Dr John Wright



Side effects and dangers associated with the treatment of Crohn’s Disease and Ulcerative Colitis

Dr John P Wright
Updated: 31 July 2017

The management of inflammatory bowel disease has undergone a major metamorphosis over the past 20 years. The previous public image of patients with chronic diarrhoea, malabsorption and in need of frequent surgery, lingers on in spite of the use of modern medication which has made all of these dreadful associations simply untrue in the vast majority of patients. The main drivers of these previous poor perceptions were the overzealous use of prednisone and the belief that surgery could cure the diseases.

It remains a sad fact that prednisone continues to be widely used. The reasons for this are related to its cheapness, rapid clinical action and a temporary feeling of euphoria and improved well-being. The latter patient benefits have made some patients addicted to prednisone. The truth however is that long-term use of prednisone is a silent killer. Osteoporosis, skin damage, weight gain and diabetes are often irreversible.

Whereas surgery to treat a mechanical problem such as gastrointestinal obstruction is an excellent choice for that specific problem. These diseases are generalized autoimmune diseases and are not cured by intestinal resection. They are medical conditions which, pending better understanding of the actual cause, are best treated with modern drugs which change the underlying pathology.

We are just emerging from the first phase of modern therapy ie the use of anti-TNF drugs. There are currently 3 examples in use, Revellex/Remicaide, Humira and Simponi. If these are used soon after diagnosis a rapid response rate of 90% can be expected. Some patients may take longer to go into remission, ie no signs of disease, but the vast majority will be infinitely better within a few months.

The next question is at what cost? Financially these agents are a challenge. In the state health sector chances are slim as the annual allocation of drug is limited so prednisone and surgery remain the default. In the private sector, you will need insurance at the higher levels to have guaranteed access. The monthly cost of these agents is about R 10 000.00. The plus side is no or minimal symptoms, less other tests such as x-rays and endoscopies, no extra sick leave or missing school and essentially a normal lifestyle. A normal sex life and fertility are added bonuses. Often difficult to justify the price it has remained almost constant for the last 15 years.

The second question is what are the side effects and dangers? Firstly though, what are the side effects and dangers of not treating. To those with these diseases the need for proper treatment is clear. These are unpleasant, humiliating and socially unacceptable diseases. Treatment is desperately needed.

If prednisone is to be avoided what are the alternatives. The next level of therapy is the immunomodulator drugs, azathioprine and methotrexate. In brief azathioprine has a 3% chance of inflammation of the pancreas. This settles as soon as the drug is stopped but cannot be ever taken again. Another 3% have nausea and just do not feel well. The remaining 96% have no problems. Women on the drug can now go through pregnancy in spite of earlier concerns. The second alternative, methotrexate has less serious side effects. A fear of liver damage was much discussed but is hardly ever seen these days. The drug will however cause foetal abnormalities and is not usually used in potentially pregnant women or their spouses. In the big picture, however these two useful drugs are simply a stepping stone to the modern biological drugs mentioned above (Revellex/Remicaide, Humira and Simponi.)

Having arrived at the stage where these modern biologics are needed, how safe are they? Firstly, in pregnancy, the FDA (Food and Drug Administration of the USA) grade them as “B” which is as safe as penicillin and safer than a paracetamol headache tablet. More seriously, the main danger is with tuberculous infections. Our bodies control and inactivate the tuberculous bacteria with the help of TNF (Tumour Necrosis Factor). In South Africa, we have an epidemic of tuberculosis partly related to HIV infections. It is therefore critical that all patients are screened for this infection. If there is any suggestion that the infection is present somewhere in their bodies a full course of anti-tuberculous therapy is given. An annual check also needs to be made on every patient while on anti-TNF therapy.

Other potential infections need to be screened for. These include Hepatitis B, Epstein Barr (Glandular Fever) and chickenpox virus immunity. If there has been no previous exposure vaccinations can be given. Yellow fever vaccination at this time is also useful.

After infections what is the risk of developing a malignancy / cancer? In truth, it is very low. No-one knows for certain. All the medication used and the diseases themselves add to the risk of developing a malignancy. Some diseases such as colon cancer which is a risk in patients with ulcerative colitis may have a lower risk if their disease is kept inactive so modern therapy may reduce their chances of developing colon cancer. One thing that is apparent is that multiple immunosuppressive drugs have an accumulative risk. It is therefore prudent to reduce the number of drugs taken if possible. Similarly stopping these drugs after a period of remission makes good sense. That the disease may flare is well recognised but re-exposure to these agents appears to have the same beneficial effect as when originally used, so a break in exposure to these drugs may be a good idea.

This brings us to the second phase of modern therapy. There are new agents about to be marketed that stop the inflammatory cells accumulating in the bowel. These do not have the immunosuppressive qualities of the anti-TNF agents. Pending their release in the next year or two, the anti-TNF drugs remain the standard therapy of Crohn’s Disease and Ulcerative Colitis. As long as the measures mentioned above are taken they are safe and dramatically effective. All suitable patients should be on these agents.