Assessing the role of ustekinumab dose escalation in Crohn's disease patients with loss of response: an observational study.

Abstract

Background/aims: Among Crohn's disease patients with loss of response or non-response to ustekinumab (UST), there remains no clear strategy for dose escalation. Moreover, clinical associations and the role of therapeutic drug monitoring (TDM) are poorly understood. This study assessed response to escalation of UST therapy via increased dosing frequency or re-induction, as well as assessed associations of response.

Methods: A single-centre retrospective cohort study was performed. Adults who underwent dose escalation to every 4 weeks or reinduction of UST were included. The primary outcome was clinical and biochemical remission which was defined as a Harvey Bradshaw Index (HBI) of <5 and a C-reactive protein (CRP) level within the normal limit or a Fecal Calprotectin (FCP) level <250 ug/g. Partial response to treatment was defined as a 50% decrease from baseline HBI, CRP, or FCP.

Results: Thirty-nine patients were included. Clinical outcomes were assessed at a median of 17 weeks (IQR 12-21). Clinical and biochemical remission was achieved in 30.8% of patients (n = 12). Remission was found to be more likely among patients with lower baseline HBI (5.2 vs 9.0 P = .044) and younger patients (29.8 years vs 37.7 P = .046). No association was observed between baseline TDM values in the remission vs the non-remission group (3.32 ug/mL vs 2.91 ug/mL p=0.77). No severe adverse events were recorded.

Conclusion: UST dose escalation, in the form of reinduction or increased frequency to every 4 weeks may be effective among patients with loss of response or partial response, though predictors of response and strategy of escalation remain unclear.