benefits of disease-modifying antirheumatic drugs (DMARDs) should be weighed against possible side effects. The condition being treated will influence the choice and dosage of DMARDs. A physician should be consulted regularly during any treatment program involving DMARDs.

Patients who regularly use DMARDs are often carefully monitored for side effects in several ways, such as blood tests, urine tests, eye exams and chest x-ray. Depending on the disease, the DMARDs prescribed and the overall condition of the patient, certain side effects may occur. They include:

• Stomach pain, diarrhea or constipation
• Nausea or vomiting
• Headache
• Joint pain or swelling
• Skin rash
• Increased sensitivity to sunlight
• Mouth or throat sores
• High blood pressure
• Increased vulnerability to infection, including in the eyes
• Cold or flu-like symptoms, such as fever
• Hair loss
• Low blood count, low white blood cell count

Rheumatoid arthritis (RA) has been linked to increased risk of developing lymphoma. Some studies have suggested that this could be due to use of certain DMARDs, but recent research indicates that the inflammation of RA may account for the cancer risk and that the medications do not appear to be a factor, with the possible exception of azathioprine, which is seldom used to treat RA.

Drug or other interactions

Many drug interactions with disease-modifying antirheumatic drugs (DMARDs) exist. Patients are encouraged to consult a physician before taking any additional prescriptions, over-the-counter medications, nutritional supplements or herbal medications.

Patients are advised to discuss with a physician whether vaccines should be administered when taking DMARDs. In addition, several DMARDs may cause an increase in sun sensitivity. Eating grapefruit or drinking the juice should be avoided before or after taking the DMARD cyclosporine. Recent research also suggests that pomegranate juice may affect some medications like grapefruit juice does. Use of antacids at the same time as sulfasalazine is not recommended.

Some types of medication may reduce the effectiveness or cause side effects in patients taking DMARDs, depending on the situation of the patient. They include:

• Antibiotics, antifungals and antivirals
• Anticonvulsants
• Birth control pills (oral contraceptives)
• Heart medications
• NSAIDs, including aspirin, ibuprofen and naproxen
• Tuberculosis drugs

Blood pressure, kidney function and liver function are often monitored regularly to protect against side effects. Long-term DMARD therapy in children and pregnant women is usually discouraged. In addition, DMARDs may not be appropriate for patients who have recently undergone radiation therapy.

Pregnancy, child and elderly use issues

Disease-modifying antirheumatic drugs (DMARDs) may harm fetal development. Consequently, sexually active men and women using DMARDs should use effective means of contraception during every sexual encounter. In most cases, women who are pregnant or breastfeeding or who may become pregnant are advised not to take DMARDs.

In addition, it is important to note that some DMARDs may decrease the effect of birth control pills (oral contraceptives). Patients using these contraceptives are advised to ask their physician about alternate methods of birth control.

DMARDs are acceptable for children in certain circumstances, such as juvenile rheumatoid arthritis or organ transplantation, but children are monitored closely for possible side effects. Occasionally, lower doses of DMARDs may be required for elderly individuals. However, they generally are at no greater risk for side effects than younger adults.