Introduction

Medications play an important role in the care of most people with systemic lupus erythematosus (SLE). This pamphlet (see Table 1 on page 5) discusses the principal drugs used in the primary management of lupus:

• Anti-inflammatory drugs
• Corticosteroids
• Anti-malarials
• Cytotoxic, or immunosuppressive, drugs
• Investigational (research) drugs:
  • hormone modifications
  • more selective immunosuppressive drugs
  • biologic agents.

Which Medications Are Right For My Lupus?

The choice of drugs is highly individualized and typically changes often during the course of the disease. Factors that are considered in treatment decisions include:

1. the type and severity of lupus symptoms
2. the person's response to treatment
3. risks of drug side effects.

In addition, it is important to note that people with lupus often require other drugs for the treatment of conditions commonly seen with the disease. Examples of these types of medications include:

• diuretics for fluid retention
• anti-hypertensive drugs for increased blood pressure
• anti-convulsants for seizure disorders
• antibiotics for infections
• drugs for osteoporosis.

Anti-Inflammatory Drugs

Anti-inflammatory drugs relieve the symptoms of lupus by reducing the inflammation responsible for the pain and discomfort.

• Anti-inflammatory medications are the most commonly used drugs for lupus treatment, particularly for symptoms such as:
  • fever,
  • arthritis, or
  • pleurisy
• Improvement in symptoms is generally noted within several days of beginning treatment.
• In the majority of people with lupus, anti-inflammatory drugs are the only medication that is ever required to control their lupus.

Anti-inflammatory drugs fall into two categories (see Table 1 on page 5)
     1. non-steroidal anti-inflammatory drugs
     2. corticosteriods

Non-Steroidal Anti-inflammatory Drugs

The NSAIDs include both salicylates (aspirin) and related drugs that may be purchased over the counter (brand names: Advil, Nuprin, Aleve) or that require a physician's prescription.

When Should My Doctor Prescribe NSAIDs?

NSAIDs are especially useful for:

• musculoskeletal symptoms, such as arthritis, arthralgia, joint stiffness or pain
• fever and chest pain from mild pleurisy (inflammation of the lining of the lung)
• pericarditis (inflammation of the sac around the heart).

For reasons that are not known, people often respond better to one non-steroidal drug than another, and it may be necessary to try courses of several different drugs to determine the most effective one.

NSAID Side Effects

• The most common side effect of non-steroidal medications is irritation of the stomach, which causes abdominal pain.
• Infrequently, this may lead to serious complications such as an ulcer with bleeding.
• To reduce the chance of these problems, non-steroidal drugs are usually taken with meals or given along with other medications that protect the stomach. A new class of NSAIDs called C ox-2 inhibitors which include Celebrex, Vioxx, and Bextra have a lower risk of gastrointestinal complications.
• Recently, data from several clinical studies has raised concern regarding potential increased health risks associated with the use of prescription COX-2 selective, non-steroidal anti-inflammatory drugs (NSAID), such as Celebrex, Bextra, Vioxx and Aleve.  In late September, 2004, Merck & Co., Inc. announced a voluntary withdrawal of rofecoxib (Vioxx) from the U.S. and worldwide market due to safety concerns of an increased risk of cardiovascular events (including heart attack and stroke) in patients on rofecoxib. The LFA suggests that individuals who are taking these drugs and have concerns about their risks for complications should consult with their physician. 
• Occasionally, side effects from non-steroidal drugs may be mistaken for signs of active lupus:
  • fever
  • skin rashes
  • abnormal urine studies
  • severe headache.

Recognize of these complication of NSAID is important since the symptoms are promptly reversed simply by stopping the drug.

Corticosteroids (Cortisone)

Corticosteroids are naturally occurring hormones with very potent anti-inflammatory properties.

• In high doses, corticosteroids also suppress immune functions.
  • They may be used as creams or ointments for lupus skin rashes.
  • They may be given as pills or injections.
• Most signs of lupus respond rapidly to corticosteroid treatment.
• At times, treatment with corticosteroids may actually be life-saving.

When Should My Doctor Prescribe Corticosteroids?

The decision to begin corticosteroids, and the details as to what type and dose of corticosteroid to use, are highly individualized:

• If a person with symptoms such as fever, arthritis, or pleurisy that has not responded to non-steroidal drugs, that might be treated with low doses of an oral corticosteroid, such as prednisone or methylprednisolone (brand name: prednisolone).
• Individuals with more severe or serious lupus symptoms, such as kidney disease, seizures, anemia, or low platelets (thrombocytopenia) may require high doses of corticosteroids.
• In most instances, the corticosteroid is given as a single dose in the morning.
• Other ways of giving corticosteroids include:
  • Doses given several times each day
  • Doses only on alternate days
  • Injections
  • High doses given intravenously (called bolus therapy).

How Long Will I Take Corticosteroids?

Once the symptoms of lupus have responded to treatment, the dose of corticosteroids is gradually reduced (tapered). Meanwhile the individual is carefully watched worsening (relapse) of the disease.

• The longer a person has been on corticosteroids, the more difficult it generally becomes to lower the dose.
• It is very important that corticosteroids are taken exactly as prescribed.
• Treatment should never be stopped abruptly without consulting with a physician.

