Infliximab and Ustekinumab Clearance Better Predict Endoscopic Outcomes Than Trough Concentrations in Crohn's Disease.

Korte inhoud:BACKGROUND & AIMS: Infliximab and ustekinumab clearance have been suggested as predictors of disease activity in patients with inflammatory bowel diseases. We aimed to investigate the benefits of clearance monitoring for predicting endoscopic outcomes in patients with Crohn's disease (CD). METHODS: Data from patients with moderate-to-severe CD starting infliximab (n = 108) and ustekinumab (n = 80) therapy were repurposed. Endoscopic remission (CD Endoscopic Index of Severity <3) was assessed at week (w)12 and w54 of infliximab therapy. Endoscopic response (>50% reduction in Simple Endoscopic Score for CD) was assessed at w24 of ustekinumab therapy. We performed Bayesian forecasting to estimate time-varying mAb clearance using drug concentrations, covariates, and in-house developed population pharmacokinetics models. RESULTS: Patients achieving endoscopic remission at w12 had significantly lower infliximab clearance and higher infliximab serum trough concentrations (Ctrough) at w2 of standard 5 mg/kg infliximab induction therapy, than patients without endoscopic remission (P < .05). During infliximab maintenance therapy (with eventual dose optimizations), patients achieving endoscopic remission at w54 had significantly lower infliximab clearance (P < .001) but not higher infliximab Ctrough (P = .92) than those without remission. Moreover, infliximab clearance during maintenance had similar discriminative ability as fecal calprotectin (area under the receiver operating characteristics curve 0.63; 95% confidence interval, 0.56-0.69 vs 0.67; 95% confidence interval, 0.61-0.73, respectively). Ustekinumab clearance, but not Ctrough, was significantly different between endoscopic responders and nonresponders during standard ustekinumab induction and maintenance therapy (P < .05). CONCLUSIONS: Although Ctrough loses its ability to predict treatment response when doses are optimized or not administered by bodyweight, infliximab and ustekinumab clearance remains a reliable predictor for endoscopic outcomes.

Jaar van publicatie:2025

Trefwoorden:Algemene en interne geneeskunde

Toegankelijkheid:Closed

Reviewstatus:Peerreview