123Several recent studies have attempted to assess the clinical efficacy of proactive
TDM, all with infliximab. Cheifetz and colleagues evaluated 48 patients who had
undergone proactive TDM [ 51 ]. Twelve of these 48 required escalation therapy,
whereas 15% required dose reduction. Compared to a control cohort of 78 patients,
the monitored group had a significantly lower rate of infliximab discontinuation
(HR 0.3, 95% CI 0.1–0.6). The likelihood of remaining on infliximab was highest
for those with a trough IFX concentration >5 μg/mL, but similar results were seen
with a cutoff level of 3 μg/mL.
Proactive TDM has also been assessed by two randomized controlled trials. In the
TAXIT trial, patients with IBD in stable clinical response on infliximab (95% of
whom were on infliximab monotherapy) received initial dose optimization to attain
infliximab levels of 3–7 μg/mL [ 52 ]. After dose modification (if necessary), patients
were then randomized to either proactive TDM with target infliximab level 3–7 μg/mL
(which also allowed for dose de-escalation) or drug dosing based on increased clinical
symptoms or CRP. Although remission rates at 1 year were nearly identical between
the two groups, it is important to note that rates of remission were significantly higher
in patients with CD after initial dose intensification than prior to dose intensification,
thus implying that TDM had a beneficial effect. Also, all patients were initially opti-
mized with TDM and followed subsequently for up to only 1 year, which may not be
long enough to appreciate a difference. In addition, the proactive TDM group was
significantly less likely to have flared than their counterparts (7% vs. 17%, p = 0.018).
Costs of therapy were also significantly reduced in the proactive TDM arm.
The other randomized controlled trial, TAILORIX, which is currently pub-
lished only in abstract form, included 122 patients with active CD who were
randomized to one of three strategies after standard IFX induction at 5 mg/kg: (1)
a dose increase by 2.5 mg/kg based on drug levels, clinical symptoms, or bio-
markers, (2) similar monitoring with a dose increase to 10 mg/kg, or (3) dose
intensification to 10 mg/kg [ 53 ]. There was no significant difference in individu-
als without ulceration (47% vs. 38% vs. 40%, respectively) or mucosal healing
(51% vs. 65% vs. 40%, respectively) at 54 weeks. However, when examining the
percentage of individuals who had sustained IFX levels >3 μg/mL at each time
point during the 54 weeks of follow- up, the third group undergoing reactive mon-
itoring had the highest persistently therapeutic drug levels (60%) compared to
either the first proactively monitored group (47%) or the second group (46%). As
such, these results are somewhat difficult to interpret.
Future Directions: TDM for Biologic Therapies in IBD
With respect to infliximab and adalimumab, for which there are much available data
regarding TDM, there are still a number of important data gaps. First, it is unclear
what levels should be measured to most accurately assess the drug: trough, peak, area
under the curve, time above a minimum threshold, etc. Second, it is likely that differ-
ent patients will have different thresholds for remission, based on other factors, such
8 Therapeutic Drug Monitoring of Biologic Agents