Medications for IBD
IBD is a chronic disease that affects quality of life and can lead to complications including the need for surgery. Treatments are used both to reduce symptoms and improve quality of life in the short term and also to reduce long term complications and disability from the disease. Medications are the main-stay of treatment for IBD although other treatments including surgery may sometimes be required. IBD is a chronic and incurable disease and treatment is therefore often used long-term (for years or even decades). Whilst all medications have a risk of side-effects, not everyone will have side effects from treatment. In making treatment decisions we weigh up the individual risks of treatment against the risks of no treatment (including symptoms and potential complications of your disease). The treatments we use are proven to reduce inflammation, symptoms and complications including the need for surgery and improve quality of life for patients with IBD. The decision on which treatments to use is tailored to the individual circumstances.
The medications used to treat inflammatory bowel disease (IBD) are used for two broad purposes. The first is to get active disease under control (called remission). This is called induction. The second goal is to maintain disease in remission and prevent in from becoming active again (called relapse). This is called maintenance. Whilst treatment algorithms vary between the two main types of IBD, ulcerative colitis (UC) and Crohn’s disease (CD), the treatment goals are similar and the medications used are similar.
Ultimately the decision on how to manage your condition is yours. This page outlines some of the treatment options so that you can make an informed decision on how to manage your disease, minimize the chances of side effects and identify any side effects early. More detailed information is available at the time of consultation with your doctor and from a range of reliable websites including the Gastroenterology Society of Australia (GESA) website (www.gesa.org.au) and Uptodate® website which has patient information sheets that can be downloaded (www.uptodate.com).
There are particular issues surrounding medications for IBD and pregnancy and these should always be discussed with your specialist. Active IBD can reduce fertility and increase the likelihood of miscarriage and other undesirable outcomes of pregnancy (such as prematurity, low birth weight and birth defects). Keeping your disease under control during pregnancy is the most effective way to reduce the risks. Most medications for IBD (except methotrexate) should be continued during pregnancy and breast-feeding and it is not wise to stop treatment without first discussing this with your doctor. Please talk to your GP or specialist about this issue well before planning pregnancy.
5-Aminosalicylate (5-ASA) medications
5-ASA medications all contain the same active ingredient (Mesalazine) but vary in the way the drug is delivered to the target location in the gut. Medications from this class include Sulfasalazine, Pentasa, Mesasal, Mezavant, Colazide, Salofalk and Dipentum. Different formulations of 5-ASA can be administered orally or topically (rectally) as either liquid enemas or tablet-like suppositories. These medications are effective for both induction and maintenance in ulcerative colitis and are often the first class of medication used because they are effective, well tolerated and have a good safety profile. These medications are sometimes used in Crohn’s disease but are considered less effective.
5-ASA medications work directly on the surface of the gut and absorption into the body is limited. They reduce inflammation and symptoms of IBD and may also reduce the risk of cancer associated with IBD. Higher doses of 5-ASA medication are used for induction, often both orally and topically together. Once the disease is under control lower doses may be sufficient to keep the disease under control. Treatment with 5-ASAs may be the only treatment needed for ulcerative colitis and they are often continued for many years or decades.
The oldest medication from this class, Sulfasalazine, has a higher risk of side-effects, mainly related to the ‘Sulfa’ part of the medication. Headache is a fairly common side-effect but can be managed by reducing the dose. Rarer side-effects include inflammation of the liver (hepatitis), pancreas (pancreatitis), destruction of red cells (haemolysis), reduced sperm count in men (which is reversible), rash (which can be serious) and allergic reactions (particularly in those who have reacted to other sulfa drugs).
Side-effects from the other types of 5-ASA are rare and most patients tolerate treatment very well. Some patients may experience headaches or feel nauseous. Patients taking Dipentum can develop watery diarrhea. Rarer side-effects of 5-ASA medications include effects on the kidneys (nephritis), pancreas (pancreatitis), rash, hair loss, inflammation of the lung (pneumonitis) or the pericardium (pericarditis).
