Diseases

Granulomatous Enteritis (Crohn's Disease) Information

5-ASA (mesalamine) oral medications for Crohn's disease

5-aminosalicylic acid (5-ASA), also called mesalamine, is similar chemically to aspirin. Aspirin is an anti-inflammatory drug that has been used for many years for treating arthritis, bursitis, and tendonitis (conditions of tissue inflammation). Aspirin is not effective in treating Crohn's disease and ulcerative colitis and may even worsen the inflammation. Studies suggest that aspirin might actually decrease future risk of developing colorectal cancer in the general population. On the other hand, 5-ASA can be effective in treating Crohn's disease and ulcerative colitis if the drug can be delivered topically onto the inflamed intestinal lining.

5-ASA oral and rectal medications for Crohn's disease

5-aminosalicylic acid (5-ASA), also called mesalamine, is similar chemically to aspirin. Aspirin is an anti-inflammatory drug that has been used for many years for treating arthritis, bursitis, and tendonitis (conditions of tissue inflammation). Aspirin, however, is not effective in treating Crohn's disease and ulcerative colitis and may even worsen the inflammation. Recent studies suggest that aspirin might actually decrease future risk of developing colorectal cancer in the general population.On the other hand, 5-ASA can be effective in treating Crohn's disease and ulcerative colitis if the drug can be delivered topically onto the inflamed intestinal lining. For example, mesalamine (Rowasa) is an enema containing 5-ASA that is effective in treating inflammation in the rectum. However, the enema solution cannot reach high enough to treat inflammation in the upper colon and the small intestine. Therefore, for most patients with Crohn's disease involving both the ileum (distal small intestine) and colon, 5-ASA must be taken orally.If pure 5-ASA is taken orally, however, most of the 5-ASA would be absorbed in the stomach and the upper small intestine, and very little 5-ASA would reach the ileum and colon. To be effective as an oral agent in treating Crohn's disease, 5-ASA has to be modified chemically to escape absorption by the stomach and the upper intestines.Sulfasalazine (Azulfidine)Sulfasalazine (Azulfidine) was the first modified 5-ASA compound used in the treatment of Crohn's colitis and ulcerative colitis. It has been used successfully for many years to induce remissions among patients with mild to moderate ulcerative colitis. Sulfasalazine also has been used for prolonged periods for maintaining remissions.Most of the side effects of sulfasalazine include nausea, heartburn, headache, anemia, skin rashes, and, in rare instances, hepatitis and kidney inflammation. In men, sulfasalazine can reduce the sperm count. The reduction in sperm count is reversible, and the count usually becomes normal after the sulfasalazine is discontinued or changed to a different 5- ASA compound.Some 5-ASA compounds, for example, mesalamine (Asacol and Pentasa), do not have the sulfapyridine component and have fewer side effects than sulfasalazine, and are used more frequently for treating Crohn's disease and ulcerative colitis.Mesalamine (Asacol)Asacol is effective in inducing remissions in patients with mild to moderate ulcerative colitis. It also is effective when used in the longer term to maintain remissions. Some studies have shown that Asacol also is effective in treating Crohn's ileitis and ileo-colitis, as well as in maintaining remission in patients with Crohn's disease.Mesalamine (Pentasa)Pentasa is a capsule consisting of small spheres containing 5-ASA. Pentasa is sulfa-free. As the capsule travels down the intestines, the 5-ASA inside the spheres is released slowly into the intestine. Unlike Asacol, the active drug 5-ASA in Pentasa is released into the small intestine as well as the colon. Pentasa can be effective in treating inflammation in the small intestine and is currently the most commonly used 5-ASA compound for treating mild to moderate Crohn's disease in the small intestine.Patients with Crohn's disease occasionally undergo surgery to relieve small intestinal obstruction, drain abscesses, or remove fistulae. Usually, the diseased portions of the intestines are removed during surgery. After successful surgery, patients can be free of disease and symptoms (in remission) for a while. In many patients, however, Crohn's disease eventually returns. Pentasa helps maintain remissions and reduces the chances of the recurrence of Crohn's disease after surgery.Olsalazine (Dipentum)Olsalazine (Dipentum) is a capsule filled with a drug in which two molecules of 5-ASA are joined together by a chemical bond. In this form, the 5-ASA cannot be absorbed from the stomach and intestine. Intestinal bacteria are able to break apart the two molecules releasing the active individual 5-ASA molecules into the intestine. Since intestinal bacteria are more abundant in the ileum and colon, most of the active 5-ASA is released in these areas. Therefore, olsalazine is most effective for disease that is limited to the ileum or colon. Although clinical studies have shown that olsalazine is effective for maintenance of remission in ulcerative colitis, some patients experience diarrhea when taking olsalazine. Because of this, olsalazine is not often used.Balsalazide (Colazal)Balsalazide (Colazal) is a capsule in which the 5-ASA is linked by a chemical bond to another molecule that is inert (without an effect on the intestine) and prevents the 5-ASA from being absorbed. This drug is able to travel through the intestine unchanged until it reaches the end of the small bowel (terminal ileum) and colon. There, intestinal bacteria split the 5-ASA and the inert molecule releasing the 5-ASA. Because intestinal bacteria are most abundant in the terminal ileum and colon, balsalazide is used to treat inflammation predominantly localized to the colon.Side effects of oral 5-ASA compounds

