Jay W. Marks, MD, is a board-certified internist and gastroenterologist. He graduated from Yale University School of Medicine and trained in internal medicine and gastroenterology at UCLA/Cedars-Sinai Medical Center in Los Angeles.
Infliximab (Remicade) is an antibody that attaches to a protein called tumor necrosis factor-alpha (TNF-alpha). TNF-alpha is one of the proteins produced by immune cells during activation of the immune system. TNF-alpha, in turn, stimulates other cells of the immune system to produce and release other proteins that promote inflammation. In Crohn's disease, there is continued production of TNF-alpha as part of the immune activation. Infliximab, by attaching to TNF-alpha, blocks its activity and in so doing decreases the inflammation.
Infliximab, an antibody to TNF-alpha, is produced by the immune system of mice after the mice are injected with human TNF-alpha. The mouse antibody then is modified to make it look more like a human antibody, and this modified antibody is infliximab. Such modifications are necessary to decrease the likelihood of allergic reactions when the antibody is administered to humans. Infliximab is given by intravenous infusion over two hours. Patients are monitored throughout the infusion for adverse reactions.
In August 1998 the United States Food and Drug Administration approved the use of infliximab for the short-term treatment of moderate to severe Crohn's disease patients who respond inadequately to corticosteroids, azathioprine, or 6-MP.
Effectiveness of infliximab (Remicade)
Infliximab (Remicade) is an effective and fast-acting drug for the treatment of active Crohn's disease. In a study involving patients with moderate to severe Crohn's disease who were not responding to corticosteroids or
oral immuno-modulators, 65% experienced improvement in their disease after one infusion of infliximab. Some patients noticed improvement in symptoms within days of the infusion. Most patients experienced improvement within two weeks.
In patients who respond to infliximab, the improvements in symptoms can be dramatic. Moreover, there can be impressively rapid healing of the ulcers and the inflammation in the intestines after just one infusion.
The anal fistulae of Crohn's disease are troublesome and often difficult to treat. Infliximab has been found to be effective for treating fistulae.
Duration of benefits with infliximab (Remicade)
The majority of the patients who responded to a first infusion of infliximab developed recurrence of their disease within three months. However, studies have shown that repeated infusions of
infliximab every 8 weeks are safe and effective in maintaining remission in many patients over a
1 to 2 year period. Response to infliximab after repeated infusions sometimes is lost if the patient starts to develop antibodies to the infliximab (which attach to the infliximab and prevent it from working). Studies are now being done to determine the long-term safety and effectiveness of repeated infusions of infliximab.
One potential use of infliximab is to quickly control active and severe disease. The use of infliximab then may be followed by maintenance treatment with azathioprine, 6-MP or 5-ASA compounds. Azathioprine or 6-MP also may be helpful in preventing the development of antibodies against infliximab.
Side effects of infliximab (Remicade)
Infliximab generally is well-tolerated. There have been rare reports of side effects during infusions, including
chest pain,
shortness of breath, and nausea. These effects usually resolve spontaneously within minutes if the infusion is stopped. Other commonly-reported side effects include headache and
upper respiratory tract infection.
TNF-alpha is an important protein for defending the body against infections. Infliximab, like immuno-modulators, increases the risk for infection. One case of salmonella colitis and several cases of pneumonia have been reported with the use of infliximab. There also have been cases of tuberculosis (TB) reported after the use of infliximab.
More recently, a rare form lymphoma called hepatosplenic T-cell lymphoma has been described associated with azathioprine therapy for Crohn's disease either alone or in combination with infliximab. Although there is not much known about this disease, it appears to be aggressive and poorly responsive to treatment.
Because infliximab is partly a mouse protein, it may induce an immune reaction
when given to humans, especially with repeated infusions. In addition to the
side effects that occur while the infusion is being given, patients also may
develop a "delayed allergic reaction" that occurs 7 to 10 days after receiving the
infliximab. This type of reaction may cause flu-like symptoms with fever, joint
pain and swelling, and a worsening of Crohn's disease symptoms. It can be
serious, and if it occurs, a physician should be contacted. Paradoxically, those
patients who have more frequent infusions of infliximab are less likely to
develop this type of delayed reaction compared to those patients who receive
infusions separated by long intervals (6-12 months).
Infliximab is typically given to induce remission in a three dose cycle at time zero, 2 weeks, then 4 weeks after that. After remission is attained, maintenance dosing can be given every other month.
Rare cases of nerve inflammation such as
optic neuritis (inflammation of the nerve of the eye) and
motor neuropathy
also has reported with the use of infliximab.
Precautions with infliximab(Remicade)
Infliximab can aggravate and cause the spread of an existing infection. Therefore, it should not be given to patients with pneumonia, urinary tract infections, or abscess (localized collection of pus).
