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Infliximab Maintains Durable Response and Facilitates Catch-up Growth in Luminal Pediatric Crohn's Disease

Church, Peter C. MD*; Guan, Jack BSc*; Walters, Thomas D. MSc, MD*,†; Frost, Karen MN*,†; Assa, Amit MD*; Muise, Aleixo M. MD, PhD*,†,‡; Griffiths, Anne M. MD*,†

Inflammatory Bowel Diseases:
doi: 10.1097/MIB.0000000000000083
Original Clinical Articles
Abstract

Background: Infliximab induces and maintains clinical remission in children with Crohn's disease (CD), but specifically pediatric long-term data remain sparse.

Methods: Patients (N = 195) who received infliximab ± immunomodulator for luminal CD were retrospectively reviewed. Outcomes included clinical response, linear growth, and mucosal healing. Durability of response was assessed using Cox proportional hazards models. Levels of infliximab and antibodies (antibodies to infliximab) were measured when response was lost.

Results: Among 195 patients (median age, 13.9 yr; median CD duration, 1.6 yr), 81% experienced complete response (judged by physician global assessment and pediatric Crohn's disease activity index ≤10). Longer duration of diagnosed CD and female gender were associated with lower response. During first year of follow-up, 35% of subjects had regimen individualized through dose escalation/interval shortening. Despite regimen optimization, 16/157 complete responders experienced loss of response at a rate of 2% to 6% per year over 5 years, associated with development of antibodies to infliximab. Concurrent immunomodulation for ≥30 weeks significantly decreased loss of response (hazard ratio = 0.25, 95% confidence interval, 0.08–0.76; P = 0.014). Follow-up endoscopic examination was performed in 40 responders, of whom 22 (73%) demonstrated complete resolution of mucosal ulceration. Patients with growth potential (Tanner 1/2 at induction) demonstrated significant improvements in mean height z-score from induction to years 1 and 2 of follow-up (P < 0.001). With infliximab initiation within the first 18 months after diagnosis, mean height z-score normalized to 0 after 3 years.

Conclusions: These data demonstrate sustained effectiveness of infliximab in children and adolescents with luminal CD. Durability of response is increased by concomitant immunomodulation. Clinical response is associated with enhanced linear growth, particularly when therapy is initiated early.

In Brief

Article first published online 23 May 2014.

Author Information

*Division of Gastroenterology, Hepatology and Nutrition, Department of Paediatrics, University of Toronto, Toronto, ON, Canada;

SickKids Inflammatory Bowel Disease Center, The Hospital for Sick Children, Toronto, ON, Canada; and

Cell Biology Program, Research Institute and the Institute of Medical Science, University of Toronto, Toronto, ON, Canada.

Reprints: Anne M. Griffiths, MD, The Hospital for Sick Children, 555 University Avenue, Toronto, ON M4S 1C5, Canada (e-mail: anne.griffiths@sickkids.ca).

Data extraction was supported by an investigator-initiated grant from Janssen Canada.

P. C. Church has received salary support through a Janssen Canada IBD fellowship. T. D. Walters has received consultant and speaker fees from Janssen Canada. K. Frost has received speaker fees from Janssen Canada. A. M. Griffiths has received consultant and speaker fees from Janssen Canada. The other authors have no conflicts of interest to disclose.

Received February 20, 2014

Accepted April 18, 2014

© Crohn's & Colitis Foundation of America, Inc.

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