• The 5-ASA compounds have fewer side effects than Azulfidine and also do not reduce sperm counts. They are safe medications for long-term use and are well-tolerated.
• Patients allergic to aspirin should avoid 5-ASA compounds because they are similar chemically to aspirin.
• Rarely, kidney and lung inflammation has been reported with the use of 5-ASA compounds. 5-ASA should be used with caution in patients with kidney disease. It also is recommended that blood tests of kidney function be done before starting and periodically during treatment.
• Rare instances of worsening of diarrhea, cramps, and abdominal pain, at times accompanied by fever, rash, and malaise, may occur. This reaction is believed to represent an allergy to the 5-ASA compound.

Adalimumab (Humira), Certolizumab pegol (Cimzia), Natalizumab (Tysabri)

Humira (adalimumab)

• Humira (adalimumab) is used to treat adult patients with moderately to severely active Crohn's disease. Adalimumab (Humira) is an anti-TNF agent similar to infliximab and decreases inflammation by blocking tumor necrosis factor (TNF-alpha).
• Adalimumab generally is well-tolerated. The most common side effect is skin reactions at the site of injection with swelling, itching, or redness. Other common side effects include upper respiratory infections, sinusitis, and nausea.
• Serious side effects of Humira include infections, tuberculosis, lymphoma, nervous system inflammation, lupus symptoms, worsening heart disease such as heart failure, and rarely, Severe allergic reactions with rash, difficulty breathing, and severe low blood pressure or shock.

• Certolizumab pegol (Cimzia) is used for the treatment of moderate to severe Crohn's disease in patients who do not respond sufficiently or adequately to standard medical therapy.
• Certolizumab is generally well-tolerated. Common side effects of Cimzia include runny or stuffy nose, injection site pain or other injection site reaction, upper respiratory tract infections, urinary tract infections, or a rash.
• Serious side effects of Cimzia include possible increase the risk for serious infections including tuberculosis, worsening of heart failure, , and
• hypersensitivity reactions, for example, angioedema, hives allergic dermatitis, dizziness, shortness of breath, hot flushes, low blood pressure, malaise, and fainting (syncope). Patients experiencing symptoms of severe allergic reactions should seek emergency care immediately.

• Natalizumab (Tysabri) is a humanized monoclonal antibody to alpha-4 integrin and is effective in treatment of patients with moderate to severe CD and evidence of inflammation who have not responded to aminosalicylates, antibiotics, corticosteroids, immunomodulators, or TNF inhibitors. Doctors who are registered through the CD TOUCH prescribing program may prescribe this medication to patients. Natalizumab has also been used for some forms of multiple sclerosis.
• The most common side effects reported include headache, fatigue, upper respiratory infections, and nausea. The most serious adverse events reported have been hypersensitivity, immunosuppression/infections and progressive multifocal leukoencephalopathy.

