Niels Vande Casteele1, Marc Ferrante2, Gert Van Assche2, Vera Ballet2, Griet Compernolle1, Kristel Van Steen3, Steven Simoens4, Paul Rutgeerts2, Ann Gils1, Séverine Vermeire5. 1. Department of Pharmaceutical and Pharmacological Sciences, Laboratory for Therapeutic and Diagnostic Antibodies, KU Leuven-University of Leuven, Leuven, Belgium. 2. Department of Gastroenterology, University Hospitals Leuven, KU Leuven-University of Leuven, Leuven, Belgium. 3. Systems and Modeling Unit, Montefiore Institute, University of Liège, Liège, Belgium; Bioinformatics and Modeling, GIGA-R, University of Liège, Sart-Tilman, Belgium. 4. Department of Pharmaceutical and Pharmacological Sciences, Clinical Pharmacology and Pharmacotherapy, KU Leuven-University of Leuven, Leuven, Belgium. 5. Department of Gastroenterology, University Hospitals Leuven, KU Leuven-University of Leuven, Leuven, Belgium. Electronic address: severine.vermeire@uzleuven.be.
Abstract
BACKGROUND & AIMS:Infliximab, a tumor necrosis factor antagonist, is effective for treating patients with Crohn's disease (CD) and ulcerative colitis (UC). We aimed to determine whether dosing based on therapeutic drug monitoring increases rate of remission and whether continued concentration-based dosing is superior to clinically based dosing of infliximab for maintaining remission in patients with CD and UC. METHODS: We performed a 1-year randomized controlled trial at a tertiary referral center, including 263 adults (178 with CD and 85 with UC) with stable responses to maintenance infliximab therapy. Doses were escalated or reduced using an algorithm to reach a target trough concentration (TC) of 3-7 μg/mL in all patients (optimization phase). Patients were randomly assigned (1:1) to groups that received infliximab dosing based on their clinical features (n = 123) or continued dosing based on TCs (n = 128) (maintenance phase). The primary end point was clinical and biochemical remission at 1 year after the optimization phase. RESULTS: At screening, 115 of 263 patients had a TC of infliximab of 3-7 μg/mL (43.7%). Of 76 patients with TCs <3 μg/mL, 69 patients (91%) achieved TCs of 3-7 μg/mL after dose escalation. This resulted in a higher proportion of CD patients in remission than before dose escalation (88% vs 65%; P = .020) and a decrease in the median concentration of C-reactive protein, compared with before the dose increase (3.2 vs 4.3 mg/L; P < .001); these changes were not observed in patients with UC. Of 72 patients with TCs >7 μg/mL, 67 patients (93%) achieved TCs of 3-7 μg/mL after dose reduction. This resulted in a 28% reduction in drug cost from before dose reduction (P < .001). Sixty-six percent of patients whose dosing was based on clinical features and 69% whose dosing was based on TC achieved remission, the primary end point (P = .686). Disease relapsed in 21 patients who received clinically based dosing (17%) and 9 patients who received concentration-based dosing (7%) (P = .018). CONCLUSIONS: Targeting patients' infliximab TCs to 3-7 μg/mL results in a more efficient use of the drug. After dose optimization, continued concentration-based dosing was not superior to clinically based dosing for achieving remission after 1 year, but was associated with fewer flares during the course of treatment. ClinicalTrialsRegister.eu number: 2011-002061-38.
RCT Entities:
BACKGROUND & AIMS:Infliximab, a tumornecrosis factor antagonist, is effective for treating patients with Crohn's disease (CD) and ulcerative colitis (UC). We aimed to determine whether dosing based on therapeutic drug monitoring increases rate of remission and whether continued concentration-based dosing is superior to clinically based dosing of infliximab for maintaining remission in patients with CD and UC. METHODS: We performed a 1-year randomized controlled trial at a tertiary referral center, including 263 adults (178 with CD and 85 with UC) with stable responses to maintenance infliximab therapy. Doses were escalated or reduced using an algorithm to reach a target trough concentration (TC) of 3-7 μg/mL in all patients (optimization phase). Patients were randomly assigned (1:1) to groups that received infliximab dosing based on their clinical features (n = 123) or continued dosing based on TCs (n = 128) (maintenance phase). The primary end point was clinical and biochemical remission at 1 year after the optimization phase. RESULTS: At screening, 115 of 263 patients had a TC of infliximab of 3-7 μg/mL (43.7%). Of 76 patients with TCs <3 μg/mL, 69 patients (91%) achieved TCs of 3-7 μg/mL after dose escalation. This resulted in a higher proportion of CDpatients in remission than before dose escalation (88% vs 65%; P = .020) and a decrease in the median concentration of C-reactive protein, compared with before the dose increase (3.2 vs 4.3 mg/L; P < .001); these changes were not observed in patients with UC. Of 72 patients with TCs >7 μg/mL, 67 patients (93%) achieved TCs of 3-7 μg/mL after dose reduction. This resulted in a 28% reduction in drug cost from before dose reduction (P < .001). Sixty-six percent of patients whose dosing was based on clinical features and 69% whose dosing was based on TC achieved remission, the primary end point (P = .686). Disease relapsed in 21 patients who received clinically based dosing (17%) and 9 patients who received concentration-based dosing (7%) (P = .018). CONCLUSIONS: Targeting patients' infliximabTCs to 3-7 μg/mL results in a more efficient use of the drug. After dose optimization, continued concentration-based dosing was not superior to clinically based dosing for achieving remission after 1 year, but was associated with fewer flares during the course of treatment. ClinicalTrialsRegister.eu number: 2011-002061-38.
Authors: Orlaith B Kelly; Morgan Rosenberg; Andrea D Tyler; Joanne M Stempak; A Hillary Steinhart; Zane Cohen; Gordon R Greenberg; Mark S Silverberg Journal: J Crohns Colitis Date: 2015-12-30 Impact factor: 9.071