The unmet need in Crohn's disease is the limited effectiveness of current treatment options. Although tumour necrosis factor (TNF)-alpha-targeted biological agents is significantly better than placebo in inducing and maintaining remission in Crohn’s disease, primary non-response remains 19-58% in real-world studies. Effectiveness of anti-TNFs, however, demonstrate half of all patients commencing on anti-TNF will stop treatment by 2 years. Failure of ant-TNF biological agents over time is due to the high rate of immunogenicity and treatment emergent adverse events. Patients and physicians also may elect to stop anti-TNF treatment due to concerns over risks of serious complications and cost of ongoing biological agent use may be a barrier.

In deciding which biological agent is selected in the management of Crohn’s disease, persistence research is gaining ground as an important decision-making process. The Persistence Australian IBD National Cohort (PANIC) database is a real-world registry of patients on biological agents with prospectively collected data of ongoing therapy. Failure of treatment that leads to discontinuation of use is an endpoint of lack of effect, development of serious adverse outcomes or decision to stop treatment based on potential harm. In Australia, biological agents are reimbursed in Crohn’s disease with CDAI >300 following failure of conventional therapies. There is no hierarchical order of use permitting non-TNF-alpha targeted biological agents to be used first-line if deemed appropriate. These data demonstrate that in bio-naïve patients with Crohn’s disease, ustekinumab and vedolizumab have the highest treatment persistence versus TNF-alpha targeted treatments. In patients exposed to prior biological agents, ustekinumab remains the drug with the highest persistence. First-line biological agents have the highest persistence versus non-first line treatments. Anti-TNFs persistence significantly increases when combined with either thiopurines or methotrexate. In fistulising Crohn’s disease, the persistence of infliximab is similar to adalimumab. All biological agents demonstrate efficacy in achieving the targets outlined in the STRIDE-II guidelines. Vedolizumab is most likely to achieve the desired treatment targets when used early in Crohn’s disease, when commenced as the first-line biological agent and some data demonstrate higher trough levels may be associated with increased remission rate. Whether dose interval reduction achieves an incremental benefit in improving outcomes in patients on vedolizumab, however, is less clear. The addition of a week-10 infusion of vedolizumab in Crohn’s disease is recommended for higher-severity Crohn’s disease and in those with prior treatment failures. Lower endoscopic activity (SES-CD 7-15) also appears to achieve higher remission rates than higher SES-CD for vedolizumab. The benefit of vedolizumab remains its positive safety signal.