Biologic therapy with the tumour necrosis factor inhibitors (TNF-α-inhibitors) infliximab or adalimumab appears to offer the most effective medical management of fistulising CD.
The infliximab study published in 1999 is the only randomised, controlled intervention study using a biologic agent with fistula response as primary end-point. In this study, 94 patients were randomised to either infliximab induction treatment, with infusion at 0, 2 and 6 weeks, or placebo, then infusion in week 14 and evaluation in week 18. Fistula response at two consecutive visits was 62 % in the treatment group and 26 % in the control group (4). The efficacy after 54 weeks of maintenance treatment was also investigated later. In one study, 306 patients received normal induction treatment until week 14, before being randomised for further treatment with 5 mg/kg every eight weeks or a placebo. Patients treated with infliximab had a higher rate of complete fistula response, with 36 % against 19 % (5).
Adalimumab also had some efficacy in a study of 117 patients treated for 56 weeks. The efficacy, measured as a reduction in the number of draining fistulae, was significantly higher in the treatment group after 26 weeks (33 % compared with 13 %) and the results persisted until week 56 (6). Certolizumab pegol is not approved for use with Crohn's disease in Norway, but in a sub-study of 54 respondents after 6 weeks on induction treatment, a significant fistula closure effect was noted after 26 weeks of treatment compared with a placebo (7).
Vedolizumab, a bowel-specific anti-integrin, has exhibited an anti-inflammatory effect in connection with Crohn's disease, and in a sub-analysis of 35 patients with fistulising CD, a significant difference in complete fistula response was found after 52 weeks of treatment, 41 % compared with 11 % for the placebo group (8).
Ustekinumab blocks interleukin 12 and 23. Its efficacy with fistulising CD has not been thoroughly investigated, but a Spanish cohort study with 18 fistula patients, 11 of whom had fistula response after ten months of treatment, indicates that this drug, too, may have some efficacy (9).
Pilot studies with local injection of infliximab or adalimumab in and/or around the fistula area have shown a response rate to fistulising CD of from 40 % to 100 % (10).