Ankylosing Spondylitis (AS) Medications

Ankylosing spondylitis is an inflammatory autoimmune disease and a rare form of arthritis. The condition tends to affect the sacroiliac joints between the bones of the pelvis, and the axial skeleton (the spinal column, ribcage, neck, and skull bones).

Ankylosing spondylitis (AS) is a type of arthritis that involves the spine, sacroiliac joints, and other joints such as the hips and shoulders. It is in a category of arthritis called spondyloarthropathy. Other spondyloarthropathies include reactive arthritis and psoriatic arthritis. Men develop ankylosing spondylitis three times more often than women do. People with ankylosing spondylitis develop the disease prior to age 45. Symptoms include the following:

• Frequent lower back pain
• Back stiffness first thing in the morning or after a long rest period
• Pain or tenderness of the ribs, shoulder blades, hips, thighs, and bony points along the spine
• Pain and tenderness in joints other than the spine may accompany the condition
• Eye pain, watery eyes, red eyes, blurred vision, and sensitivity to bright light (The disease sometimes affects the eyes and other organs.)

The precise cause of ankylosing spondylitis is unknown. Many people with ankylosing spondylitis have other family members with the disease. A gene marker known as human lymphocyte antigen (HLA) type B27 (HLA-B27) is found by blood testing in most individuals with ankylosing spondylitis, while it is also found in a small percentage of the general population. This blood test can aid in the diagnosis of ankylosing spondylitis.

Although AS predominantly affects the spine, it also can affect other joints such as the hips, the shoulders, and occasionally, other joints including the knees, ankles, feet, and hands. Ankylosing spondylitis may also affect other parts of the body besides the skeleton, such as the eyes, heart, and lungs. The prognosis is generally good, but long-term medications and physical therapy are needed to control pain and to maintain mobility.

Nothing cures ankylosing spondylitis, but people with the disease can lessen their pain and maintain their mobility. Medications are commonly prescribed to decrease pain and inflammation that causes joint swelling and may contribute to pain. Exercise is one of the most important activities for maintaining and restoring joint mobility, decreasing pain, and strengthening muscles to improve posture. A healthy diet and adequate sleep are important. Heat or cold may help alleviate symptoms. Applying heat helps relax aching muscles and reduces joint pain and soreness. Applying cold helps decrease pain and joint swelling. Bending and lifting properly (with the knees rather than with the back) and carrying heavy objects close to the body, when necessary, protect the joints and maintain function. Other therapeutic measures include sleeping flat on the back on a firm, supportive mattress and using a pillow that properly supports the neck.

Drugs in this class include diclofenac (Cataflam, Voltaren), ibuprofen (Advil, Motrin), ketoprofen (Orudis), naproxen (Aleve, Naprosyn), piroxicam (Feldene), etodolac (Lodine), indomethacin (Indocin), oxaprozin (Daypro), nabumetone (Relafen), and meloxicam (Mobic).

How NSAIDs work: NSAIDs prevent the body from producing prostaglandins, which have been identified as a cause of pain and inflammation. NSAIDs prevent this by inhibiting the cyclooxygenase (COX) enzymes that are important in the formation of prostaglandins by cells. Several types of anti-inflammatory agents exist. Doctors recommend NSAIDs as the first type of medicine to try after they initially diagnose ankylosing spondylitis. Some of these drugs may be purchased without a prescription.

• Who should not use these medications: People with the following conditions should not use NSAIDs:
  • Allergy to NSAIDs or aspirin
  • Peptic ulcer disease
  • Bleeding disorders
  • Kidney function impairment
  • Only certain NSAIDs should be used by people with conditions requiring treatment with blood thinners such as warfarin
• Use: NSAIDs are taken as oral tablets, as capsules, or as a liquid suspension in various dosage regimens. Take them with food to decrease stomach irritation.
• Drug or food interactions: NSAIDs may cause fluid retention, thereby decreasing the effectiveness of high blood pressure medications and diuretics (water pills). Phenytoin (Dilantin) or methotrexate (Rheumatrex) toxicity may increase when NSAIDs are used. Use with corticosteroids (for example, prednisone [Deltasone, Orasone]) or high doses of aspirin may increase the risk of developing peptic ulcers or gastrointestinal bleeding. Some NSAIDs interfere with the effects of aspirin taken to prevent heart disease.
• Side effects: NSAIDs must be used with caution in people with a history of peptic ulcer disease. By inhibiting prostaglandin formation in the GI tract, these NSAIDs may predispose these people to gastropathy, which can lead to stomach erosions, ulcers, and bleeding. NSAIDs can cause fluid retention and worsen some conditions such as heart failure, high blood pressure, kidney impairment, or liver impairment. Ask your doctor prior to using NSAIDs in pregnancy. Seek medical attention if any of the following occur:
  • Severe stomach pain
  • Bloody vomit
  • Bloody or black, tarry stools
  • Bloody or cloudy urine
  • Unexplained bruising or bleeding
  • Wheezing or breathing troubles
  • Swelling in the face or around the eyes
  • Severe rash or red itchy skin

A newer class of NSAIDs known as COX-2 inhibitors (or COXIBs, including Celebrex) reduces the risk of gastrointestinal complications and bleeding with NSAID therapy. However, the COX-2 inhibitors have been found to have their own potential, serious side effects, including an increased risk of heart attack, stroke, and heart failure. These risks may be present in varying degrees with all of the NSAIDs.

Drugs in this class that are most commonly prescribed for ankylosing spondylitis are methotrexate (Rheumatrex) and sulfasalazine (Azulfidine). These medications are generally used when NSAIDs are ineffective. Research has shown that these medications do not help significantly with spinal inflammation and work better on inflammation in the peripheral joints (such as the knees, hands and feet).