It now is recommended that patients be
tested for TB prior to receiving infliximab. Patients who previously had TB should inform their physician of this before they receive infliximab.
Infliximab also can cause the spread of cancer cells; therefore, it should not be given to patients with cancer.
Infliximab can promote intestinal scarring (part of the process of healing) and, therefore, can worsen strictures (narrowed areas of the intestine caused by inflammation and subsequent scaring) and lead to intestinal obstruction. It also can cause partial healing (partial closure) of anal fistulae. Partial closure of fistulae impedes drainage of fluid through the fistulae, and may result in collections of fluid in which bacteria multiply, which can result in abscesses.
The effects infliximab on the fetus are not known, although the literature suggests that this medication is safe for women to continue until week 32 of pregnancy. At that time, the risk of exposure of the fetus to this medication via placental transfer is increased. Infliximab is listed as a pregnancy category B drug by the FDA (meaning that animal studies show no increased risk, but there are no human studies).
Because infliximab is partly a mouse protein, some patients can develop antibodies against infliximab with repeated infusions. Such antibodies can decrease the effectiveness of the drug. The chance of developing such antibodies can be decreased by the concomitant use of 6-MP and corticosteroids. There are ongoing studies in patients who have lost their initial response to infliximab to determine whether measurement of anti-infliximab antibodies will be helpful in guiding further treatment. Results of these studies are not yet available. There are some reports of worsening
heart disease in patients who have received
infliximab (Remicade). The precise mechanism and role of infliximab in the development of this side effect is unclear. As a precaution, individuals with heart disease should inform their physician of this condition before receiving infliximab.
While infliximab represents an exciting new class of medications in the fight against Crohn's disease, caution is warranted in its use. The long-term safety and effectiveness is not yet known although recent 10 year data from patients who received at least 1 dose of infliximab for CD showed the safety profile similar to what was previously known. In that data set, the treated patients seemed to have an increased risk of developing infections, infusion reactions, autoimmune reactions, and malignancy5.
Crohn's Disease - Symptoms at Onset of DiseaseQuestion: The symptoms of crohn's disease can vary greatly from patient to patient. What were your symptoms at the onset of your disease?
Abdominal pain is pain in the belly and can be acute or chronic. Causes include inflammation, distention of an organ, and loss of the blood supply to an organ. Abdominal pain can reflect a major problem with one of the organs in the abdomen such as the appendix, gallbladder, large and small intestine, pancreas, liver, colon, duodenum, and spleen.
Diarrhea is a change is the frequency and looseness of bowel movements. Cramping, abdominal pain, and the sensation of rectal urgency are all symptoms of diarrhea. Absorbents and anti-motility medications are used to treat diarrhea.
Gallstones are stones that form when substances in the bile harden. Gallstones (formed in the gallbladder) can be as small as a grain of sand or as large as a golf ball. There can be just one large stone, hundreds of tiny stones, or any combination. The majority of gallstones do not cause symptoms.
Pink eye, also called conjunctivitis, is redness or irritation of the conjunctivae, the membranes on the inner part of the eyelids and the membranes covering the whites of the eyes. These membranes react to a wide range of bacteria, viruses, allergy-provoking agents, irritants, and toxic agents.
Anemia is the condition of having less than the normal number of red blood cells or less than the normal quantity of hemoglobin in the blood. The oxygen-carrying capacity of the blood is, therefore, decreased.
Colon cancer is a malignancy that arises from the inner lining of the colon. Most, if not all, of these cancers develop from colonic polyps. Removal of these precancerous polyps can prevent colon cancer.
Anal itching is the irritation of the skin at the exit of the rectum, known as the anus, accompanied by the desire to scratch. Causes include everything from irritating foods we eat, to certain disease and infections. Treatment options include local anesthetics, vasoconstrictors, protectants, astringents, antiseptics, keratolytics, analgesics, and corticosteroids. If condition persists, a doctor examination may be needed to identify an underlying cause.
Clostridium difficile (C. difficile) is a bacterium, and is one of the most common causes of infection of the colon. C. difficile spores are found frequently in hospitals, nursing homes, extended care facilities, and nurseries for newborn infants. They can be found on bedpans, furniture, toilet seats, linens, telephones, stethoscopes, fingernails, rings, floors, infants' rooms, and diaper pails. They even can be carried by pets. Antibiotic-associated (C. difficile) colitis is an infection of the colon caused by C. difficile that occurs primarily among individuals who have been using antibiotics. Treatment for C. difficile colitis hydration, replenishment of electrolyte deficiencies, discontinuing the antibiotic that caused the colitis, and using antibiotics to eradicate the C. difficile bacterium.
Ulcerative colitis is a chronic inflammation of the colon. Symptoms include abdominal pain, diarrhea, and rectal bleeding. Ulcerative colitis is closely related to Crohn's disease, and together they are referred to as inflammatory bowel disease. Treatment depends upon the type of ulcerative colitis diagnosed.
