We are behind the curve when treating Crohn's disease

Dr John P Wright

There was a fundamental change in the management of Crohn's disease in 1990 when the value of immunosuppression with azathioprine was generally accepted. In 1998 the whirlwind of infliximab hit the profession after the FDA approved its use in an unusual fast track approval process. At last we had disease modifying drugs at our disposal. We should now be able to report that the rest is history!

Unfortunately this is not the case. Many patients continue to be treated by the old cortisone and more cortisone then cut and resect regimen. Some patients and, in particular children, continue to suffer with this approach.

The reasons for this sorry state of affairs are related to the cost of modern medication and the perceived dangers of therapy. Secondly there is often a belief, harking back to the early days of cancer surgery, that you can cure the disease by removing it surgically.

The only way to change this paradigm is to convince the primary physician that Crohn's disease is a medical condition that needs to be treated with disease modifying drugs. The term primary includes your family practitioner, medical physician and, surprisingly, gastroenterologist. Let us now look at their difficulties.

The cost of therapy cannot be denied. Azathioprine and blood tests will cost about R12 000 a year. At the end of the year only 40% of patients will be in remission. However virtually all patients given cortisone will relapse and have had significant side effects in the process. Recently it has been shown that the efficacy of azathioprine can be improved and toxic effects reduced by manipulating the dose on the basis of its metabolites.

When it comes to the new anti-TNF antibodies (Tumour Necrosis Factor Antibodies)) commonly called biologics, the costs escalate to about R120 000 a year. At present Revellex, Humira and Simponi are available. Biosimilar (Generic) versions are available for the first two agents, Remsima and Amgevita respectively. These reduce the price by about 20% so we can expect the annual cost to reduce to about R100 000. The relative efficacy and side effects of these new agents still need to be established.

Still these prices seems exorbitant until you compare the cost of hospitalization, surgery and sick leave. When this is calculated it has been shown that the total costs are more for similar patients not being treated with biologics. One has to remember that the intention of treatment is to place the patient in complete clinical remission.

Although the major medical aids have accepted the cost benefit of the biologics, others and particularly the smaller medical aids do not. Private patients need to be given this advice to change their medical aid, if necessary, at the time of diagnosis. Unfortunately the public sector is showing no sign of accepting the biologics as standard therapy. This is very worrying if the current standards of care are forced on all citizens in the proposed new nationalized system.

The next problem with moving our treatment regimens forward is the perceived dangers of the anti-TNF drugs. The most serious problem is that TNF, which these drugs neutralize, is an important part of the bodies’ defence against tuberculosis. In weighing up the risks one needs to consider the benefits of the medication versus the tuberculosis rate in the patient group that you are treating. Whereas anyone can be infected with tuberculosis or re-activate old disease, not all patients have the same risk of this. Likewise Crohn's disease can occur in anyone but generally it is the middle and upper income strata that are affected more commonly. It is nevertheless critical to test annually for tuberculosis exposure with history, chest X ray and initially blood or skin tests. An initial test for hepatitis B infection is also recommended.

The risk of malignancy developing in Crohn's disease patients on anti-TNFs is thought to be very low especially compared to the risks of not treating. On a similar vein the danger of intestinal cancer developing in patients with inflammatory bowel disease has always been a risk and fear. This risk is related to the extent and activity of the gastrointestinal disease. As these modern anti-TNF drugs reduce the inflammation to levels that cannot be easily be detected the associated cancer risk is dramatically reduced. This may be the most important factor supporting the use of biological therapy in patients with inflammatory bowel disease.

Finally there is surgery where the primary role is to remove fibrotic strictures in the small bowel. Active disease is best treated medically and that includes swollen ileal loops and fistula. Biologics are the primary treatment for penetrating/fistulating disease. Abscess formation in severe disease is common. Fortunately perforation and generalised peritonitis as one sees in appendicitis does not often occur in Crohn's disease. This means that with a biologic to control the Crohn's disease, antibiotics to treat the infection and intravenous feeding to maintain the patient, even traditionally severe ileocolonic disease can be managed medically.

In summary the standard of medical management of Crohn's disease has leaped forward over the last few years. Our primary physicians need to hear the message.