Healthy Living

Immunosuppressive Drugs for Crohn's Disease

Immunosuppressive Drugs for Crohn's Disease

Key Takeaways

  • Crohn’s is a chronic disease.
  • There is no cure, but there are medications that help to mange the symptoms.
  • Immunosuppressants suppress the immune system and reduce the inflammation.

Crohn’s disease is an autoimmune disorder. Due to this disorder, the gastrointestinal tract is affected, and the lining of the digestive system is inflamed. Usually, it affects the colon, although it may affect any part. Ulcers, fistulas, or even cracks can develop in the intestine. This can block the passage of food and water and cause IBD. To treat this disorder, immunosuppressants are used, including azathiopurine, mercaptopurine, and methotrexate.

The side effects of these include headache, nausea, vomiting, and diarrhea. These immunosuppresant suppress the immune system and affect the ability of the body to fight infections. Some biological drugs used to treat moderate to severe Crohn’s or active Crohn’s disease are infliximab and adalimumbab. These medications are given by intravenous injection, and they reduce inflammation in specific areas and suppress the entire immune system.

Methotrexate

The growth of certain cells, such as cancer cells, skin cells, and bone marrow cells, is interrupted by methotrexate. Hence, certain types of breast cancer, cancer of head or lungs, and cancer of skin can be treated with methotrexate. Disorders such as rheumatoid arthritis and severe psoriasis can also be treated with methotrexate. Methotrexate is usually taken once or twice per week. It should not be taken daily. Some people who have taken this medicine daily have died by accident.

This medicine should not be used if the person has liver disease, bone marrow disorders, or blood cell disorders. The person should immediately contact the doctor if there is any unusual bruising or bleeding or any signs of infection. Due to methotrexate, the person may bleed or easily get infections, and the blood may clot, since methotrexate lowers the blood cells that fight infections. Serious side effects can be caused by the liver, lungs, or kidneys due to methotrexate. Other side effects include upper stomach pain, dark urine, loss of appetite, jaundice, dry cough, shortness of breath, clay colored stools, blood in the urine, and little to no urination. For patients with Crohn’s disease, methotrexate is recommended.

Methotrextae is usually recommended for those in whom other medications have been ineffective or who are unable to stop steroids without a flare of this disease. It may also help to improve Crohn’s fistulas. This drug is given once per week for people with Crohn’s disease, but it should be given as an injection for maximum efficacy. The injection can be given by the patient himself or by a family member. Patients who take methotrexate should also take a folic acid pill daily. Methotrexate is inexpensive. This drug should be used on an ongoing basis only if it is effective.

Some may experience side effects, such as nausea, fatigue, and headache. However, with lower doses, these issues can be resolved. Rarely, a person may experience other problems of the liver and lungs. During the course of treatment, the doctor should carefully monitor the patient by doing periodic blood tests. Methotrexate is known to cause birth defects; hence, it should not be used during pregnancy or by women who plan to become pregnant.

Infliximab

Infliximab is helpful and effective in treating ulcerative colitis, fistulas, and moderate to severe active Crohn’s disease. It is a biological therapy. As a long term therapy, it can be used to induce and maintain remission. It is given as a single dose through intravenous infusion. The patient is able to wait for months or even longer for the next dose. People with fistulas usually get three doses over a period of six weeks. It is better to wait for one or two weeks between two intravenous infusions to see the effectiveness of infliximab. Although some may respond within one or two weeks, infliximab blocks the TNF cells' action.

This reduces the inflammation. It also slows or stops the damage caused by the immune system by weakening it. Infliximab is a therapeutic agent for TNF-alfa, and it acts by binding and neutralizing TNF. High levels of TNF are found in the mucosa of Crohn’s disease patients. Thus, it is rendered biologically inactive. Infliximab became available in the market in the year 1999 for treatment of severe active or fistulizing Crohn’s disease. The recommended dose is 5 mg per kg of body weight. Currently, there are no guidelines about the number of administrations or the dosing interval between infusions. In cases of relapse, the repeated infusion may be needed every 14 weeks.

Side effects associated with infliximab are flushing, pain, swelling at the injection site, fever, chills, rash, and shortness of breath. If you experience side effects such as swelling of the ankles or feet, seizures, confusion, numbness, tingling of the arms or legs, joint or muscle pain, easy bruising or bleeding, changes in vision, weakness of muscles, numbness, chest pain, fast or slow irregular heart beat, butterfly shaped rash on the face, or pain/redness/swelling of the arms or legs, then inform your doctor.

If you experience any signs of infection, such as sore throat, trouble breathing, unusual vaginal discharge, night sweats, cough, painful or frequent urination, and oral thrush, then immediately inform your doctor. Rarely, this drug may cause liver disease. The symptoms of this include nausea, vomiting, loss of appetite, abdominal pain, yellowing of eyes or skin, and dark urine. Serious allergic reactions are rare.

Azathiopurine

Azathiopurine is used in the treatment of inflammatory bowel disease (IBD) such as Crohn’s disease. It is also used for ulcerative colitis. It has been in use since the 1960s and is commonly prescribed to patients with IBD. This drug belongs to a group of medications called thiopurines. These are immunosuppressants. They work to reduce the activity or weaken the immune system, since it attacks the digestive system and results in inflammation. Azathioprine works by reducing the number of white blood cells and thereby interrupts the activity of the immune system.

