Types of Medications for Crohn's Disease

There is no cure for Crohn's disease, a chronic inflammatory disease that causes ulcerations of the small and large intestines (colon). Medications for Crohn's disease are aimed at putting it into remission, maintaining remission, minimizing side effects of treatment, and improving the person's quality of life.

There is no cure for Crohn's disease, a chronic inflammatory disease that causes ulcerations of the small and large intestines (colon). The symptoms of abdominal pain, diarrhea, rectal bleeding, and weight loss caused by Crohn's can come and go, which are typically managed with medications and treatments.

Medications for Crohn's disease are aimed at putting it into remission, maintaining remission, minimizing side effects of treatment, and improving the person's quality of life.

While surgery can significantly improve the quality of life for some, the disease often recurs after surgery.

As researchers continue to investigate the role of genetics and environmental factors in Crohn's disease, we may see better treatment options and maybe even one day be able to prevent the 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).

• 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, most patients with Crohn's disease involving both the ileum (distal small intestine) and colon, must take 5-ASA 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 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.

• Rowasa is 5-ASA in enema form and is used in treating Crohn's disease in which there is inflammation in and near the rectum. The enema usually is administered at bedtime, and patients are encouraged to retain the enema through the night. The enema contains sulfite and should not be used by patients with sulfite allergy. Otherwise, Rowasa enemas are safe and well tolerated.
• Both enemas and suppositories have been shown to be effective in maintaining remission in patients with ulcerative colitis limited to the distal colon and rectum.

• 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 corticosteroids

The 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.

Children receiving corticosteroids experience stunted growth.

Long-term use of high doses of corticosteroids usually produces predictable and potentially serious side effects for example, stunted growth in children, aseptic necrosis of the hip joints, and osteoporosis.

Budesonide (Entocort EC)

• Budesonide (Entocort EC) is another form of corticosteroid used for treating Crohn's disease. Like the systemic corticosteroids, budesonide is a potent anti-inflammatory medication. Unlike systemic corticosteroids, budesonide acts only via direct contact with the inflamed tissues (topically) and not systemically.
• Budesonide capsules contain granules that allow a slow release of the drug into the ileum and the colon. In a double-blind multicenter study (published in 1998), 182 patients with Crohn's ileitis and/or Crohn's disease of the right colon were treated with either budesonide (9 mg daily) or Pentasa (2 grams twice daily). Budesonide was more effective than Pentasa in inducing remissions while the side effects were similar to Pentasa. In another study comparing the effectiveness of budesonide with corticosteroids, budesonide was not better than systemic corticosteroids in treating Crohn's disease but had fewer side effects.
• Because budesonide is broken down by the liver into inactive chemicals, it has fewer side effects than systemic corticosteroids. It also suppresses the adrenal glands less than systemic corticosteroids. Budesonide also is available as an enema for the treatment of proctitis.
• Budesonide has not been shown to be effective in maintaining remission in patients with Crohn's disease. If used long-term, budesonide also may cause some of the same side effects as corticosteroids. Because of this, the use of budesonide should be limited to short-term treatment for inducing remission. As most budesonide is released in the terminal ileum, it will have its best results in Crohn's disease limited to the terminal ileum.

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.

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).

• Azathioprine is converted into 6-MP in the body and 6-MP then is partially converted in the body into inactive and non-marrow toxic chemicals by an enzyme called thiopurine methyltransferase (TPMT). These chemicals then are eliminated from the body.
• The activity of TPMT enzyme (the ability of the enzyme to convert 6-MP into inactive and non-marrow toxic chemicals) is genetically determined, and approximately 10% of the population in the Untied States has a reduced or absent TPMT activity. In this 10% of patients, 6-MP accumulates and is converted into chemicals that are toxic to the bone marrow where blood cells are produced. Thus, when given normal doses of azathioprine or 6-MP, these patients with reduced or absent TPMT activities can develop seriously low white blood cell counts for prolonged periods of time, exposing them to serious life-threatening infections.
• The U.S. Food and Drug Administration recommends doctors check TPMT levels prior to starting treatment with azathioprine or 6-MP. Patients found to have genes associated with reduced or absent TPMT activity are treated with alternative medications or are prescribed substantially lower than normal doses of 6-MP or azathioprine.
• Having normal TPMT genes is no guarantee against azathioprine or 6-MP toxicity. Rarely, a patient with normal TPMT genes can develop severe toxicity in the bone marrow and a low white blood cell count even with normal doses of 6-MP or azathioprine. Also, hepatotoxicity in the presence of normal TPMT levels has been reported. All patients taking 6-MP or azathioprine (regardless of TPMT genetics) have to be closely monitored by periodic blood counts and liver enzyme tests for as long as the medication is taken.
• Allopurinol (Zyloprim), used in treating high blood uric acids levels, can induce bone marrow toxicity when used together with azathioprine or 6-MP. Allopurinol (Zyloprim) used together with azathioprine or 6-MP has similar effect as having reduced TPMT activity, causing increased accumulation of the 6-MP metabolite that is toxic to the bone marrow.

