Changes of fecal calprotectin concentrations after adalimumab induction therapy in patients with moderate-to-severe Crohn's disease

Abstract

Background: In the era of biologics, mucosal healing (MH) has been proposed as a treatment goal for Crohn's disease (CD) because of its association with favorable long-term disease outcomes. Fecal calprotectin (FC), a neutrophil-derived protein, is a sensitive marker of intestinal inflammation and correlates closely with endoscopic disease activity. We examined the changes of FC concentrations in patients with moderate to severe CD receiving adalimumab induction therapy. Methods: This was a prospective, multicenter, observational study. Moderately to severely active luminal CD patients with baseline FC≥150 μg/g were treated with adalimumab and followed up every 4 weeks for 12 weeks. Crohn's disease activity index (CDAI) and fecal calprotectin were measured at baseline, 4, 8, and 12 weeks. Fecal samples for calprotectin were shipped to central laboratory for a quantitative analysis using ELISA. Primary endpoint was the percentage of patients with FC concentration< 150 μg/g after completion of adalimumab induction treatment at week 4. Results: A total of 93 patients were enrolled in this study. Patients showed male predominance (M:F=2.1:1) and mean age was 30.7 ± 8.9 years. CDAI score decreased from 288.2 ± 60.2 at baseline to 129.9 ± 74.9 at week 4, and 66% of patients achieved clinical remission (CDAI <150) at that time point. Accordingly, FC concentration fell from 1799.6 ± 2275.3 μg/g at baseline to 854.4 ± 1002.1 μg/g at week 4 (percent change -34.6 ± 59.9, P<0.0001). However, only 16% of patients showed FC<150 μg/g at week 4. The proportions were increased up to 21.9% and 18.8% at 8 and 12 week, respectively. Conclusions: FC concentrations are significantly decreased with adalimumab treatment, implicating improvement of intestinal inflammation. However, FC remained high level in considerable patients with symptomatic improvement. Long-term follow up study is needed to explore the clinical significance of subclinical inflammation in adalimumab-treated CD.