What are Immunosuppressant & Why are they important?
Immunosuppressants are drugs which damped down the immune system. They can also be called Immunomodulators; as they modify the immune’s response to a proposed threat to the body.
IBD is an auto immune disorder, in which the immune system over reacts to inflammation. The cause is still unknown, but treatment plans usually look to changing the body’s response to this inflammation. Immunosuppressants are a good way of helping control these responses; preventing too much damage occurring.
Why are they used to treat IBD?
Immunosuppressants can be appropriate in the following treatment situations:
- Non-response or intolerance to aminosalicylates, antibiotics, or corticosteroids.
- Steroid-dependent disease or frequent need for steroids.
- Perianal disease that does not respond to antibiotics.
- Fistulas; abnormal channels between two loops of intestine, or between the intestine and another structure – such as the skin.
- To bolster the effect of a biologic drug and prevent the development of resistance to biologic drugs.
- Prevent recurrence after surgery.
Common drugs under the umbrella of immunosuppressants to treat IBD are:
- Azathioprine – a 6-MP which is used a second line of treatment after 5 ASA’s have failed or a patient is steroid dependent. Special attention on the liver and its function needs to be taken whilst using this medication. This medication is taken orally as a tablet, but also comes in film coated version too.
- Mercaptopurine – also known as Puri-nethol, it is the purer form of Azathioprine. It’s particular chemical make up means for patients who react to Azathroprine or have increase liver function bloods, this is still an option as a 6-MP. This medication is taken orally as a tablet.
- Methotrexate – usually a chemotherapy drug to help reduce the immune system response, it is also used to add to the effectiveness of IBD biologics such as Infliximab. This medication can be given orally or as an injection. It is important to take folic acid with this medication too.
- Cyclopsporine – a medication that can weaken the immune system, it is used in mostly cases of UC within IBD as it works to treat acute flare ups of IBD, faster than Azathioprine and without a lengthy weaning off from steroids. This is taken as oral tablet.
How are they used to treat IBD?
Azathioprine & Merceaptopurine
The dose of these drugs will depend on your body weight and with the severity of your condition. You may be started on a low dose which is then increased gradually. Those with liver problems or the elderly will typically stay on a lower dose for the safety due to other conditions.
- Azathioprine: the usual dose is between 1.5 mg and 2.5 mg per kg of body weight per day.
- Mercaptopurine: the dose is usually half that of Azathioprine, ranging from 0.75 – 1.5 mg per kg of body weight per day.
Doses are also based on the levels of enzymes in your body that break down the drugs.
In general, Azathioprine tablets need to be taken with food and swallowed with a glass of water; while Azathioprine film coated tablets and Mercaptopurine tablets need to be taken with a glass of water one hour before or three hours after food.
Methotrexate is taken as a single once a week dose on the same day each week. It can be taken in two different ways – either by tablets or by injection. Sometimes people start off on the injection form, before moving to oral tablets.
• Tablets: taken by mouth, after food. The tablets should be swallowed whole with a glass of water while sitting upright or standing. Do not crush or chew them. They come as 2.5mg or 10mg tablets – but be aware both tablets look very similar so it is important to double-check your medication after receiving your prescription from your pharmacy.
• Injection: can be either subcutaneous (under the skin) or intra-muscular (into muscle). These can be given at the clinic by the nurse, or alternatively your nurse may train you to inject the methotrexate yourself.
Benefits of Methotrexate can take up between 8-12 weeks. It is also important to take the folic acid also prescribed along side the Methotrexate. Folic acid is a vitamin that can help your body cope with methotrexate and help reduce some of the possible side effects, such as nausea and vomiting. Usually it is taken once a week, but not on the same day as methotrexate. But a number of different regimes may be used, so it best to confirm this with your specialist if unsure.
