Remicade Infusion Therapy

Remicade is an entirely new type of drug for Crohn's disease... a real breakthrough. It is an antibody that blocks a substance called TNF. (TNF stands for "Tumor Necrosis Factor" - but this has nothing to do with tumors or cancer.) This newly discovered protein has been found in the blood of patients with active inflammation like Crohn's disease and Rheumatoid Arthritis. In Crohn's disease, it is felt that TNF plays an important role in causing inflammation and damage of the intestinal wall. In fact, evidence to date strongly suggests a central role for TNF in Crohn's disease. Overproduction of TNF may lead to a flare-up of Crohn's symptoms. Why this occurs is just some individuals is still a mystery.

A biological agent is a "designer molecule" made to hit a specific target. Remicade is a new biological agent that was made to target only TNF. It is co-produced in mice and the final product is about 75% human and 25% mouse antibody. Remicade helps control the symptoms of Crohn's disease by binding to TNF and neutralizing its action. Because Remicade blocks TNF in Crohn's patients, it is sometimes called an "anti-TNF antibody." Remicade was approved by the FDA in May 1998 for treatment of Crohn's disease. It was recently also approved to treat patients with Rheumatoid Arthritis whom also seem to have an excess amount of TNF in their joints.

Who should receive Remicade?

Remicade is currently reserved for patients with active signs and symptoms of Crohn's disease who fail to adequately control their disease with convential therapy - prednisone, Pentasa, Asacol, Imuran, etc.

How is Remicade administered?

Unlike most medications for Crohn's, Remicade is given as a solution by intravenous infusion (into a vein). This infusion may be given in your doctor's office, or at an infusion center, or in an outpatient setting your doctor selects. The actual infusion takes 2 hours. You should plan on spending about 3 hours, which includes preparation. During this time, the nurse will check on you at regular intervals. The infusion is not sedating and most patients are able to drive home. Current dosage recommendations are:

• For moderately to severely active Crohn's disease without fistulas, a single infusion is recommended

• For Crohn's patients with fistulas, three infusions (an initial infusion, then one 2 weeks later and one 6 weeks later) are recommended

What are the benefits of Remicade?

This is a new drug and there is much to learn - especially about the risks and benefits. Short term studies look promising. One recent study of 108 patients reported that 4 weeks after one dose, 82% of people who received the recommended dose had improvement in the signs and symptoms of their Crohn's disease, compared to only 16% of the people who received a placebo. Almost half experienced complete disappearance of their Crohn's symptoms at one month.

Healing of intestinal fistulas

Another indication for Remicade is to help close intestinal fisulas. Common in Crohn's disease, a fistula is simply an abnormal "tunnel" that makes a path between two body cavities - such as between intestine and vagina, intestine and bladder, or from the intestine and through skin. One way a fistula may form is from an abscess - a pocket of pus in the body. The abscess may be constantly filling with body fluids such as stool or urine, which prevents healing. Eventually the fistula breaks through to the skin, another body cavity, or an organ. Fistulas are more common in Crohn's Disease than in ulcerative colitis. Approximately 30% of people with Crohn's Disease develop fistulas.

Until Remicade, there really was no generally effective medical therapy to help close a fistula. Antibiotics work only sometimes and major surgery was often required. Recent information suggests that Remicade may be of benefit in this situation. One clinical study looked at the effects of Remicade on healing of fistulas in 94 patients with Crohn's disease. About 68% of patients receiving the recommended dose of Remicade had at least half of their fistulas close for at least 1 month, compared to 26% of people who received a placebo. About 55% of patients had all of their fistulas close for at least 1 month, compared to 13% of people who received a placebo.

Can you predict which patients will best respond to Remicade?

No. As you see above, not every patient responds to this medication. It would be helpful to predict in advance who will respond and who will not. There have been a number of attempts to determine which Crohn's patients will likely benefit. So far, initial studies have been unable to determine specific factors that would predict a beneficial response. The only way to find out is to try it.

What if I have a stricture in my small intestine?

Remicade probably won't help. The natural history of Crohn's disease is to form ulcers on the inner intestinal wall which heal and then return over and over. Each time an ulcer heals some scar tissue (fibrosis) is formed. This scar tissue can accumulate over time and cause a narrowing in the small intestine or colon. This is called a stricture. A significant percentage of individuals may develop intestinal obstruction, or "blockage of the bowels," from these strictures. Remicade works best in reducing active inflammation, but has little effect on scar tissue which may be permanent. Reports have demonstrated that individuals who have intestinal strictures are less likely to respond to Remicade.

How long does Remicade last

Remicade has been shown in medical studies to heal the lining of the intestine, a single dose has been shown to provide full benefit for only 8 to 12 weeks, on average. Still, about 20% of patients still show a positive effect at 44 weeks.

What are the side effects?

In medical studies, most people had no side effects related to Remicade. Remicade infusions are usually well tolerated. Immediate side effects occur in about 5% of patients and include headache, nausea, itching, stinging, dizziness, fatigue, and fever and did not last long. Only 2% of people had to stop the infusion because of side effects. The infusion-related reactions, if they occurred, were typically mild, requiring reduction of infusion rate, administration of acetaminophen, and/or Benedryl. Pretreatment with Tylenol and Benedryl may be of benefit.

Some patients develop antibodies to Remicade that may result, rarely, in the development of a lupus-like syndrome. Recent data show this to occur in less than 1% of patients. Symptoms included migratory joint pain, pleuritis, and rash. There were no kidney or central nervous system symptoms. These symptoms resolved by simply stopping treatment and a short couse of steroids.

You should not take Remicade if you have an acute or chronic infection.

Treatment with REMICADE should not be initiated in patients with an active infection, including clinically important localized infections. The risks and benefits of treatment should be considered prior to initiating therapy in patients:

• with chronic or recurrent infection;

• who have been exposed to tuberculosis;

• who have resided or traveled in areas of endemic tuberculosis or endemic mycoses, such as histoplasmosis, coccidioidomycosis, or blastomycosis; or

• with underlying conditions that may predispose them to infection.

Cases of reactivation of tuberculosis or new tuberculosis infections have been observed in patients receiving REMICADE, including patients who have previously received treatment for latent or active tuberculosis. Patients should be evaluated for tuberculosis risk factors and tested for latent infection prior to initiating REMICADE and periodically during therapy.

Treatment of latent tuberculosis infection prior to therapy with TNF blocking agents has been shown to reduce the risk of tuberculosis reactivation during therapy. Induration of 5 mm or greater with tuberculin skin testing should be considered a positive test result when assessing if treatment for latent tuberculosis is needed prior to initiating REMICADE, even for patients previously vaccinated with Bacille Calmette-Guerin (BCG).

Anti-tuberculosis therapy should also be considered prior to initiation of REMICADE in patients with a past history of latent or active tuberculosis in whom an adequate course of treatment cannot be confirmed, and for patients with a negative test for latent tuberculosis but having risk factors for tuberculosis infection. Consultation with a physician with expertise in the treatment of tuberculosis is recommended to aid in the decision whether initiating anti-tuberculosis therapy is appropriate for an individual patient.