Efficacy of dashboard driven dosing of infliximab in inflammatory bowel disease patients; a randomized controlled trial

Abstract

Objectives: Loss of response (LOR) to infliximab (IFX) remains a challenge in the management of inflammatory bowel diseases (IBD). Proactive dosing strategies to achieve and maintain predefined IFX trough levels (TL) may prevent LOR. We aimed to investigate the efficacy of dashboard driven IFX dosing compared to standard dosing in a prospective trial in IBD patients.

Methods: In this multicentre 1:1 'PRECISION' trial, we randomized IBD patients in clinical remission (Harvey Bradshaw Index ≤4 for Crohn's disease (CD) or a partial Mayo score ≤2 for ulcerative colitis (UC)) receiving IFX maintenance treatment. The precision group (PG) received IFX dosing guided by a Bayesian pharmacokinetic model, aiming to achieve and maintain a TL of 3 µg/ml by treatment (de)escalation as indicated by the dashboard. Patients in the control group (CG) continued treatment without dose adaptations. The primary endpoint was the proportion of patients in sustained clinical remission after 1 year.

Results: Eighty patients were enrolled (66 CD, 14 UC), and the median [interquartile range] age was 37 years [27-51]). After one year, 28/32 (88%) of patients in the PG were in sustained clinical remission versus 25/39 (64%) in the CG (p = .017). PG patients had lower median faecal calprotectin levels after 1 year (p = .031), whereas no significant differences in median CRP levels were found.

Conclusion: We demonstrated that the use of a Bayesian dashboard for IFX dosing in maintenance treatment for IBD reduced the incidence of LOR compared to standard dosing. Precision dosing also resulted in lower FCP levels.

Clinicaltrials.gov number: NCT02453776.

Keywords: Therapeutic drug monitoring; anti-TNF; gastroenterology; pharmacokinetics.