Cyclosporin is given as IV in hospital and then oral gel filled capsules afterwards. The dose is given according to your weight usually in the range of 5-8mg per kilogram of body weight per day. The dose may be adjusted according to response and levels of drug in the body. Cyclosporin is also available as a liquid if you have problems swallowing the capsules. This medication needs to be taken twice a day, spaced evenly apart – example: 12 hours apart 0800 and 2000 – as this ensures the drug is evenly distributed throughout your body.
Side Effects & Important Information
- As these medications are immunosuppressants, it is important to note that they reduce the entire immune system, which means you are more likely to catch colds, the flu and viruses whilst taking these medications. It is important that you take sensible precautions to prevent infections whenever you can.
- All three immunosuppressants mention require pre-screening checks on the liver and kidney function before beginning treatment.
- You will need to have regular blood counts and liver tests while you are on immunosuppressants to check that the treatment is not affecting your blood or liver. A typical approach may be to have blood tests every 1-2 weeks for the first 2 or 3 months until therapy is stabilised, and then every 1-3 months thereafter. This can show whether you are developing side effects to the medication.
- Your treatment monitoring may be managed by your hospital team or shared between the hospital and your GP. You may be given a booklet to record your test results. Take this with you every time you see your GP, hospital doctor, dentist, specialist nurse or pharmacist, as sharing information helps you to receive safer care.
- If you are a woman it is important not to become pregnant while you or your partner are taking Methotrexate, as it can have serious effects on the unborn baby. You should stop taking Methotrexate at least six months before trying to conceive.
- Try to avoid close contact with people with infections. Methotrexate affects the way the body’s immune system works, which can make you more prone to infections. Even a mild infection, such as a cold or sore throat, could develop into a serious illness.
- Methotrexate can increase the skin’s sensitivity to sunlight, and the risk of developing some types of skin cancer. This can be reduced by wearing hats, light clothing and high SPF sun block.
- Avoid driving and hazardous work until you have learned how your treatment affects you, as these drugs can occasionally cause dizziness.
- Don’t take grapefruit or grapefruit juice for 1 hour before taking your Cyclosporin as it can increase the amount of medicine in your blood which could lead to more serious side effects.
Side effects from these medications can be:
- Nausea, or a flu-like illness with fever, and general aches and pains: especially at first, but this usually settles down once your body gets used to the drug.
- A sudden worsening of diarrhoea.
- Tingling of the hands or feet.
- Growth of hair on the face.
- Swollen gums: if this persists please see your dentist.
- Reduced kidney function (usually temporary) and a rise in blood pressure: these will be monitored in clinic, so attend all appointments.
- Less commonly, inflammation of the liver, and/or the pancreas (pancreatitis) or anaemia.
- Suppression of the bone marrow function which can lead to anaemia.
- A slightly increased risk of developing lymphoma (a type of cancer affecting the lymph glands). However, research suggests that for most people taking these drugs the risk is very small and likely to be outweighed by the potential benefits.
Your doctor should talk through the risks and benefits before you start Azathioprine, Mercaptopurine, Methotrexate or Cyclosporin. Let your doctor or IBD nurse know about any new symptoms you develop, whenever they occur.
NB: If you are worried about taking an immunosuppressant or you have any questions about your particular treatment, contact your doctor or IBD nurse. They should be able to help you with queries such as why it has been prescribed, what the correct dose and frequency is, what monitoring is in place, and what alternatives may be available for you.
For my Crohn’s disease I’ve taken three of these four immunosuppressants. You can read more about my experience with Azathioprine and Mercaptopurine here.
You can also read more about my experiences with Methotrexate here.
I ran a Twitter poll for this post, results can be found here.
Have you had to take any immunosuppressants for your IBD? Have you found them useful as a treatment option? Have you any experience with the side effects? Have you had success with them?
Crohn’s Colitis Foundation: Immunomodulators(pdf)
Jewish Digest: Drugs Used in IBD – Immunosuppressants
IBD Clinic: Immunosuppressants
Bradford Hospital: Ciclosporin for Servere Ulcerative Colitis (pamplet)
Crohn’s and Colitis UK: Methotrexate (pdf)
Crohn’s and Colitis UK: Azathiorprine (pdf)