It is slow in its action; hence it needs to be taken at least 3 – 6 weeks in order to see its effects. Sometimes, people who have difficulty stopping corticosteroids are given this drug. It can also be combined with biological drugs, such as infliximab and adalimumab, and this is known as combination therapy. Due to high levels of enzymes, some people are not able to tolerate azathiopurine. Such people are given allopurinol, as well, which corrects the enzyme imbalance. Azathioprine comes in the form of a tablet. It is to be taken once daily with or without food. The dosage depends on height and weight of the patient, as well as the severity of IBD.

Before starting this medicine, the person will undergo some screening tests. This is to check the levels of the enzyme thiopurine methyl transferase. The person is more likely to experience the side effects associated with this drug if the levels of this enzyme are high. The person can be screened for immunity to some viruses and infections. The types of azithiopurine available are imuran, azapress, and azafalk. Reported side effects include nausea, vomiting, loss of appetite, inflammation of the pancreas, jaundice, liver problems, hair loss, allergic reactions, diarrhea or fatty stool, lung inflammation, increased risk of infections, increased risk of certain types of cancers, such as lymphomas, cancer of the vulva or cervix, and skin cancer.

Adalimumab

Sometimes it is known by the brand name ‘Humira.’ In children aged 6-17 years, adalimumab is used to treat severe active Crohn’s disease, and in adults, it is used to treat moderate to severe active Crohn’s disease. This drug can be considered as a suitable treatment if other drugs have not been effective or caused major side effects or if surgery is not the correct option for you. This drug is also used to treat ulcerative colitis in adults. It is a biological drug or a human monoclonal antibody against TNF-alpha.

Its molecular weight is approximately 148 kg and consists of 1330 amino acids. It belongs to a group of medicines called ‘anti-TNF’ drugs or therapies. It targets a protein called TNF-alpha, which is naturally produced as an immune response to fight infections caused by the inflammation in affected areas. Overproduction of this TNF-alpha is thought to be responsible for inflammation of the digestive system in people with IBD. The drug works by binding to TNF-alpha. It relieves the symptoms by reducing the inflammation.

It may take a few days to a few months for the drug to work. This drug is given as a subcutaneous injection. Since the digestive system can destroy this drug, it cannot be taken orally. The treatment of this drug is supervised by the doctor. The first injection can be given by the doctor. Thereafter, you may be able to self inject after taking proper training in injection techniques. Even a family member or a friend can be trained to give the injections.  

The dose prescribed may vary. Children are given smaller doses. The induction dose for an adult is 160 mg followed by an 80 mg dose two weeks later. However, in some, it is started with 80 mg followed by a 40 mg dose after two weeks. Thereafter, the usual dose during the ongoing treatment is 40 mg every other week. Some common side effects include pain or swelling, redness, bruising and itching at the injection site, pain, nausea, headache, fatigue, and joint pain. Some other side effects could be allergic reactions.

Other side effects include infections, such as the cold and flu, which may result in pneumonia and sepsis, greater risks of developing tuberculosis, or having underlying TB reactivated, blood problems, and liver problems, skin reactions, some types of cancer, new heart failures, or worsening of heart failure. Other rare complications include demyelization and some rare inflammatory conditions.

It has been revealed by researchers that adalimumab can be effective in bringing about and maintaining remission. It can also reduce the need of hospitalization and surgery. It can successfully treat fistulas. It can also be helpful when other drugs, such as infliximab, have failed.

Mercaptopurine

It is used to treat Crohn’s disease and ulcerative colitis. It comes as a tablet and an oral suspension to be taken by mouth. It is taken once a day. It should be preferably taken at the same time each day. If taking an oral suspension, then shake the bottle for 30 seconds. If taking an oral syringe, then measure accurately and take the dose. To treat ulcerative colitis, mercaptopurine is used. For its efficacy in Crohn’s disease, it is administered orally. It is also known as 6-MP. It is one of the most popular chemotherapy treatments used by Crohn's patients.

Meracptopurine interferes with the metabolic action, so it is classified as an anti-metabolic. Although it has certain side effects, it is used to treat Crohn’s disease.

These side effects can be too difficult to handle. Extreme ones include temporary reduction in white blood cell count and red blood cell count. This increases the risk of infection and anemia. The other side effects of this drug include nausea, vomiting, hair loss, rash, and darkening of the skin. Other side effects associated with mercaptopurine are shortness of breath, swelling in the legs, ankles, or feet, yellowing of the skin or eyes, swelling of the stomach area, pale skin, sore throat, unusual bruising or bleeding, loss of appetite, diarrhea, and pain in the upper right part of the stomach.

Mercaptopurine when combined with corticosteroids has shown efficacy in the treatment of Crohn’s disease. In steroid–naïve patients, use of this medication has been found to be effective. Despite continued therapy, relapses occur, but these relapses are easily treatable.

Immunosuppresants for Crohn's disease

They belong to the class of drugs that reduce or suppress the body’s immune system. They are also known as anti-rejection drugs. They are used to treat autoimmune disorders such as Crohn’s disease. In an autoimmune disease, the immune system of the body attacks its own body tissues, which causes inflammation.

Immunosuppressant drugs weaken the immune system, thus suppressing its reaction and also the inflammation response that causes Crohn's disease. Immunosuppresants help bring about and maintain remission and heal fistulas and intestinal ulcers caused by Crohn’s disease. For treating active disease flares, they are sometimes combined with corticosteroids. Thus, the immunosuppressive agents block the immune reaction that contributes to the inflammation in Crohn’s disease. Most of these agents have anti-MAP activity.