Cumulative Exposure to Infliximab, But Not Trough Concentrations, Correlate With Rate of Infection

Amandine Landemaine (1) , Antoine Petitcollin (2) , Charlène Brochard (2, 3) , Céline Miard (1) , Marie Dewitte (1) , Eric Le Balc'H (1) , Thomas Grainville (1) , Eric Bellissant (2) , Laurent Siproudhis (2, 3) , Guillaume Bouguen (2, 3)

1 Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Ponchaillou]
2 CIC - Centre d'Investigation Clinique [Rennes]
3 NuMeCan - Nutrition, Métabolismes et Cancer

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.

Mots clés: CD; anti-TNF; treatment; tumor necrosis factor

Domaines: Sciences du Vivant [q-bio]; Hépatologie et Gastroentérologie

Amandine Landemaine, Antoine Petitcollin, Charlène Brochard, Céline Miard, Marie Dewitte, et al.. Cumulative Exposure to Infliximab, But Not Trough Concentrations, Correlate With Rate of Infection. Clinical Gastroenterology and Hepatology, 2021, 19 (2), pp.288-295.e4. ⟨10.1016/j.cgh.2020.03.018⟩. ⟨hal-02533415⟩