Steroids include conventional prednisolone/ prednisone, intravenous formulations such as hydrocortisone, synthetic formulations such as budesonide and topical or rectally administered formulations such as Colifoam, predsol and budenofalk enemas. Steroids are an effective and commonly used treatment for many conditions including inflammatory bowel disease. There are many potential side effects. Steroids are usually used for short periods of time (usually a couple of months) and usually starting at a high dose and slowly reducing over time. Although very effective, steroids have significant short-term and long-term side-effects. Generally speaking, the benefits of steroids reduce over time and the risk of side-effects increase.
We all depend on having some naturally produced steroid circulating to maintain essential bodily processes. While you are taking steroid medications the body will stop making the natural hormone and it takes the body a few days or even weeks to start producing the steroid again when treatment is stopped. For this reason it is very important that you do not stop steroid medications suddenly but slowly reduce the dose (weaning) to allow the body to start producing the natural hormone. Stopping the medication suddenly can be dangerous. You may feel faint, tired and have very low blood pressure. If this happens or you cannot take your medication for any reason (vomiting etc.) then you must contact your doctor straight away.
Although steroids are an effective short-term treatment for IBD they are not effective in long-term treatment. Many people with IBD will need long-term ‘maintenance’ treatment with a different medication to keep their disease from becoming active again. One of the goals of maintenance treatment is to reduce the need for steroid treatment. Usually you will need to start (or continue) your maintenance treatment during treatment with Prednisone and continue this treatment after the course of Prednisone is completed. If you need frequent courses of Prednisone or you cannot reduce the dose of Prednisone without your symptoms returning you may need to change your maintenance treatment.
The risk of side effects of steroids depends on what type of steroid, how it is administered, how high the dose is and how long you take the medication. Topical (rectal) treatments with suppositories or enemas generally have fewer systemic side-effects. The synthetic steroid budesonide (budenofalk, entocort) is quickly de-activated by the liver and so the risk of side-effects is lower.
Early Side Effects
Early side-effects may include:
- Mood changes and sleep disturbance
- Increased appetite
- Fluid retention and high blood pressure
- High blood sugar and diabetes
- Increased risk of infection
- Low salt (potassium) levels
- Muscle weakness
- Blurred vision
Long-Term Side Effects
Long term side-effects may include:
- Weight gain
- Loss of bone density leading to osteoporosis and increase risk of bone fractures
- Hair growth
- Thinning of the skin and easy bruising
- Damage to joints (avascular necrosis)
Although this is a concerning list of side-effects most patients will not experience serious side-effects and when used appropriately and with medical supervision most side-effects can be safely managed and are reversible (particularly in the short term). The decision to take steroids should be tailored to your circumstances and only when the benefits of treatment outweigh the risks.
The main immunomodulators (or conventional immunosuppressant medications) used in IBD are the thiopurines (Azathioprine and 6-Mercapto-purine or 6MP) and methotrexate. Other immunomodulators sometimes used include cyclosporine and tacrolimus.
Thiopurines are used in inflammatory conditions such as inflammatory bowel disease, rheumatoid arthritis and chronic autoimmune hepatitis. For inflammatory bowel disease (IBD) they are an effective long-term maintenance treatment. They are used to prevent ‘flares’ of disease and reduce the need for steroid treatments. As IBD is a life-long disease, usually treatment will be continued for a number of years and sometimes for many years to try and alter the course of the disease and prevent complications such as the need for surgery. The benefit of thipurines takes months to accrue and so you may need other treatment (such as steroids) to control your disease to give the thiopurine time to work. Usually we cannot say if the thiopurine is going to help or not for at least 3 months after you start treatment.
Most patients will tolerate these medications well but there is a risk of side effects, some of which are serious. To safely use these medications you will need to follow your doctor’s advice carefully. You will need frequent blood tests in the first few months of treatment and several times a year whilst you remain on treatment. The risk of side-effects from immunosuppression can be reduced by carefully following your doctors advice particularly with regard to ensuring you are up-to-date with vaccinations (but avoiding live vaccines), take care to protect your skin from UV radiation (with hats, long sleeves and sunscreen), have regular skin checks and regular blood tests to check your blood counts and liver function.
