Rate of Ustekinumab Dose Escalation in Patients With Crohn’s Disease Who Had a History of Anti-TNF Dose Escalation

Background: Dose escalation of anti-tumor necrosis factor (anti-TNF) therapy is not uncommon in patients with Crohn’s disease (CD); transition to another therapy may be necessary if there is inadequate response despite dose escalation. There are limited data on rates of dose escalation of ustekinumab (UST) in CD patients who had a history of dose escalation on anti-TNFs, e.g., infliximab (IFX) and adalimumab (ADA). We sought to explore this relationship and to describe the ability to recapture response to UST dose escalation. Methods: This was a retrospective cohort study using medical records from adult patients with CD receiving UST who had a history of IFX or ADA treatment. Dose escalation was defined as an increase in IFX dosing from 5 mg/kg to 10 mg/kg or increase in frequency to every 4-6 weeks, ADA frequency increase to every week, and UST frequency increase to every 4-6 weeks. We measured concomitant thiopurine and steroid use, inflammatory markers, and Harvey-Bradshaw Index (HBI) at 0, 12, 16, and 20 weeks. Ability to recapture response was measured by a HBI decrease of at least 3 points between weeks 0 and 20. Additional data included patient demographics, Crohn’s phenotype, location, and duration of disease, related surgical history, and prior medications. Results: Of 105 patients, 37 patients (40.5% female, median age 32 years [range, 20-69]) with anti-TNF dose escalation were identified. All 37 patients were transitioned to UST. The rate of UST escalation in these was 18.9% (p=.001). Of those transitioned to UST, 48.6% were on concomitant medications at the start of UST therapy and 14.3% had adequate response to UST dose escalation therapy. Prior history of surgery (71.4%; p=0.03) and male gender (57.1% male; p=0.01) were associated with increased risk for UST escalation. There was no significant association between risk for UST dose escalation and disease duration, duration of UST therapy, reason for escalation, IBD phenotype, or location of disease. Conclusions: In those with a prior history of anti-TNF escalation, 18.9% had subsequent UST dose escalation. However, only a small number of these patients were able to recapture response to escalation. Prior history of surgery and male gender were associated with increased risk for UST dose escalation. This study suggests that close to one in five patients with a history of anti-TNF escalation may require dose escalation with UST. Further studies in a larger prospective cohort are required to validate these findings.