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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.

ABSTRACT: Serum infliximab trough levels correlate with efficacy; dose escalation is often beneficial in patients with Crohn's disease who stop responding to infliximab treatment.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).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.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??g/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.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.

SUBMITTER: Cornillie F

PROVIDER: S-EPMC4215276 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

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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.

Cornillie Freddy F Hanauer Stephen B SB Diamond Robert H RH Wang Jianping J Tang Kezhen L KL Xu Zhenhua Z Rutgeerts Paul P Vermeire Séverine S

Gut 20140128 11

<h4>Background</h4>Serum infliximab trough levels correlate with efficacy; dose escalation is often beneficial in patients with Crohn's disease who stop responding to infliximab treatment.<h4>Objective</h4>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 sustai ...[more]

PMID: 24474383

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Project description:BACKGROUND AND AIMS:Recent adult evidence suggests that infliximab (IFX) trough levels (TL) in patients with severe ulcerative colitis (UC) may be decreased. The aims of our study were to compare post-induction IFX TL of children with severe versus moderate UC and to evaluate short- and long-term outcomes. METHODS:In this single-center retrospective study, children with a diagnosis of UC starting IFX with a Pediatric Ulcerative Colitis Activity Index (PUCAI) ?35 and with available post-induction TL were recruited. UC characteristics, IFX dosage and interval, primary non-response, IFX failure, and surgery after 24 months were collected. Post induction TL, anti-IFX antibodies, and laboratory evaluations at the time of starting IFX were also acquired. RESULTS:A total of 90 children were enrolled, of whom 39 (43.3%) were classified as severe UC and 51 (56.6%) as moderate UC. Median post-induction IFX TL were lower in severe UC versus moderate group (5.5 vs 10.3; p?=?0.03), despite a more frequently intensified IFX regimen. Children in the higher TL quartiles showed increased rates of clinical, biological, and combined remission (p?=?0.04, p?<?0.001, and p?=?0.01, respectively). In a multivariate analysis, a PUCAI ?65 and time interval from last IFX infusion were the only predictors associated with IFX TL. At 24 months, children in the higher TL quartiles had a decreased risk of IFX failure (p?=?0.002). The severe UC group showed a higher risk of IFX failure at 24 months (16/23 (41%) vs. 11/40 (21.6%); p?=?0.05). Kaplan-Meier methods demonstrated a trend toward statistical significance, with a two-year cumulative colectomy rate of 15.38% (95% confidence interval (CI) 8.1-15.6%) in children with severe UC and 3.92% (95% CI 2.9-10.8%) in patients with moderate UC (logrank test p?=?0.06). CONCLUSIONS:Children starting IFX with severe UC showed lower post-induction TL and poor disease outcomes. Achieving adequate TL was associated with better efficacy outcomes.

Dataset Information

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.

Publications

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.

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