Anti-inflammatory medications for Crohn's disease

Anti-inflammatory medications that decrease intestinal inflammation are similar to arthritis medications that decrease joint inflammation. Examples of types of anti-inflammatory medications used in the treatment of Crohn's disease are:

• 5 aminosalicylic acid (5-ASA) compounds, for example, sulfasalazine (Azulfidine) and mesalamine (Pentasa, Asacol, Dipentum, Colazal, Rowasa enema, Canasa suppository).
• Corticosteroids that act systemically (without the need for direct contact with the inflamed tissue) to decrease inflammation throughout the body. Systemic corticosteroids have important and predictable side effects if used long-term.
• Topical corticosteroids, for example, budesonide (Entocort EC). This class of corticosteroids has fewer side effects than systemic corticosteroids, which are absorbed into the body.
• Antibiotics that decrease inflammation, for example, metronidazole (Flagyl) and ciprofloxacin (Cipro).

Antibiotics for Crohn's disease

Antibiotics such as metronidazole (Flagyl) and ciprofloxacin (Cipro) have been used for treating Crohn's colitis. Flagyl also has been useful in treating anal fistulae in patients with Crohn's disease. The mechanism of action of these antibiotics in Crohn's disease is not well understood.Metronidazole (Flagyl)Metronidazole (Flagyl) is an antibiotic that is used for treating several infections caused by parasites (for example, giardia) and bacteria (for example, infections caused by anaerobic bacteria, and vaginal infections). It might have some activity in the treatment of Crohn's colitis and is particularly useful in treating patients with anal fistulae. Chronic use of metronidazole in doses higher than 1 gram daily can be associated with permanent nerve damage (peripheral neuropathy). The early symptoms of peripheral neuropathy are numbness and tingling in the fingertips, toes, and other parts of the extremities. Metronidazole should be stopped promptly if these symptoms appear. Metronidazole and alcohol together can cause severe nausea, vomiting, cramps, flushing, and headache. Patients taking metronidazole should avoid alcohol. Other side effects of metronidazole include nausea, headaches, loss of appetite, a metallic taste, and, rarely, a rash.Ciprofloxacin (Cipro)Ciprofloxacin (Cipro) is another antibiotic used in the treatment of Crohn's disease. It can be used in combination with metronidazole.

Biosimilar medications for Crohn's disease

A biosimilar medication is a drug product that is made to be similar to another already-approved drug. It is tested to be the same as its reference drug in terms of clinical uses, effectiveness, and product safety. A biosimilar medication must meet specific strict standards to be approved by the FDA. A biosimilar is not a generic form of a drug. A generic drug contains the same compounds as the original drug, while a biosimilar drug is highly similar to the reference drug, but not identical. Examples of biosimilars are Infliximab-abda (Renflexis) and Infliximab-dyyb (Inflectra).Infliximab-abda (Renflexis)Infliximab-abda (Renflexis) is biosimilar to infliximab (Remicade). Renflexis is a tumor necrosis factor (TNF) blocker used to reduce:Signs and symptoms of Crohn’s disease and inducing and maintaining clinical remission in adult patients with moderately to severely active disease who have had an inadequate response to conventional therapy.The number of draining enterocutaneous and recto-vaginal fistulas and maintains fistula closure in adult patients with fistulizing disease.The signs and symptoms of Crohn’s disease in children and inducing and maintaining clinical remission in pediatric patients with moderately to severely active disease who have had an inadequate response to conventional therapy.Renfexis is also used to treat ulcerative colitis, rheumatoid arthritis (in combination with methotrexate), ankylosing spondylitis, psoriatic arthritis, and plaque psoriasis.The most common side effects of Renflex is include infections (upper respiratory infection, sinus infection, throat infection, bronchitis, urinary tract infection), infusion-related reactions, headache, abdominal pain, fever or chills, cardiopulmonary reactions (chest pain, high or low blood pressure, shortness of breath), itching, hives, nausea, diarrhea, indigestion, cough, rash, fatigue, yeast infection, and joint pain.Serious side effects of Renflex is include serious infections, heart failure, liver injury, blood problems, nervous system disorders, allergic reactions, Lupus-like syndrome, and psoriasis.Infliximab-dyyb (Inflectra)Infliximab-dyyb (Inflectra) is biosimilar to infliximab (Remicade). Inflectra is a tumor necrosis factor (TNF) blocker used for reducing signs and symptoms of Crohn’s disease and inducing and maintaining clinical remission in adult patients with moderately to severely active disease who have had an inadequate response to conventional therapy.Inflectra also is used to:

• Reduce the number of draining enterocutaneous and recto-vaginal fistulas and maintaining fistula closure in adult patients with fistulizing disease.
• Reduce the signs and symptoms of pediatric Crohn’s disease and inducing and maintaining clinical remission in pediatric patients with moderately to severely active disease who have had an inadequate response to conventional therapy.
• Treat ulcerative colitis, rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and plaque psoriasis.

Chron's disease treatment medications

There is no medication that can cure Crohn's disease. Patients with Crohn's disease typically will experience flares, or periods of relapse (worsening of inflammation) followed by periods of remission (lessening of inflammation) lasting months to years. During relapses, symptoms of abdominal pain, diarrhea, and rectal bleeding worsen. During remissions, these symptoms improve. Remissions usually occur because of treatment with medications or surgery, but occasionally they occur spontaneously without any treatment.Since there is no cure for Crohn's disease, the goals of treatment are to 1) induce remissions, 2) maintain remissions, 3) minimize the side effects of treatment, and 4) improve the quality of life. Treatment of Crohn's disease and ulcerative colitis with medications is similar though not always identical.Anti-inflammatory agents such as 5-ASA compounds and corticosteroids, topical antibiotics, immunomodulators, and biosimilars are medications used to treat Crohn’s disease.Selection of treatment regimens depends on disease severity, disease location, and disease-associated complications. Various guidelines recommend that approaches be sequential - initially to induce clinical remission, and then to maintain remissions. Initial evidence of improvement should be seen within 2 to 4 weeks and maximal improvement should be seen in 12 to 16 weeks. The classic approach to therapy in Crohn's disease has been a "step-up" approach starting with the least toxic agents for mild disease, and increasingly more aggressive treatment for more severe disease, or patients who have not responded to less toxic agents. Treatment has been moving toward a "top-down" approach (early aggressive management) which might decrease exposure to anti-inflammatory agents and increase exposure to agents that enhance mucosal healing that might prevent future complications.

Corticosteroids for Crohn's disease

Corticosteroids (for example, prednisone, prednisolone, hydrocortisone, etc.) have been used for many years to treat patients with moderate to severe Crohn's disease and ulcerative colitis and to treat patients who fail to respond to 5-ASA. Unlike 5-ASA, corticosteroids do not require direct contact with the inflamed intestinal tissues to be effective.Oral corticosteroids are potent anti-inflammatory medications. After absorption, corticosteroids exert prompt anti-inflammatory actions throughout the body, including the intestines. Consequently, they are used in treating Crohn's disease anywhere in the small intestine, as well as ulcerative and Crohn's colitis. In critically ill patients, intravenous corticosteroids (such as hydrocortisone) can be given in the hospital. For patients with proctitis, hydrocortisone enemas (Cortenema) can be used to deliver the corticosteroid directly to the inflamed tissue. By using the corticosteroid topically, less of it is absorbed into the body and the frequency and severity of side effects are lessened (but not eliminated) as compared with systemic corticosteroids.Corticosteroids are faster-acting than 5-ASA, and patients frequently experience improvement in their symptoms within days of beginning them. Corticosteroids, however, do not appear to be useful in maintaining remission in Crohn's disease and ulcerative colitis or in preventing the return of Crohn's disease after surgery.Side effects of corticosteroidsThe frequency and severity of side effects of corticosteroids depend on the dose and duration of their use. Short courses of corticosteroids usually are well tolerated with few and mild side effects. Examples of side effects of short-course corticosteroids include

• rounding of the face (moon face),
• acne,
• increased body hair,
• diabetes,
• weight gain,
• high blood pressure,
• cataracts,
• glaucoma,
• increased susceptibility to infections,
• muscle weakness,
• depression,
• insomnia,
• mood swings,
• personality changes,
• irritability, and
• thinning of the bones (osteoporosis) with fractures of the spine.

