Infliximab Dose to Level Study in Patients with Pediatric Crohn’s Disease
Supervisor / Principle Investigator:
MD Class of 2020
Introduction/Objectives: Infliximab (IFX) is shown to be well-tolerated and effective for induction and maintenance of remission in Crohn's disease (CD). The main objective of this prospective observational study was to evaluate the relationship between IFX serum levels during induction therapy and short-term clinical outcome in children with CD
Methods: Conducted at the Stollery Children’s Hospital, Hospital for Sick Children, and Manitoba Children’s Hospital, baseline data were collected including disease classification (Paris classification) and clinical activity [Weighted Pediatric Crohn’s Disease Activity index (wPCDAI)]. The induction IFX dose was prescribed by the treating physician ranging from 5mg-10mg/kg. Dose adjustments and time between infusions were optimized by the physician based on patient clinical response, laboratory results and previous drug trough levels. Up to a total of 8 IFX levels per patient were collected: trough and peak levels at the IFX infusions #2 and #4 (Visit 3 and 4), trough levels at Visits 5, 6 and 7, and trough level at Visit 8 (prior to IFX infusion #5). 3 antibodies to infliximab (ATI) levels, fecal calprotectin, wPCDAI, CBC diff, liver function tests, albumin, ESR and CRP were also collected at each infusion.
Results: 35 patients were recruited and followed for up to 22 weeks over 8 study visits. 81.3% went into clinical remission by infusion 5. Median dose for IFX infusion 1 was 6.0 mg/kg (IQR: 5.0-7.0) and increased to 7.0mg/kg (IQR: 5.0-8.25) for infusion 5. Trough and peak levels were not statistically correlated with clinical remission at all time points except for the trough level at infusion 5 with lower levels for patients in clinical remission (p=0.036). ATI drawn at baseline, infusion 4 and infusion 5 were all negative. 80% of patients were dose optimized and did not follow the standard infusion regimen of week 0, 2,6 and 14 weeks. Based on therapeutic drug monitoring, dose 4 had the most variability in infusion frequencies, but the median dose frequency was shortened to Q6W. Shorter infusion interval prior to infusion 4 was associated with higher wPCDAI at infusion 3 (r = -0.403, p = 0.016). Increase in IFX dose at infusion 4 was associated with lower IFX trough level at infusion 3 (r = -0.373, p = 0.03). There was also a positive correlation between IFX clearance and FCP at dose 1 (p = 0.026), ESR at dose 1 (p = 0.047) and 5 (p = 0.044) and wPCDAI at dose 4 (p = 0.027) and frequency at dose 4 (p = 0.001).
Conclusion: There was no statistical difference between trough levels except at infusion 5. However, most patients were dose optimized and went into clinical remission by infusion 5. ATI levels were negative and all patients had detectable IFX levels, which suggests that early dose adjustment may reduce the risk of ATI formation.