High infliximab exposure needed for radiologic remission in Crohn’s disease

Patients with active luminal Crohn’s disease (CD) are likely to achieve radiologic response and remission with infliximab trough level of 7.8 µg/ml at the end of induction therapy, as indicated by data from the TAILORIX trial.

A continuous high infliximab exposure (>5 µg/ml at all time points) is associated with radiologic response, according to the investigators. But patients with dose adjustments may need to maintain trough levels of >7 µg/ml. 

“Although proactive therapeutic drug monitoring is not supported by robust evidence at this stage, our results do suggest that optimal induction dosing could improve the outcomes of the patient,” they said, highlighting the need for a higher drug-exposure to attain radiologic remission. [Clin Gastroenterol Hepatol 2020;18:637-646.e11; Gastroenterology 2018;154:1343-1351.e1; Gastroenterology 2015;148:1320-1329.e3; Clin Gastroenterol Hepatol 2016;14:550-557.e2]

They analysed baseline and week 54 magnetic resonance enterography (MRE) data from 36 patients (median age 35.7 years, 50 percent female, median disease duration 1.5 months) with active luminal CD treated with infliximab in the TAILORIX trial. The MREs were scored using the Magnetic Resonance Index of Activity (MaRIA), with radiologic response and remission defined as scores below 11 and 7, respectively.

The radiological response and remission rates at week 54 of treatment were 36.4 percent and 30.3 percent, respectively. Meanwhile, endoscopic remission occurred in a much higher proportion of patients (71 percent). [Clin Gastroenterol Hepatol 2021;19:947-954.E2]

Both radiologic response and remission were tied to infliximab trough level at week 14 (p=0.049 and p=0.048, respectively).

The optimal week-14 trough level cutoff value for predicting radiologic remission over time was of 7.8 μg/mL (area under the curve, 0.74). It had 75-percent sensitivity, 86-percent specificity, 90-percent negative predictive value (NPV), and 57-percent positive predictive value (PPV).

At the same cutoff, the ability of infliximab trough level at week 14 to predict radiologic response was also strong (area under the curve, 0.73). The sensitivity was 70 percent, specificity was 90 percent, NPV was 86 percent, and PPV was 78 percent.

Radiologic response at week 54 also correlated with continuous pharmacologic evidence of response (infliximab trough levels >5.0 μg/mL at all time points; p=0.034).

More difficult target

“This is the first study to confirm the exposure–response relationship of infliximab for radiologic remission,” the investigators said.

“At baseline there was a correlation between the endoscopic and radiologic disease activity, which is in line with prior observations for MaRIA and other MRE scores. At week 54, however, there was a striking disconnect between endoscopic and radiological remission, suggesting that [the latter] is a more difficult target to reach,” they explained. [AJR Am J Roentgenol 2019;212:W25-W31]

They acknowledged that while difficult to achieve, radiologic healing can happen for patients with luminal CD. This is encouraging, as radiologic remission has been implicated in favourable clinical long-term outcomes. [Aliment Pharmacol Ther 2019;49:1026-1039; Aliment Pharmacol Ther 2018;48:1232-1241; Inflamm Bowel Dis 2017;23:1403-1409]

As such, the investigators reiterated the importance of monitoring trough levels of infliximab to guide treatment as well as optimizing dosing during the induction phase.