Defining the ultrasound longitudinal natural history of newly diagnosed pediatric small bowel Crohn disease treated with infliximab and infliximab-azathioprine combination therapy

Little is known about changes in the imaging appearances of the bowel and mesentery over time in either pediatric or adult patients with newly diagnosed small bowel Crohn disease treated with anti-tumor necrosis factor-alpha (anti-TNF-alpha) therapy. To define how bowel ultrasound findings change over time and correlate with laboratory inflammatory markers in children who have been newly diagnosed with pediatric small bowel Crohn disease and treated with infliximab. We included 28 pediatric patients treated with infliximab for newly diagnosed ileal Crohn disease who underwent bowel sonography prior to medical therapy and at approximately 2 weeks, 1 month, 3 months and 6 months after treatment initiation; these patients also had laboratory testing at baseline, 1 month and 6 months. We used linear mixed models to compare mean results between visits and evaluate whether ultrasound measurements changed over time. We used Spearman rank correlation to assess bivariate relationships. Mean subject age was 15.3 +/- 2.2 years; 11 subjects were girls (39%). We observed decreases in mean length of disease involvement (12.0 +/- 5.4 vs. 9.1 +/- 5.3 cm, P=0.02), maximum bowel wall thickness (5.6 +/- 1.8 vs. 4.7 +/- 1.7 mm, P=0.02), bowel wall color Doppler signal (1.7 +/- 0.9 vs. 1.2 +/- 0.8, P=0.002) and mesenteric color Doppler signal (1.1 +/- 0.9 vs. 0.6 +/- 0.6, P=0.005) at approximately 2 weeks following the initiation of infliximab compared to baseline. All laboratory inflammatory markers decreased at 1 month (P-values < 0.0001). There was strong correlation between bowel wall color Doppler signal and fecal calprotectin (rho=0.710; P < 0.0001). Linear mixed models confirmed that maximum bowel wall thickness (P=0.04), length of disease involvement (P=0.0002) and bowel wall color Doppler signal (P < 0.0001) change over time in response to infliximab, when adjusted for age, sex, azathioprine therapy, scanning radiologist and baseline short pediatric Crohn's disease activity index score. The ultrasound appearance of the bowel changes as early as 2 weeks after the initiation of infliximab therapy. There is strong correlation between bowel wall color Doppler signal and fecal calprotectin.