Corticosteroid Side Effects

There are many complications of corticosteroid treatment, and the risks of these complications are increased when:

1. high doses of corticosteroids are required
2. corticosteroids are used for an extended period.

Corticosteroids may:

• produce changes in physical appearance:
  • weight gain
  • puffy cheeks
  • thinning of the skin and hair
  • easy bruising.
• cause stomach discomfort such as dyspepsia or heartburn.
  • These may be minimized by giving the drug with meals or along with medications that prevent stomach damage.
• Cause marked changes in mood, including:
  • depression
  • mood swings.
• Cause diabetes.
• increase the risk of infections, muscle weakness, or cataracts.
• have an effect on the bones including:
  • joint damage of the hips, knees, or other joints (osteonecrosis or avascular necrosis).
• produce osteoporosis (thinning of bone) when given over long periods.
  • In most people, calcium or other medications to prevent osteoporosis are given along with the corticosteroids.

Anti-Malarial Drugs

Drugs used for the treatment of malaria are widely used in the management of lupus symptoms.

• The drug hydroxychloroquine (brand name: Plaquenil) is the most commonly used of the anti-malarial agents.

When Should My Doctor Prescribe Anti-Malarials?

• Anti-malarials are particularly effective in the treatment of:
  • lupus arthritis
  • skin rashes
  • mouth ulcers.
• Other possible benefits of anti-malarials include:
  • reducing the risk of blood clots
  • lowering cholesterol levels.
• Anti-malarials are considered to have a small risk of causing birth defects.
• Anti-malarials are generally not recommended for women who want to become pregnant.

Anti-malarial Side Effects

Low-Dose Therapy

• abdominal symptoms (stomach pain or dyspepsia)
• rashes or darkening of the skin
• muscle weakness
• shortly after starting treatment, there may be a temporary mild blurring of vision, which resolves on its own.

High-Dose Therapy

• In high doses (such as those used in the treatment of malaria), certain anti-malarial drugs may damage the retina of the eye, causing vision problems.
• With the low doses of anti-malarials used in the treatment of lupus, the risk of this complication is extremely low.
• However, as a precaution, people treated with anti-malarials generally have a thorough eye examination before the drug is started, and then every 6-12 months during therapy.
  • This screening is done so that any sign of damage to the retina can be detected early and, if needed, the drug can be stopped.

Cytotoxic , or Immunosuppressive Drugs

These drugs are used are used to suppress the immune system in people with lupus. The most commonly used drugs of this type are azathioprine (Imuran), cyclophosphamide (Cytoxan), and methotrexate (Rheumatrex), and cyclosporine (Sandimmune, Neoral) . These drugs are generally reserved for people with more serious manifestations of lupus such as — lupus kidney disease ( nephritis ), or or acute neurologic complications disease— in who have failed m treatment with corticosteroids . has failed.

When Should My Doctor Prescribe Immunosuppressive Drugs?

• These drugs are generally reserved for people with more serious manifestations of lupus, such as lupus nephritis or neurologic disease, in whom treatment with corticosteroids has failed.
• It is very important that immunosuppressive cytotoxic drugs only be given by physicians who are experienced with the use of these medications. The possible toxicities of these cytotoxic drugs are considerable and individuals treated with these drugs must be very carefully monitored. Some of these The drugs have a n major effect on cells produced by the bone marrow, including white blood cells, red blood cells, and platelets. Thus, people treated with immunosuppressive cytotoxic drugs must have regular complete blood counts (CBCs) to make certain that levels of these cells do not become too low. In addition, immunosupressive cytotoxic drugs reduce a person's ability to fight off infections. Those receiving cytotoxic immunosupressive drugs are more likely to contract viral infections such as shingles (herpes zoster), and other more serious infections may also develop.

Immunosuppressive Side Effects

The possible toxicities of cytotoxic drugs are considerable and individuals treated with these drugs must be very carefully monitored.

• The drugs have a major effect on cells produced by the bone marrow, including:
  • white blood cells
  • red blood cells
  • platelets.
• Thus, people treated with cytotoxic drugs must have regular complete blood counts (CBCs) to make certain that levels of these cells do not become too low.
• In addition, cytotoxic drugs reduce a person's ability to fight off infections.
• Those receiving cytotoxic drugs are more likely to contract viral infections such as shingles (herpes zoster)
• Other more serious infections may also develop.

Specific Toxicities

There are distinct toxicities that are unique to each cytotoxic immunosupressive drug. Cyclophosphamide, for instance, may cause hair loss, bladder complications, and sterility. Azathioprine may cause an allergic-type of hepatitis and pancreatitis. Methotrexate may cause liver damage, including cirrhosis, as well as a serious lung toxicity. Cyclosporine commonly produces hypertension and may lead to kidney damage. All cytotoxic immunosupressive drugs are thought to increase a person's risk for developing cancer.

Investigational Drugs

A number of investigational (research) drugs for lupus are currently being studied in clinical trials. Promising new treatments include hormone modifications, more selective immunosuppressive drugs, and biologic agents.

Researchers are studying biologic agents to selectively block pathways of the immune system from forming autoantibodies involved in the inflammation and damage that occurs in lupus. This is a new and exciting approach for both treating and preventing the disease.