Proactive infliximab optimisation using a pharmacokinetic dashboard versus standard of care in patients with Crohn’s disease: study protocol for a randomised, controlled, multicentre, open-label study (the OPTIMIZE trial)

Abstract

IntroductionPreliminary data indicates that proactive therapeutic drug monitoring (TDM) is associated with better outcomes compared with empiric dose escalation and/or reactive TDM, and that pharmacokinetic (PK) modelling can improve the precision of individual dosing schedules in Crohn’s disease (CD). However, there are no data regarding the utility of a proactive TDM combined PK-dashboard starting early during the induction phase, when disease activity and drug clearance are greatest. The aim of this randomised, controlled, multicentre, open-label trial is to evaluate the efficacy and safety of a proactive TDM combined PK dashboard-driven infliximab dosing compared with standard of care (SOC) dosing in patients with moderately to severely active CD.Methods and analysisEligible adolescent and adult (aged ≥16–80 years) patients with moderately to severely active CD will be randomised 1:1 to receive either infliximab monotherapy with proactive TDM using a PK dashboard (iDose, Projections Research) or SOC infliximab therapy, with or without a concomitant immunomodulator (IMM) (thiopurine or methotrexate) at the discretion of the investigator. The primary outcome of the study is the proportion of subjects with sustained corticosteroid-free clinical remission and no need for rescue therapy from week 14 throughout week 52. Rescue therapy is defined as any IFX dose escalation other than what is forecasted by iDose either done empirically or based on reactive TDM; addition of an IMM after week 2; reintroduction of corticosteroids after initial tapering; switch to another biologic or need for CD-related surgery. The secondary outcomes will include both efficacy and safety end points, such as endoscopic and biological remission, durability of response and CD-related surgery and hospitalisation.Ethics and disseminationThe protocol has been approved by the Institutional Review Board Committee of the Beth Israel Deaconess Medical Center (IRB#:2021P000391). Results will be disseminated in peer-reviewed journals and presented at scientific meetings.Trial registration numberNCT04835506.

Editorial: proactive anti‐TNF drug monitoring in IBD—Ready for prime time?

“…Is there a window of opportunity to substantially improve the efficacy of a proactive TDM strategy using an i‐Dose‐assisted pharmacokinetic dashboard combined with proactive TDM to better drive dosing and maintain therapeutic drug levels? Results from the randomised, controlled, multicentre, open‐label trial OPTIMISE (NCT04835506) are awaited 7 …”

Association Between Plasma Rituximab Concentration and the Risk of Major Relapse in Antineutrophil Cytoplasmic Antibody–Associated Vasculitides During Rituximab Maintenance Therapy

“…Overall, this PK-guided dosing approach may allow for an improvement in clinical outcomes and quality of life while decreasing the financial toxicity for healthcare systems. The OPTIMIZE trial is ongoing to test this approach for infliximab dosing optimization in patients with Crohn's disease (30). Before the implementation of such a strategy with RTX in AAV patients, our PK/PD results need to be externally validated in a large cohort of patients.…”

Recent Advances in the Optimization of Anti-TNF Treatment in Patients with Inflammatory Bowel Disease

“…If applied earlier to guide accelerated IFX induction dosing, a PK dashboard may improve drug durability and immunogenicity [ 108 ]. In the meantime, an RCT is ongoing (the OPTIMIZE trial) also focusing on the induction phase, with the aim of assessing remission rates and the need for rescue therapy from week 14 through to week 52 in patients with moderate-to-severe CD initiating IFX and comparing the proactive TDM dashboard-driven dosing with the normal standard of care [ 109 ].…”