**13.4 Clinical application**

From the limited information available, HSTCL seems to be linked to previous prolonged thiopurine exposure and the risk may be higher in those who have also received an anti-TNF drug. This seems to compete with conclusions drawn from recent efficacy trials. The SONIC trial found that combination therapy with azathioprine and infliximab reached significantly higher rates of steroid-free clinical remission than either of these drugs as monotherapy for a cohort of naïve patients with moderate to severe Crohn's disease (24.1% vs 34.9% vs 46.2% AZA vs IXB vs AZA+IXB at 50 weeks) (Colombel et al., 2010).

Whilst it is not possible to estimate the relative risk of HSTCL in IBD patients, Kotlyar et al attempted to derive the absolute risk of HSTCL in men using epidemiology data from the US and Europe as well as an estimate of thiopurine use in IBD patients from the French CESAME trial (Beaugerie et al., 2009a, Kotlyar et al., 2010). The group concluded that more than 99.99% of patients in immunomodulatory treatment will not develop HSTCL. Further reassurance comes from the CESAME study in that no cases of HSTCL were found despite analysis of over 50,000 patient-years follow up.

A vigilant approach must be taken when using thiopurines for the treatment of male patients under 35 years. Kotlyar et al recommended careful monitoring in patients who have been on thiopurine treatment for more than 2 years but this may be difficult to put in to practice as no pre-malignant markers have been identified. Decisions between the use of combination or monotherapy must be made in the context of clinical severity of disease and poor prognostic markers for complicated IBD. The risk of HSTCL is extremely low and patients should be made aware of this when making choices regarding their treatment. Highly efficacious therapeutic strategies should not be rejected based entirely on the low risk of HSTCL. Somewhat reassuringly, despite the rapidly increasing number of patients on anti-TNF drugs, exceeding 5 million patient-years exposure, the rate at which new cases of HSTCL have been diagnosed has not changed over the last 15 years.
