Anti-Infliximab Antibodies Can Guide Treatment Intensification in Patients With CD

A study¹ published in Alimentary Pharmacology Therapeutics in December 2017 compared the outcomes, pharmacokinetics, and immunogenicity of treatment intensification strategies in patients with Crohn disease (CD) who have lost clinical response to the anti—tumor necrosis factor (anti-TNF) therapy infliximab.

The presence of antibodies towards infliximab (ATI) is associated with lower infliximab trough concentrations and loss of response. The authors note that infliximab treatment intensification is effective for most patients with Crohn disease (CD) to restore response, however.

The researchers conducted a retrospective cohort study comprising 103 patients with CD who had a loss of response during infliximab maintenance therapy, and who subsequently received a double dose (10 mg/kg), and/or a shortened interval between infusions. Infliximab and ATI concentrations were measured in consecutive trough samples, just before (T0) and just after (T+1) treatment intensification.

Overall, 37% of the patients did not respond to dose intensification. Patients with ATIs above 282 ng/mL at T0 were significantly less likely to achieve T+1 therapeutic drug levels. Conversely, drug levels at the time of loss of response were less correlated with the outcome of the intervention.

In a linked editorial², S. Ben-Horin, MD, sees these results as “underscoring once more the need to identify patients who will respond to dose optimization, while sparing this costly and potentially detrimental intervention from patients with low likelihood to respond.”

Ben-Horin also explains that the results of the study find that dose doubling is more effective in restoring a drug level of greater than 3 mcg/mL compared with interval shortening. Although the exact interval of dose shortening was not reported within the study, it could stand to reason that some patients may have had received an “every 6-week shortening” rather than interval halving, the latter of which the paper notes is comparable to dose doubling.

“Nonetheless, these data are in line with prior observations on overall non-inferiority of dose-doubling [versus] interval halving, and together they support double dosing over interval-shortening as a viable option which may save patients the need for another infusion visit and contribute to improved quality of life,” writes Ben-Horin.

The best strategy may ultimately be the prevention of loss of response by utilizing a proactive approach with drug and ATI measurements, among other factors.

“Data such as presented by Dreesen and colleagues are important for advancing our knowledge of how to implement pragmatic, yet rational-based approach to patients with [loss of response] to anti-TNFs.”

References

1. Dreesen E, Van Stappen T, Ballet V, et al. Anti-infliximab antibody concentrations can guide treatment intensification in patients with Crohn’s disease who lose clinical response. Published online December 11, 2017. Aliment Pharmacol Ther. doi: 10.1111/apt.14452.

2. Ben-Horin S. Editorial: restoring therapeutic infliximab drug levels in patients with loss of response- pharmacokinetics and anti-drug antibodies as useful guidance tools. Published February 18, 2018. Aliment Pharmacol Ther. 2018. doi: 10.1111/apt.14489.