Crohn's disease definition and facts

• Crohn's disease is a chronic inflammatory disease of the gastrointestinal (digestive, GI) tract.
• Symptoms of Crohn’s disease include:
  • Abdominal pain
  • Diarrhea
  • Vomiting
  • Fever
  • Bloody diarrhea
  • Anal fistulae
  • Perirectal abscesses
  • Weight loss
• The cause of Crohn's disease is unknown.
• Crohn’s disease is not contagious. You cannot “get” it from another person.
• Diet can affect and trigger Crohn’s disease flare-ups; however, it is doubtful that diet causes the disease.
• Researchers and doctors do not know the cause of Crohn’s disease; however, some suspect that the cause is due to certain bacteria, for example, mycobacterium.
• Crohn's disease can cause ulcers in the small intestine, colon, or both. The disease also may cause obstruction of the small intestine.
• Associated sign and symptoms of Crohn's disease include reddish, tender skin nodules, and inflammation of the joints, spine, eyes, and liver.
• Crohn’s disease and ulcerative colitis (another chronic inflammatory condition of the colon) are a type of inflammatory bowel disease (IBD).
• The diagnosis of Crohn's disease is made by barium enema, barium X-ray of the small bowel, and colonoscopy.
• The choice of treatment for Crohn's disease depends on the location and severity of the disease.
• Treatment of Crohn's disease includes 5-ASA compounds and corticosteroids, topical antibiotics, immunomodulators, and biosimilars drugs for suppressing inflammation or the immune system; antibiotics, and surgery.
• Complications of Crohn’s disease include megacolon and rupture of the intestine, painful eye conditions, arthritis, inflammation of the low back and spine, hepatitis, cirrhosis, jaundice, and cancer.
• Inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) are two different problems with the digestive tract (gastrointestinal, GI).

Immuno-modulator medications

Immuno-modulator drugs decrease tissue inflammation by reducing the population of immune cells and/or by interfering with their production of proteins. Decreasing the activity of the immune system with immuno-modulators increases the risk of infections; however, the benefits of controlling moderate to severe Crohn's disease usually outweigh the risks of infection due to weakened immunity. Examples of immuno-modulators are:

• 6-mercaptopurine (6-MP),
• azathioprine (Imuran),
• methotrexate (Rheumatrex, Trexall, MTX, Mexate),
• infliximab (Remicade),
• adalimumab (Humira),
• certolizumab (Cimzia), and
• natalizumab (Tysabri).

• Severe Crohn's disease and ulcerative colitis not responding to corticosteroids.
• The presence of undesirable corticosteroid-related side effects.
• Corticosteroid dependency, a condition in which patients are unable to discontinue corticosteroids without developing relapses of their disease.
• Maintenance of remission.

• is not responding to standard doses of 6-MP or azathioprine and his/her 6-MP blood metabolite levels are low, doctors may increase the 6-MP or azathioprine dose;
• is not responding to treatment and his/her 6-MP blood metabolite levels are zero, he/she is not taking his/her medication. The lack of response in this case is due to patient non-compliance.

Infliximab (Remicade)

Infliximab is approved for the short-term treatment of moderate to severe Crohn's disease patients who respond inadequately to corticosteroids, azathioprine, or 6-MP.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 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 immunomodulators, 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).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.Infliximab can aggravate and cause the spread of an existing infection. It should not be given to patients with pneumonia, urinary tract infections, or abscess (localized collection of pus). It 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 and it should not be given to patients with cancer.Infliximab can promote intestinal scarring (part of the process of healing) and 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 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 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.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 malignancy.

Surgery in Crohn's disease

There is no surgical cure for Crohn's disease. Even when all of the diseased parts of the intestines are removed, inflammation frequently recurs in previously healthy intestines months to years after the surgery. Surgery in Crohn's disease is used primarily for:

1. Removal of a diseased segment of the small intestine that is causing obstruction.
2. Drainage of pus from abdominal and peri-rectal abscesses.
3. Treatment of severe anal fistulae that do not respond to drugs.
4. Resection of internal fistulae (such as a fistula between the colon and bladder) that are causing infections.