• How DMARDs works: This group includes a wide variety of agents that work in many different ways. They all interfere in the immune processes that promote inflammation.

Methotrexate (Rheumatrex)

• Who should not use these medications: People with the following conditions should not take methotrexate:
  • Allergy to methotrexate
  • Alcoholism
  • Liver or kidney failure
  • Immune deficiency syndromes
  • Low blood cell counts
  • Pregnant women should not take methotrexate as it is teratogenic (causes severe problems with the development of the baby).
• Use: Methotrexate is taken orally or as an injection once per week.
• Drug or food interactions: To lessen GI toxicity, daily administration of low-dose folic acid (1-2 mg) is recommended.
• Side effects: To guard against problems, kidney and liver function are monitored regularly, as are blood cell counts. Methotrexate may cause headache and toxic effects to blood, kidneys, liver, lungs, and gastrointestinal and nervous systems.

Sulfasalazine (Azulfidine)

• Who should not use these medications: People with the following conditions should not use sulfasalazine:
  • Allergy to sulfa drugs, aspirin, or aspirin-like products (NSAIDs)
  • Active peptic ulcer disease
  • Severe kidney failure
• Use: Sulfasalazine is taken orally in varying doses with food.
• Drug or food interactions: Sulfasalazine may decrease warfarin (Coumadin) absorption, thereby decreasing warfarin effectiveness. Sulfasalazine may increase the risk of bleeding when administered with other drugs that alter blood coagulation (for example, heparin [Hep-Lock]).
• Side effects: Sulfasalazine may cause the following:
  • Toxicity to blood cells
  • Nausea
  • Vomiting
  • Abdominal cramping
  • Constipation

Drugs in this class include etanercept (Enbrel), infliximab (Remicade), adalimumab (Humira), and golimumab (Simponi).

• How TNF inhibitors work: These agents inhibit key factors responsible for inflammatory responses in the immune system. Etanercept, infliximab, adalimumab, and golimumab are tumor necrosis factor (TNF) antagonists. TNF is a naturally occurring chemical which promotes inflammation in the body. TNF antagonists block TNF and therefore decrease inflammation.
• Who should not use these medications: People with severe heart failure, an active infection, sepsis, or active tuberculosis should not take the drug. Patients with a skin test positive for tuberculosis or a history of histoplasmosis should undergo treatment to reduce the reactivation of these infections.
• Use: Etanercept is taken as a subcutaneous (under the skin) injection once or twice a week. Adalimumab is taken as an injection twice a month. Golimumab is taken as an injection once a month. Infliximab is taken as a two hour intravenous infusion. This may be given in a doctor's office, the hospital, or another outpatient facility. It is infused every eight weeks, after more frequent doses initially. All of the TNF inhibitors may be used alone or with methotrexate or sulfasalazine.
• Drug or food interactions: TNF inhibitors may increase infection risk or decrease blood cell counts when used with other immune modulators or immunosuppressant drugs (for example, anticancer agents, corticosteroids). Immunization with some vaccines may not be effective.
• Side effects: TNF inhibitors must be used with caution in people with heart failure or impaired kidney function. If a serious infection develops, the drug must be discontinued. Exacerbation of tuberculosis, infection with unusual organisms, and the rare development of drug-induced lupus are other rare but serious side effects. The following are other possible adverse effects:
  • Etanercept, adalimumab and golimumab sometimes cause injection site pain, redness, and swelling.
  • Reactions to the intravenous infusion of infliximab may occur such as shortness of breath and hives.
  • Fever
  • Rash
  • Cold or flu symptoms
  • Stomach upset
  • Nausea
  • Vomiting

Drugs in this class include prednisone (Deltasone, Orasone), methylprednisolone (Solu-Medrol, Depo-Medrol), betamethasone (Celestone, Soluspan), cortisone (Cortone), dexamethasone (Decadron), prednisolone (Delta-Cortef), and triamcinolone (Aristocort).

• How corticosteroids work: These drugs decrease swelling and inflammation by suppressing immune response.
• Who should not use these medications: People with the following conditions should not use corticosteroids:
  • Allergy to corticosteroids
  • Active infections caused by viruses, fungi, or Mycobacterium tuberculosis
  • Active peptic ulcer disease
  • Liver impairment
• Use: Corticosteroids can be taken in various ways (by mouth, intravenously, intramuscularly or intra-articularly (injected directly into a joint). The goal is to use the smallest dose that controls symptoms. The length of treatment should be as short as possible in order to decrease the risk of developing side effects. When taken orally, take with food to decrease stomach upset. Corticosteroids are generally not used as long-term medications in ankylosing spondylitis due to the risk of side effects such as injury to bone (see below).
• Drug or food interactions: Many drug interactions are possible, therefore, consult with a doctor or pharmacist before taking new prescription or over-the-counter medications. Aspirin, NSAIDs, such as Advil or Aleve, or other drugs associated with stomach ulcers may increase the risk of developing stomach ulcers. Corticosteroids may decrease potassium levels and must be used with caution with other drugs that decrease potassium levels (for example, diuretics such as Lasix).
• Side effects: Ideally, corticosteroids are used in low doses only long enough to bring sudden flares in symptoms under control. Long-term use is associated with serious side effects, such as osteoporosis, osteonecrosis, glaucoma, cataracts, mental changes, abnormal blood glucose levels and diabetes, or arrested bone growth in children who are prepubescent. After prolonged use, the corticosteroid dose must be gradually decreased over weeks to months to avoid corticosteroid withdrawal syndrome.