Chronic uncontrolled inflammation of the digestive tract can lead to symptoms, poor quality of life, malnutrition, and many complications, such as fistulas, strictures, loss of nutrients, and even cancer. There are many medications and your doctor will choose the one that works for you.
The risks and benefits of taking medications and controlling disease need to be carefully considered. Each medication has potential side effects, but great benefits. Speak to your gastroenterologist about your options for treatment.
Approach to Medical Therapy for IBD
IBD are chronic diseases, and most people with IBD require maintenance (long term) medication to keep them in remission. The two main treatment approaches are the “STEP up” strategy and the “TOP down” strategy.
In the STEP up treatment strategy, clinicians will prescribe milder drugs that have less side effects, and increase doses or add stronger medications or more targeted medications when patients flare, and when patients require repeated courses of steroids. When medications no longer work, or when there are complications of the IBD, surgery may be advised. Clinical trials are considered the “next, next” line therapy once existing and approved therapies fail.
In the TOP down approach, clinicians will often start with stronger drugs that will control the disease faster or with more success, often starting with targeted therapies (e.g. biologics) or immunosuppressants, and in some cases with clinical trials or surgery.
Categories of IBD Medications
The main categories of IBD medications are listed below (click on link to read more about each category):
5-aminosalicylates (5-ASA)
What are 5-ASA?
These are mesalamine containing compounds, with very few side effects.
e.g. Asacol, Mesavant, Pentasa, Salofalk.
Who uses 5-ASA?
5-ASA are most commonly used to treat ulcerative colitis, although some patients with Crohn’s colitis may find benefit.
How are 5-ASA taken?
They can be taken orally once to several times a day.
There are topical forms (liquids, foams, suppositories that melt) which were made to coat the inner lining of the rectum and last part of the colon.
The topical therapies may help with healing of the rectum (and help with the symptoms of urgency, rectal bleeding).
Immunosuppressants
What are immunosuppressants?
These are medications designed to suppress or modify the immune system.
Remember to do your regular blood work as you increase the doses of these medications to reach your regular maintenance dose.
What is Methotrexate?
Methotrexate can be taken as oral tablets OR injections and is dosed WEEKLY.
Methotrexate is a teratogen (causes malformed fetus and miscarriage) and should be stopped at least 3 to 6 months BEFORE attempting to conceive).
Steroids
What are steroids?
These are medications that suppress the inflammation, but have many side effects.
e.g. prednisone, budesonide.
Budesonide has two formulations (Budesonide CR (Entocort® ) and Budesonide MMX (Cortiment®) which have less to no side effects compared to prednisone due to being less systemic (Budesonide CR is ileal release and MMX releases into the colon). These appear to be safe to use in pregnancy.
Can steroids be used long term?
Steroids are NOT meant for long term use, they are NOT maintenance medications.
Steroids have too many side effects and should be tapered as soon as possible.
How are steroids taken?
Steroids can be oral tablets OR intravenous (in hospital administration).
Steroids also come in topical (enemas or suppositories) form for distal colitis.
What are the side effects of steroids?
Mood changes
Facial puffiness
Hair growth
Weight gain
Skin changes
Increased risk of infections
Increased pressure in the eyes (glaucoma) or change sin the lens (cataracts)
Bone loss (osteoporosis) or bone death (avascular necrosis)
High blood pressure (hypertension) and danger of low blood pressure if the medication is stopped abruptly
High blood sugar (diabetes)
Inflammation or ulcers in the stomach
Biologics
What are biologics?
These are medications that are designed to specifically target a protein or a pathway of the inflammatory and immune responses.
There are currently 4 categories of biologics – they all work by binding and blocking the effects of inflammatory proteins (cytokines), receptors (when cytokines bind receptors, they trigger further inflammatory pathways), or white blood cells (inflammatory cells).
α4β7 are proteins found on white blood cells. MAdCAM1 are proteins found on the gut blood vessel walls. In order for the white blood cells to enter the gut tissue, their α4β7 protein has to bind to the MAdCAM1 proteins.
Vedolizumab blocks the binding of α4β7 to MAdCAM1 thus blocking some of the white blood cells from going into the gut (blocks leukocyte or white blood cell trafficking).
Anti-interleukin (anti IL-23) – risankizumab (Skyrizi®) and mirikizumab (Omvoh®)
IL-23 cytokines cause inflammation when they bind to their receptors.
these biologics block the binding of the receptors and thus stops/reduces inflammation caused by IL-23 cytokines.
How are these given?
These are given by intravenous infusions (IV), subcutaneous (injected through the skin) injections (SC), or a combination of IV and SC.
Induction: these drugs require an induction period (meaning more frequent and higher doses of drugs at the beginning) in order to get the “drug level” high enough.
Maintenance: once you have the first induction doses, if the drug works, you will be kept on a schedule of every 1, 2, 3, 4 or more weeks depending on response to the drug and type of drug. It is very important not to skip or be late for doses, otherwise you can develop antibodies (proteins that block the drug) and lose the effect of the drug.
What is a drug level?
Drug level refers to the amount of the drug in your blood – scientists and clinicians have studied the range of drug level that controls inflammation.
Individual people and different diseases types may require different minimum drug levels to get into and stay in remission.
What is an antibody level?
Antibody is a protein that blocks something else – so an antibody to the biologic drug is protein your body makes that blocks the drug.
This can cause issues such as losing response to the drug, or developing reactions to the drug.
Your doctor may prescribe an immunosuppressant such as Imuran or Methotrexate in order to lower the chances of you developing antibodies to the biologic drugs.
The chances of you developing an antibody to the drug is higher if you have missed doses or delayed doses.
Small Molecules
What are small molecule drugs?
Small molecule drugs are NOT proteins, they are drugs with a chemical structure.
Currently (2024) the small molecule for IBD include the JAK (Janus Kinase) inhibitors, and Sphingosine-Phosphate-1 (S1P) modulators.
What are small molecule drugs used for treatment of IBD?
JAK inhibitors – Tofacitinib (Xeljanz®) and Upadacitinib (Rinvoq®) are Health Canada approved JAK inhibitor for treatment of ulcerative colitis (both of them) and Crohn’s disease (Upadacitinib). JAK inhibitors work on the JAK-STAT pathway and block various inflammatory pathways.
S1P modulators – Ozanimod (Zeposia®) is used for treatment of ulcerative colitis. S1P modulators are thought to work by blocking the lymphocyte trafficking out of the lymph glands.
How are small molecule drugs taken? What kind of monitoring is required?
These are oral pills taken once or twice daily depending on which one.
People taking JAK inhibitors should have regular blood work for – blood counts, liver tests, cholesterol.
People taking S1P modulators should have regular blood work, and may require certain screening (e.g. eyes and hear) before starting.
IBD medications can be induction (to get you better quickly) or maintenance (long term medication to keep you well). Please note that steroids are not meant to be maintenance medications due to the many many side effects associated with taking steroids long term.
What About IBD Medications and Pregnancy?
Most IBD medications can be continued during pregnancy, however Methotrexate should be stopped before and during pregnancy. JAK inhibitors and S1P modultors should be stopped before and during pregnancy.
Click here for more information about IBD medications and pregnancy.
