Higher Infliximab Trough Concentrations Needed for Mucosal Healing in Crohn’s Disease Than Previously Suggested

Higher Infliximab Trough Concentrations Needed for Mucosal Healing in Crohn’s Disease Than Previously Suggested

Monika Fischer, MD, reviewing Dreesen E, et al. Clin Gastroenterol Hepatol 2020 Jan 16.

The previously published TAILORIX study failed to show benefits from proactive therapeutic drug monitoring (including drug trough concentrations, biomarkers of inflammation, and patient symptoms measured at regular intervals) over infliximab dose escalation dictated only by symptoms in patients with ileocolonic Crohn’s disease. This post hoc analysis of the TAILORIX study looked at whether serum concentrations of infliximab and concentrations of biomarkers were associated with endoscopic healing during the remission induction (12 weeks) and maintenance phases (54 weeks). 

Infliximab trough levels >23.1 mg/L at 2 weeks and >10 mg/L at 6 weeks predicted endoscopic healing at 12 weeks. In the maintenance phase, infliximab serum concentrations >10.6 were associated with absence of ulcers at 54 weeks. Persistently elevated fecal calprotectin following dose escalation predicted therapeutic failure. Fecal calprotectin <250 mg/kg was associated with absence of ulceration on endoscopy. In responders, fecal calprotectin concentrations decreased quickly, within 8 weeks following dose escalation, but symptom response was often delayed and became apparent only after 3 infusions given at the escalated dose. The authors concluded that the combination of calprotectin and infliximab trough concentrations can guide dose adjustment and improve chances of endoscopic healing.

COMMENT
While current guidelines suggest infliximab trough concentrations >5 mg/L may induce endoscopic remission, data from the TAILORIX study suggest that we should aim for levels >10 mg/L at 6 weeks and any time thereafter during the maintenance phase. Since fecal calprotectin reliably predicted response following dose escalation, it can be used to monitor response to therapy every 4 to 8 weeks. If calprotectin remains high, antibodies to infliximab should be measured to understand the mechanism of failure and inform decisions on therapy changes.

Monika Fischer, MD, FASGE 

CITATION(S )

Cheng YW, Phelps E, Nemes S, et al. Fecal microbiota transplant decreases mortality in patients with refractory severe or fulminant Clostridioides difficile infection. Clin Gastroenterol Hepatol 2020 Jan 7. (Epub ahead of print) (https://doi.org/10.1016/j.cgh.2019.12.029

Ähnliche Beiträge

VOR
Nach oben scrollen