Postinduction serum infliximab trough level and decrease of C-reactive protein level are associated with durable sustained response to infliximab: a retrospective analysis of the ACCENT I trial.
BACKGROUND
Serum infliximab trough levels correlate with efficacy; dose escalation is often beneficial in patients with Crohn's disease who stop responding to infliximab treatment.


OBJECTIVE
To carry out a post hoc analysis of A Crohn's Disease Clinical Trial Evaluating Infliximab in a New Long-term Treatment Regimen I (ACCENT I) to evaluate the association between serum infliximab trough levels and C-reactive protein (CRP) after 14 weeks of induction treatment with durable sustained long-term response (Crohn's Disease Activity Index decrease ≥70 points and reduction ≥25% from baseline).


METHODS
ACCENT I was a multicentre, randomised, placebo-controlled study. Week 14 trough levels and CRP percentage decrease from baseline to week 14 were compared between patients with and without durable sustained response through week 54. Sensitivity and specificity were determined to predict durable sustained response. Receiver operating characteristic (ROC) curves identified optimal cut-off points; logistic regression determined ORs.


RESULTS
After induction with 5 mg/kg infliximab, 25% (37/147) and 33% (47/144) of patients sustained week 14 response to infliximab 5 or 10 mg/kg, respectively, administered every 8 weeks without dose escalation, through week 54. Median week 14 trough levels of patients with and without durable sustained response to infliximab 5 mg/kg were 4.0 and 1.9 μg/mL, respectively (p=0.0331). Optimal predictors of durable sustained response to maintenance infliximab 5 mg/kg were week 14 trough level ≥3.5 µg/mL and ≥60% CRP decrease (ORs (95% CI), 3.5 (1.1 to 11.4) and 7.3 (1.4 to 36.7)), respectively, in patients with raised baseline CRP (>8.0 mg/L); area under the ROC curve was 0.75 for both predictors. A ≥3.5 µg/mL week 14 infliximab serum level did not predict durable sustained response to 10 mg/kg maintenance infliximab.


CONCLUSIONS
Patients with durable sustained response to maintenance infliximab 5 mg/kg had higher postinduction trough levels than patients without durable sustained response. Serum infliximab trough levels ≥3.5 µg/mL and ≥60% CRP decrease were significantly associated with durable sustained response.
Department of Immunology, Janssen Biologics BV, Leiden, The Netherlands.
Freddy
F
Cornillie
Departments of Gastroenterology, Hepatology, and Nutrition, The University of Chicago Medicine, Chicago, Illinois, USA.
Stephen B
SB
Hanauer
Medical Group, Janssen Biotech, Inc, Horsham, Pennsylvania, USA.
Robert H
RH
Diamond
Biostatistics and Programming, Janssen Research & Development, LLC, Horsham, Pennsylvania, USA.
Jianping
J
Wang
Biostatistics and Programming, Janssen Research & Development, LLC, Horsham, Pennsylvania, USA.
Kezhen L
KL
Tang
Biologics Clinical Pharmacology, Janssen Research & Development, LLC, Spring House, Pennsylvania, USA.
Zhenhua
Z
Xu
Department of Gastroenterology, University Hospital Gasthuisberg, KU Leuven, Belgium.
Paul
P
Rutgeerts
Department of Gastroenterology, University Hospital Gasthuisberg, KU Leuven, Belgium National Fund for Scientific Research (FWO), Flanders, Belgium.
Séverine
S
Vermeire
D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002097:C-Reactive Protein / Q000032:analysis*; D003424:Crohn Disease / Q000188:drug therapy*; D005260:Female; D006801:Humans; D000069285:Infliximab; D008297:Male; D008875:Middle Aged; D012074:Remission Induction; D012189:Retrospective Studies; D016896:Treatment Outcome; D055815:Young Adult
D000911:Antibodies, Monoclonal; D002097:C-Reactive Protein; D000069285:Infliximab
CROHN'S DISEASE; INFLIXIMAB; PHARMACOKINETICS