SummaryBackgroundThere are limited data concerning infliximab drug monitoring during de‐escalation of the treatment of inflammatory bowel disease (IBD).AimTo define the rate and the predictors of relapse following infliximab de‐escalation in IBD patients in remission.MethodsAll IBD patients at a single referral centre in clinical and biological remission and in whom the dose of infliximab had been de‐escalated were included. Patients in remission with a high trough level of infliximab (>7 mg/L) were considered to be trough level‐based de‐escalation patients. The data were retrieved from a prospective IBD database. Actuarial analysis was performed for statistical purposes.ResultsA total of 146 de‐escalations were performed in 96 patients (Crohn's disease/ulcerative colitis: 68%/32%); 54 (37%) were based on clinical remission only, and 92 (63%) were based on clinical remission associated with a trough level above 7 mg/L. The cumulative probabilities of relapse following infliximab de‐escalation were 16% and 47% at 1 and 2 years, respectively. Ulcerative colitis was associated with an increased risk of relapse (HR = 3.2, P = 0.005). Conversely, combination therapy at infliximab initiation (HR = 0.39, P = 0.0110) and trough level‐based de‐escalation were associated with decreased risk of relapse (HR = 0.45, P = 0.024). Trough levels before and after de‐escalation were well correlated; a decrease by half was observed following a 2‐week interval increase or a half‐dose decrease.ConclusionThe use of trough levels to assess the feasibility of dose de‐escalation seems to be a prerequisite for decreasing the risk of relapse.

Background & Aims: Infliximab increases the risk of infection in patients with inflammatory bowel diseases (IBD), but there is controversy over the relationship between drug concentration and infections. We aimed to assess factors associated with infection in infliximab-treated patients, including pharmacokinetic features. Methods: We collected data from 209 patients with IBD (102 men; mean age, 39 y; 159 with Crohn's disease; 54 received combination therapy) who received a infliximab maintenance regimen from November 2016 through April 2017 in France. Data were collected from each infusion visit (total of 640 infusions). Infliximab exposure was estimated based on the area under the curve (AUC) of drug concentration in pharmacokinetic models; individual exposures over the 6-month period were estimated based on the sum of the AUC (ΣAUC). Results: The mean infliximab trough level was 5.46 mg/L, and the mean ΣAUC was 3938±1427 mg d/L. A total of 215 infections were collected from the 640 infusion visits; 123 patients (59%) had at least 1 infection. Factors independently associated with infection after multivariate analysis were smoking (odds ratio [OR], 2.05; P=.046), IBD flare (OR, 2.71; P=.006), and a high ΣAUC of infliximab (above 3234 mg x d/L) (OR, 2.02; P=.02). The ΣAUC was higher in patients with an occurrence of infection (P=.04) and correlated with the number of infections (P=.04). Trough concentration of infliximab alone was not associated with infection. Conclusions: Almost two-thirds of patients treated with infliximab developed an infection; risk was individually correlated with cumulative increase in drug exposure, but not infliximab trough level.

Therapeutic strategies for perianal fistulizing CD require robust anatomical and healing evaluations. Combined strategies using biologics to improve both drainage and secondary closure of the fistula tracts merit further study.