Small intestinal bacterial overgrowth (SIBO) refers to a condition in which abnormally large numbers of bacteria (at least 100,000 bacteria per ml of fluid) are present in the small intestine and the types of bacteria in the small intestine resemble more the bacteria of the colon than the small intestine. There are many conditions associated with small intestinal bacterial overgrowth, to include: diabetes, scleroderma, Crohn's disease, and others. There is a striking similarity between the symptoms of irritable bowel syndrome and SIBO. It has been theorized that SIBO may be responsible for the symptoms of at least some patients with irritable bowel syndrome. Symptoms of SIBO include: excess gas, abdominal bloating, diarrhea, and abdominal pain.
Ankylosing spondylitis is a type of arthritis that causes chronic inflammation of the spine. The tendency to develop ankylosing spondylitis is genetically inherited.
Psoriatic arthritis is a disease that causes skin and joint inflammation. Symptoms include painful, stiff, and swollen joints, tendinitis, and organ inflammation. Treatment involves antiinflammatory medications and exercise.
Inflammation of the inner lining of the colon is referred to as colitis. Symptoms of the inflammation of the colon lining include diarrhea, pain, and blood in the stool. There are several causes of colitis including infection, ischemia of the colon, inflammatory bowel disease (Crohn's disease, Ulcerative colitis, or microscopic colitis). Treatment depends on the cause of the colitis.
Canker sore is a small ulcer crater in the lining of the mouth. Canker sores are one of the most
common problems that occur in the mouth. Canker sores typically last for
10-14 days and they heal without leaving a scar.
The inflammatory bowel diseases (IBD) are Crohn's disease (CD) and ulcerative colitis (UC). The intestinal complications of Crohn's disease and ulcerative colitis differ because of the characteristically dissimilar behaviors of the intestinal inflammation in these two diseases.
Gastritis is an inflammation of the stomach lining. Causes of gastritis include drinking too much alcohol, medications such as NSAIDs, ibuprofen, aspirin, H. pylori infection, severe infections, burns, anemia, and autoimmune disorders. Gastritis is diagnosed with endoscopy, blood tests, or stool tests. Treatment depends upon the cause of gastritis.
Erythema nodosum is a skin inflammation that results in reddish, painful, tender lumps most commonly located in the front of the legs below the knees. Erythema nodosum can resolve on its own in 3 to 6 weeks, leaving a bruised area. Treatments include anti-inflammatory medications and cortisone by mouth or injection.
Corticosteroid drugs such as prednisone and prednisolone are commonly used to treat asthma, allergic reactions, RA, and IBD. Steroids such as these do have serious drawbacks such as steroid withdrawal symptoms such as: fatigue, weakness, decreased appetite, weight loss, nausea, vomiting, abdominal pain, and diarrhea. Speak with your healthcare provider prior to tapering off steroid medications.
Chronic pain is pain (an unpleasant sense of discomfort) that persists or progresses over a long period of time. In contrast to acute pain that arises suddenly in response to a specific injury and is usually treatable, chronic pain persists over time and is often resistant to medical treatments.
Bronchiectasis is a condition in which the bronchial tubes of the lung become damaged. Inflammation from infection or other causes destroys the smooth muscles of the bronchial tubes. Bronchiectasis is a form of COPD (which includes emphysema and chronic bronchitis). There are three primary types of bronchiectasis: 1) cylindrical bronchiectasis; 2) saccular bronchiectasis; and 3) cystic bronchiectasis. Bronchiectasis may also be acquired or congenital. The most common symptoms of bronchiectasis are recurrent cough and sputum production. There is no cure for bronchiectasis. Treatment is often geared toward controlling the symptoms of bronchiectasis.
Primary sclerosing cholangitis (PSC) is a chronic, progressive disease of the bile ducts that channel bile from the liver into the intestines. There is an association between primary sclerosing cholangitis and ulcerative colitis and Crohn's disease. Symptoms of primary sclerosing cholangitis include abnormal liver blood tests, itching, fatigue, and jaundice. Primary sclerosing cholangitis is treated with medications and in some cases, liver transplant.
Digestion is the complex process of turning food you eat into the energy you need to survive. The digestive process also involves creating waste to be eliminated, and is made of a series of muscles that coordinate the movement of food.
Vitamin D deficiency has been linked with rickets, cancer, cardiovascular disease, severe asthma in children and cognitive impairment in older adults. Causes include not ingesting enough of the vitamin over time, having limited exposure to sunlight, having dark skin, and obesity. Symptoms include bone pain and muscle weakness. Treatment for vitamin D deficiency involves obtaining more vitamin D through supplements, diet, or exposure to sunlight.
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