Tumor necrosis factor (TNF) antagonists for inflammatory bowel disease
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How It Works
A tumor necrosis factor (TNF) antagonist is a type of antibody that inhibits tumor necrosis factor, a protein that increases inflammation in the body. Infliximab, adalimumab, certolizumab, and natalizumab block the inflammatory response that happens in Crohn's disease and ulcerative colitis. They are given as a shot. Infliximab and natalizumab are given as a shot in a vein (intravenous, or IV). Adalimumab and certolizumab are given as a shot under the skin (subcutaneous).
Why It Is Used
Infliximab was first used to treat abnormal connections (fistulas) between the intestines and organs in moderate to severe Crohn's disease. Now it is used to induce and maintain remission (a period without symptoms) in people who have Crohn's disease or ulcerative colitis that has not improved with other medicines.
Adalimumab, certolizumab, and natalizumab are used to induce and maintain remission in people with Crohn's disease who have not improved with other medicines and who no longer respond to or cannot tolerate treatment with infliximab.
How Well It Works
Infliximab can induce remission in people with moderate to severe Crohn's disease, including the closing of fistulas. In one study, some people who were treated with infliximab had symptoms that came back after 3 months. It is now recommended that people treated with infliximab continue to get the medicine at regular intervals. This is called maintenance therapy.
In multiple studies, almost 70% of people taking infliximab had fewer symptoms or had healed fistulas.1
Adalimumab has shown promise in treating Crohn's disease in multiple studies.2 It works like infliximab and may be good for people who are allergic to infliximab.
Studies show that natalizumab works to stop the symptoms Crohn's disease in some people and to keep some people free of symptoms. But natalizumab may cause a serious and life-threatening disease called PML. Because of this risk, natalizumab is only available through a special prescription drug program.5
In one study, between 60% and 70% of people with ulcerative colitis were better 8 weeks after getting infliximab treatment. In another study, twice as many people got better after receiving infliximab compared to those taking a placebo.6
The long-term effectiveness and safety of these medicines are still being studied.
The most common side effect of TNF antagonists is an allergic reaction to the injection (shot) or infusion (medicine given in a vein—intravenously, or IV). If you have a reaction to the shot or infusion, it will happen right away, either during the infusion or within 1 to 2 hours after the infusion or shot. Your doctor may give you medicines to prevent or stop the reaction.
Symptoms of a shot or infusion site reaction include:
- Chest pain.
- Shortness of breath.
- Itching (pruritus).
- Heat and redness (flushing) in the face.
Warnings about serious side effects of TNF antagonists have been issued. The U.S. Food and Drug Administration (FDA) and the drug’s manufacturers have warned about:
- An increased risk of a serious infection. TNF antagonists affect your body's ability to fight all infections. So if you get a fever, cold, or the flu while you are taking this medicine, let your doctor know right away.
- An increased risk of blood or nervous system disorders. Call your doctor if you have symptoms of blood disorders (such as bruising or bleeding) or symptoms of nervous system problems (such as numbness, weakness, tingling, or vision problems).
- A possible increased risk of lymphoma (a type of blood cancer). It is not clear whether this increase is because of the drug or because people with this disease may already have a higher risk. There have been reports of a rare kind of lymphoma, occurring mostly in children and teens taking TNF antagonists, that often results in death.
- An increased risk of liver injuries. Call your doctor if your skin starts to look yellow, if you are very tired, or if you have a fever or dark brown urine.
In very few cases, natalizumab has caused a serious and life-threatening disease called PML. Natalizumab is tightly controlled because of this. If you take natalizumab, you will need to enroll in a program called the Crohn's Disease–Tysabri Outreach Unified Commitment to Health (CD-TOUCH) Prescribing Program.
What To Think About
TNF antagonists are more expensive than other medicines used to treat Crohn's disease.
TNF antagonists are used for Crohn's disease and ulcerative colitis that has not improved (refractory disease) when treated with corticosteroids, aminosalicylates, antibiotics, azathioprine, or 6-mercaptopurine.
The use of TNF antagonists during pregnancy is still being studied. Some of them may be used when other medicines have not worked and the health of the mother or of the fetus (or both) is at risk. It is not known if TNF antagonists can pass from the mother to the baby in breast milk. If you have inflammatory bowel disease and you are pregnant, thinking about becoming pregnant, or breast-feeding, talk to your doctor about what medicines are safe for you to use.
Because adalimumab and certolizumab are given as a shot under the skin, you may be able to do the shots yourself after your doctor has shown you how.
- Friedman S, Lichtenstein GR (2006). Crohn's disease. In MM Wolfe et al., eds., Therapy of Digestive Disorders, 2nd ed., pp. 785–801. Philadelphia: Saunders Elsevier.
- American Gastroenterological Association (2007). American Gastroenterological Association consensus development conference on the use of biologics in the treatment of inflammatory bowel disease. Gastroenterology, 133(1): 312–339.
- Schreiber S, et al. (2007). Maintenance therapy with certolizumab pegol for Crohn's disease. New England Journal of Medicine, 357(3): 239–250.
- Sandborn WJ, et al. (2007). Certolizumab pegol for the treatment of Crohn's disease. New England Journal of Medicine, 357(3): 228–238.
- MacDonald JK, McDonald JWD (2006). Natalizumab for induction of remission in Crohn's disease. Cochrane Database of Systematic Reviews (1). Oxford: Update Software.
- Rutgeerts P, et al. (2005). Infliximab for induction and maintenance therapy for ulcerative colitis. New England Journal of Medicine, 353(23): 2462–2476.
Last Updated: October 9, 2008
Author: Monica Rhodes