Side-effects of thiopurines include:
- Nausea and flu-like symptoms
- Bone marrow suppression
- Hepatitis and liver problems
- Rash and sun-sensitivity
- Increased susceptibility to skin cancer
- Abnormal cervical (Pap-) smears
- Cancer and Lymphoma
You must not (except under close medical supervision) take allopurinol (Progout – a treatment for gout) during treatment with thiopurines as there is a potentially dangerous interaction with this medication. The interaction with allopurinol is sometimes used to increase the effectiveness of thiopurine treatments (although with much reduced dose of the thiopurine). It is wise to always discuss any new medications with your doctor to avoid drug interactions.
Methotrexate is an immunomodulator that is sometimes used in inflammatory bowel disease, particularly in people who cannot take thiopurines. Methotrexate is also used in a number of other inflammatory conditions and also in high doses to treat some cancers. Methotrexate may be used as an injection under the skin or as tablets and for IBD it is taken once a week. It is usually given with Folic Acid a couple of days later to reduce side-effects. It is otherwise used in very similar ways to the thiopurine medications. Methotrexate must not be used during pregnancy as there is increased risk of miscarriage and a high risk of birth defects. People using methotrexate should use a reliable form of contraception. Methotrexate should be stopped by both men and women at least 3 months before conception.
Side-effects of low-dose methotrexate include:
- Nausea and stomach upset
- Mouth ulcers
- Liver problems and liver test abnormalities
- Headache, fatigue and reduced concentration
- Hair loss
- Inflammation of the lung (pneumonitis)
- Bone marrow suppression
Patients are often and understandably concerned about the risk of cancer and lymphoma but it is important to recognize that the risks are very small and mainly in people who have been on treatment for many years. The risks can be minimized with medical supervision. Generally speaking, the benefits of treatment outweigh the risks although this will depend individual factors (such as age, family history, extent and severity of disease, previous sun exposure). The relative risks and benefits of treatment may change for the individual over time. Please discuss any concerns with your specialist.
Biological agents are synthetic molecules that target parts of the inflammatory response implicated in the inflammatory process of IBD. The arrival of biologics is one of the most exciting developments in the treatment of IBD over recent years. The first group of medications released targeted the tumour necrosis factor (TNF) molecule (infliximab and adalimumab). Recently a new class of biologic targeting a different molecule (α4β7 integrin) has become available (vedolizumab).
Anti-TNF medications are generally well tolerated and effective against IBD but because of their mechanism of action and because the body can develop an immune reaction against the drug there are risks including reactivation or susceptibility to certain infections, inflammatory or allergic type reactions and there may be a modest increase risk of lymphoma and cancer. Before starting anti-TNF biologics you should be assessed for the risk of having latent infection (particularly tuberculosis) which can be re-activated by treatment. You may also be asked to have testing to rule out other latent infections.
Vedolizumab prevents the movement of inflammatory cells into the gut. Vedolizumab appears to have a very good safety profile although long-term data are not available. In data available so far the only increased risks identified (compared to no treatment) are an increased risk of mild nasal and sinus symptoms. There are ongoing concerns about a condition called progressive multifocal leukencephalopathy (PML) which occurs with a related medication (natalizumab) although at the time of writing no cases of PML had been reported in patients taking vedolizumab and due to the different mechanism there should not be an increased susceptibility to this condition.
Biologics are given by injection either into a vein (infliximab – which is given as an infusion in hospital) or under the skin (adalimumab and vedolizumab which can be self-administered at home). These medications are very expensive and the Pharmaceutical Benefit Scheme (PBS) will only subsidise the cost of treatment for patients meeting certain criteria of disease severity and usually those who have been unable to control their disease with conventional (steroid and immunomodulator) treatment. Once started on these treatments they can only be continued if they have adequate controlled your disease as assessed by your specialist. This requires monitoring of blood tests and regular re-assessment with your specialist.