Some of the views expressed in the following notes on newly approved products should be regarded as preliminary, as there may have been limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Executive Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.
vials containing 100 mg as lyophilised powder
Approved indication: Crohn's disease
Australian Medicines Handbook Section 14.1.4
Crohn's disease causes chronic inflammation in the gastrointestinal tract. With time it tends to respond less well to treatment and many patients will develop complications such as a fistula. The cause of the disease is unknown, but an immune mechanism may be involved. Patients with Crohn's disease produce increased amounts of tumour necrosis factor alpha (TNF-alpha). This factor may be responsible for inducing the mucosal inflammation.
Animal studies found that inflammation can be reduced by antibodies to TNF-alpha. Infliximab is a monoclonal antibody which neutralises TNF-alpha in humans. It was studied in a randomised controlled trial of 108 patients with moderate to severe Crohn's disease. Four weeks after a single infusion, 65% of the patients given infliximab had a clinical response compared with only 17% of the patients given a placebo. The disease went into remission in 33% of the infliximab group but only 4% of the placebo group.1
Another study investigated 94 patients with abdominal or perianal fistulas. These patients were given an infusion of infliximab or a placebo. This infusion was repeated two weeks and six weeks later. The number of draining fistulas decreased by half in 62% of the infliximab group compared with 26% of the placebo group. In 46% of the infliximab group the fistulas healed, while only 13% of the placebo group had an absence of any draining fistulas.2
Infliximab is a human form of a mouse monoclonal antibody produced using recombinant techniques. Approximately 16% of patients will have a reaction to its infusion. They may develop urticaria, fevers and chills. Some patients experience falls or rises in blood pressure so it is important that they are observed during and after the two hour infusion. Patients who develop antichimeric antibodies are more likely to have infusion reactions. These antibodies could also alter the pharmacokinetics of infliximab. The half-life of infliximab is normally about 10 days and it takes up to six months for serum concentrations to become undetectable.
Approximately 5% of patients withdrew from clinical trials of infliximab because of adverse events. Apart from infusion reactions adverse effects include headache, nausea, vomiting and abdominal pain. The patients given infliximab developed more infections than patients given a placebo. Although infliximab does not cause a generalised suppression of the immune system, caution is needed particularly if the patient has been taking immunosuppressive drugs for their Crohn's disease. It is unclear if infliximab increases the risks of developing lymphoproliferative disorders. Some patients will develop autoantibodies and cases of a lupus-like syndrome have been reported.
More information is needed on the long-term effectiveness of infliximab. In the short-term study the proportion of patients with a clinical response after 12 weeks had declined and the number of patients in remission was not significantly different from placebo.1 If symptoms recur the treatment can be repeated within 14 weeks. Readministration after this period is currently not recommended because of the risk of delayed hypersensitivity reactions.
Recombinant products tend to be expensive. Infliximab is therefore reserved for patients who have not responded to conventional therapies for moderate to severe Crohn's disease.
- Crohn's disease cA2 Study Group. A short-term study of chimeric monoclonal antibody cA2 to tumor necrosis factor a for Crohn's disease. N Engl J Med 1997;337:1029-35.
- Present DH, Rutgeerts P, Targan S, Hanauer SB, Mayer L, van Hogezand RA, et al. Infliximab for the treatment of fistulas in patients with Crohn's disease. N Engl J Med 1999;340:1398-405.