In addition to monitoring blood cell counts and liver tests, doctors also may measure blood levels of the chemicals that are formed from 6-MP (6-MP metabolites), which can be helpful in several situations such as if a patient's disease:

• 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.

Patients have been maintained on 6-MP or azathioprine for years without significant long-term side effects. Patients on long-term azathioprine or 6-MP, however, should be closely monitored by their doctors.

There are data suggesting that patients on long-term maintenance fare better than those who stop these medications. Thus, those who stop azathioprine or 6-MP are more likely to experience recurrence of their disease and are more likely to need corticosteroids or undergo surgery.

Azathioprine (Imuran, Azasan) and 6-mercaptopurine (6-MP, Purinethol) are medications that weaken the body's immune system by reducing the population of a class of immune cells called lymphocytes.

Azathioprine and 6-MP are related chemically. In high doses, these two drugs have been useful in preventing rejection of transplanted organs and in treating leukemia. In low doses, they have been used for many years to treat patients with moderate to severe Crohn's disease and ulcerative colitis.

Azathioprine and 6-MP are increasingly recognized as valuable drugs in treating Crohn's disease and ulcerative colitis. A majority of patients with moderate to severe disease will benefit from these drugs. Azathioprine and 6-MP are used primarily in the following situations:

• 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.

Side effects of azathioprine and 6-MP include increased vulnerability to infections, inflammation of the liver (hepatitis) and the pancreas (pancreatitis), and bone marrow toxicity (interference with the formation of cells that circulate in the blood).

One problem with 6-MP and azathioprine is their slow onset of action. Typically, full benefit of these drugs is not realized for three months or longer. During this time, corticosteroids frequently have to be maintained at high levels to control inflammation.

Studies have shown that giving higher doses of 6-MP early can hasten the benefit of 6-MP without increasing the toxicity in most patients, but some patients do develop severe bone marrow toxicity.

Scientists now believe that an individual's vulnerability to 6-MP toxicity is genetically inherited. Blood tests can be performed to identify those individuals with increased vulnerability to 6-MP toxicity. Blood tests also can be performed to measure the levels of certain by-products of 6-MP. The levels of these by-products in the blood help doctors to more quickly determine whether the dose of 6-MP is right for the patient.

• 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 have been 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 of 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.

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)

• 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 in 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)

• 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.

Vedolizumab (Entyvio)

• Vedolizumab (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 (Stelara)

• Ustekinumab (Stelara) 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.

• The drug 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.

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 induce and maintain 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 maintain fistula closure in adult patients with fistulizing disease.
• The signs and symptoms of Crohn’s disease in children and induce and maintain 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.

Common side effects

• The most common side effects of Renflexis 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

• Serious side effects of Renflexis 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 maintain fistula closure in adult patients with fistulizing disease.
  • Reduce the signs and symptoms of pediatric Crohn’s disease and induce and maintain 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.

Common side effects

• The most common side effects of Inflectra include respiratory infections, bronchitis, sinus infections and sore throat, runny or stuffy nose, headache, coughing, stomach/abdominal pain, nausea, diarrhea, indigestion, fatigue, pain, oral thrush, joint pain, and urinary tract infection (UTI).

Serious side effects

• Serious side effects of Inflectra include serious infections, heart failure, liver injury, blood problems, nervous system disorders, allergic reactions, Lupus-like syndrome, and psoriasis.

Infusion reactions

• Infusion reactions can happen up to two hours after an infusion. Symptoms of infusion reactions may include fever, chills, chest pain, low blood pressure (hypotension) or high blood pressure (hypertension), shortness of breath, rash, and itching.