• Commonly treated with oral mesalamine 3.2-4 g daily or sulfasalazine for ileocolonic or colonic disease as 3-6 g daily in divided doses (this approach has more recently been reported to be not very effective).
• Budesonide (9 mg/day) is effective for disease confined to ileum and/or right colon.
• Proton pump inhibitors might help with symptomatic improvement in patients with upper gastrointestinal Crohn's disease.

• Prednisone 40-60 mg/day until resolution of symptoms.
• Appropriate antibiotic therapy for infection or abscess.
• Azathioprine and 6-MP are effective for maintaining a steroid-induced remission.
• Methotrexate 25 mg/wk is effective for steroid-dependent and steroid-refractory Crohn's disease.
• Infliximab, adalimumab, and certolizumab pegol are effective in the treatment of moderate to severely active disease in patients who have not responded to adequate therapy with a steroid or immunosuppressive agent.
• Natalizumab is effective in the treatment of patients with moderate to severely active CD who have had an inadequate response or are unable to tolerate conventional Crohn's disease therapy and anti-TNF antibody therapy.

• Surgical drainage for abscess
• Otherwise, treated medically with antibiotics (metronidazole), immunosuppressives, or infliximab.

Vedolijumab (Entyvio), Ustekinumab (Stelera), Methotrexate (Rheumatrex,Trexall)

Vedolijumab (Entyvio)Vedolijumab (Entyvio) is a type of monoclonal antibody called an integrin receptor antagonist indicated for adults with moderate to severe ulcerative colitis (UC) or moderate to severe Crohn's disease (CD) when certain other UC or CD medicines have not worked well enough or cannot be tolerated. Entyvio may help to reduce some symptoms, achieve remission, and reduce or stop the use of corticosteroids. Entyvio works to block the movement of certain gut directed white blood cells into the gastrointestinal (GI) tract, which helps control inflammation and may reduce the symptoms of UC and CD.The most common side effects of Entyvio include common cold symptoms (runny or stuffy nose, sinus pain, sneezing, cough), headache, joint pain, nausea, fever, infections of the nose and throat, tiredness, fatigue, upper respiratory tract infection, bronchitis, flu symptoms, back pain, rash, itching, sinus infection, sore throat, and pain in your arms or legs.Serious side effects of Entyvio include infusion reactions, serious allergic reactions, infections, progressive multifocal leukoencephalopathy (PML), and liver problems.Ustekinumab (Stelera)Ustekinumab (Stelera) is a human interleukin-12 and -23 antagonist indicated for the treatment of adult patients with moderately to severely active Crohn’s disease (CD) who have failed or were intolerant to treatment with immunomodulators or corticosteroids, but never failed a tumor necrosis factor (TNF) blocker; or failed or were intolerant to treatment with one or more TNF blockers. Stelara is also used to treat plaque psoriasis and psoriatic arthritis.The most common side effects of Stelara include injection site reactions (bruising, itching, pain, redness, swelling, and hardening of the skin), cold symptoms (stuffy nose, sneezing, sore throat), headache, tired feeling, diarrhea, or skin rash or itching.Serious side effects of Stelara include serious allergic reactions including feeling faint; swelling of your face, eyelids, tongue, or throat; chest tightness, or skin rash.Methotrexate (Rheumatrex, Trexall)Methotrexate (Rheumatrex, Trexall, MTX) is both an immunomodulator and anti-inflammatory medication. Methotrexate has been used for many years in the treatment of severe rheumatoid arthritis and psoriasis. It has been helpful in treating patients with moderate to severe Crohn's disease who are either not responding to azathioprine and 6-MP or are intolerant of them. Methotrexate also may be effective in patients with moderate to severe ulcerative colitis who are not responding to corticosteroids, azathioprine, or 6-MP.One major complication of methotrexate is the development of liver cirrhosis when the medication is given over a prolonged period of time (years). The risk of liver damage is higher in patients who also abuse alcohol or are severely obese. Other serious side effects of methotrexate include low white blood cell counts and inflammation of the lungs.Methotrexate should not be used in pregnant women because of toxic effects on the fetus.