02 June 2021
New(er) and emerging treatments in IBD
Sometimes people are concerned about commencing newer ‘more powerful’ medication to treat their IBD. Older drugs, such as Azathioprine and Methotrexate, are often the first line of treatment in Crohn’s Disease and the second line in Ulcerative Colitis (after they have failed Mesalazine or similar drugs). They can be successful, but there are some concerns over their longer term safety, and the efficacy data is not as good as some of the newer medications.
You might be offered some of the newer drugs if Azathioprine or Methotrexate are no longer working, you are suffering from side effects or you have concerns about co-existing health issues, the longer term risks or are planning to get pregnant.
Current biologics available
- Infliximab blocks the actions of TNF (tumor necrosis factor alpha) in the body. TNF causes tissue inflammation which leads to pain, diarrhea, fatigue and other symptoms.
- It’s used in moderate-severe inflammatory and perianal Crohn’s and moderate-severe Ulcerative Colitis.
- It is given as an intravenous infusion week 0, 2 and 6, then every 8 weeks. This makes for a very convenient method of treatment, as patients only need to come in once every 2 months for treatment.
- There are some side effects related to Infliximab, which include infusion reactions, bacterial infections, serum-sickness and drug-induced lupus.
- In June 2021 Infliximab will be available in Australia as a 2 weekly subcutaneous injection.
- Adalimumab works the same was as infliximab, blocking the actions of TNF.
- It’s used in moderate-severe inflammatory and perianal Crohn’s and moderate-severe Ulcerative Colitis, and where there has been previous infliximab failure or intolerance.
- Given by subcutaneous injection, there are 2 loading doses 2 weeks apart (with 4 injections at week 0 and 2 injections at week 2), then given by a single injection every 2 weeks.
- Side effects include injection site reaction and infections of the respiratory tract or urinary tract, and rarely serious infections.
- Vedolizumab stops inflammatory cells from entering the lining of the gut, which is a more targeted approach than anti-TNF drugs which works on the entire body.
- It’s used in moderate-severe inflammatory Crohn’s, moderate-severe Ulcerative Colitis, and in elderly patients or those with concerns about immunosuppression.
- Similar to Infliximab, it’s given as an intravenous infusion at week 0, 2 and 6, followed by 1 infusion every 8 weeks.
- Side effects are limited and include a slight increase in the risk of gut infections. It may not be as effective for Crohn’s Disease compared to Ulcerative Colitis.
- In July 2021 Vedolizumab will be available as a 2 weekly subcutaneous injection.
- Ustekinumab is one of the newer drugs available, and works differently to Infliximab, Adalimumab and Vedolizumab. It works by blocking the actions of IL-12 and IL-23, two inflammatory proteins (cytokines) in the body.
- It’s only used in mild-moderate inflammatory Crohn’s, and not yet approved for use in Ulcerative Colitis or perianal Crohn’s. It can be used in elderly patients, and patients with previous failure or intolerance to Infliximab and Adalimumab.
- The first dose of Ustekinumab is given by intravenous infusion, then via subcutaneous injections every 8 weeks, making it a convenient treatment.
- As with any medication there are some side effects, including injection site reactions and the risk of infection. It can also take longer to work compared to Infliximab and Adalimumab, but potentially has a lower risk of infection. It also appears to be safe during pregnancy.
Emerging medications: small molecule drugs
More recently there have been some newer medications called small molecule drugs. They have a low molecular weight and because they are smaller than antibody medications such as Infliximab they can pass through the cell membranes. They are given orally rather than intravenously or subcutaneously. They work by blocking pathways within the cell.
Tofacitinib (Xeljanz ®)
- Tofacitinib is currently only used in Ulcerative Colitis. It is an oral medication taken twice a day and is fast acting in its results.
- Given it is a newer medication there is limited long-term safety data, but side effects include increased lipid levels, potentially higher rates of influenza, nasopharyngitis and other infections, DVT and shingles. It is also uncertain whether it is safe to take during pregnancy and breastfeeding.
Future and trial medications
Ozanimod is a small molecule drug that may soon be listed on the PBS for Ulcerative Colitis. Trials are currently being conducted on Crohn’s Disease.
It is given orally once daily and is fast acting.
As it is a newer medication long term safety data, including during pregnancy, is unknown. Side effects include minor infections, headaches and elevated liver enzymes. However, there seems to be less cardiovascular side effects compared to other non-specific S1P inhibitors.
Etrolizumab is a monoclonal antibody, designed to target and block two proteins involved in the immune response.
It is used in mild-moderate inflammatory colonic Crohn’s and mild-moderate Ulcerative Colitis, as well as elderly patients and those with a previous Infliximab or Adalimumab failure or intolerance.
Given by subcutaneous injections every 4 weeks, it is a convenient method of treatment.
Side effects include rash and injection site reactions. It takes longer to work compared to Infliximab and Adalimumab, and it’s safety in pregnancy is currently not known.
It’s important to understand what medications are available for you, and your gastroenterologist can work with your symptoms and treatment side effects to find the most effective options for you.
Contributed by Paul Spizzo