What are the risks of developing bowel cancer when receiving biological infusions to treat IBD?
Our honorary medical director - Dr Richard Hansen - answers this question.
Dr Hansen is a Consultant Paediatric Gastroenterologist and Honorary Clinical Associate Professor, Glasgow Children’s Hospital.
Great question! Most of the families with a member on biologic drugs (infliximab or adalimumab usually) will be aware of the increased risk of cancer attributed to these drugs. This is one of the trickiest things for IBD doctors and nurses to address, trying to explain or describe this risk in a way that makes some sense. I tend to use two different approaches in my own practice - first explaining the “see-saw” of risk and benefit, trying to remove consideration of risks/side-effects on their own and to ensure that these are seen against the hopeful benefits of therapy… healing the bowel, gaining weight, avoiding surgery, returning to school, etc. This is the only way to get some context about risk and to understand the whole picture.
The other thing I tend to do is explain how this risk comes about - immunosuppressants reduce the function of the immune system. That’s their job. I like to call this “turning down the volume” of the immune system, which still does its usual job on immunosuppressant drugs but slightly slower and with slightly less capacity than normal… meaning “normal” infections can take a little longer to resolve or might be a bit worse in severity than with a fully functioning immune system.
The other job the immune system does is to monitor our own body cells, eliminating those that look abnormal. This is an important step in preventing cancers before they can even develop and is called immune surveillance. It’s probably here that the increased cancer risk attributed to some immunosuppressant therapies comes from. If immunosuppressants work by turning down the volume of the immune system, this will have an impact on its normal job, notably in fighting infection and in immune surveillance. The net effect will be more infections that are worse in severity and last longer plus a small increase in cancers compared to the general population. Again, understanding all of this has to include considering the effect or benefit of the therapy and the alternatives available. This is the part that needs an understanding of the bigger picture.
So, let’s put some meat on the bones of the risk side of this discussion. I’ll do so with reference to two scientific papers. First, Kopylov and colleagues looked at 41,176 adult IBD patients in a Canadian database to explore drugs prescribed and cancers diagnosed. 19,852 were eligible to analyse against the questions the researchers were interested in. This particular study did identify an increased risk of non-melanoma skin cancers in patients receiving immunomodulator medicines for more than 5 years, but found no increase in melanoma skin cancer or colorectal cancer associated with IBD immunosuppressant therapies.
Remember, colorectal cancer is very much an adult diagnosis, so no finding in a large adult study is very reassuring for paediatric practice where the rates of this type of cancer are already vanishingly low. Second, Hyams and colleagues published an international paediatric experience paper, looking at 5,766 children being followed for longterm outcomes of IBD. In total 15 patients developed a cancer. 8 were leukaemia or lymphoma and 7 were of other assorted types. None was a colorectal cancer. Numbers like this are hard to comprehend on an individual basis, particularly when there is a baseline risk in the normal population. The authors helpfully included a table to help stratify risk a little better. The expected rate of cancer in the general (US) population of a similar age was 2.2 in 10,000 patients in a year. This rate increased to 2.4 with biologics alone, to 5.2 with thiopurine drugs (azathioprine and mercaptopurine) and to 7.0 with a combination of biologics and thiopurines.
This makes sense, as the pathway to colorectal cancer involves inflammation of the gut lining leading to cell changes and ultimately cancer. Controlling inflammation with immunosuppressant drugs is arguably more likely to reduce than increase this risk, but exploring all of this in a medical condition where inflammation in the bowel is a crucial feature is a difficult undertaking. The types of cancers seen on IBD therapy seem to involve the immune system more than other organs, but are still rare. Weighing up this risk for an individual must take into account the benefits of the therapy being used and the alternatives possible. This is a discussion to be had between individual families and their IBD teams. Hopefully this answer has given some reassurance and information for such discussions.
Kopylov U, et al. https://academic.oup.com/ibdjournal/article/21/8/1847/4602940
Hyams JS, et al. https://www.gastrojournal.org/article/S0016-5085(17)30148-8/abstract