Surrogate markers and clinical indices, alone or combined, as indicators for endoscopic remission in anti-TNF-treated luminal Crohn's disease

Abstract

Objective. Endoscopically confirmed mucosal healing has become an important therapeutic goal in the treatment of Crohn's disease (CD). The role of clinical indices, such as the Crohn's disease activity index (CDAI) and the Harvey–Bradshaw index (HBI), and surrogate markers, such as C-reactive protein (CRP) and fecal calprotectin, to indicate remission determined by endoscopy needs to be clarified. We analyzed the role of surrogate markers and clinical indices, separately and in combination, by comparing them with endoscopically scored disease activity in biologically treated CD patients. Material and methods. Prospectively collected data of all patients with inflammatory bowel disease treated with tumor necrosis factor alpha antibodies in a tertiary center between 2007 and 2010. Altogether 210 endoscopies in 64 CD patients were analyzed. The simple endoscopic score for Crohn's disease (SES-CD) was used for scoring disease activity and compared with available data on concurrent CDAI, HBI, CRP, and calprotectin. Results. Endoscopic activity demonstrated a stronger correlation with calprotectin and CRP than with the clinical indices. Neither the clinical indices nor CRP was reliable at identifying endoscopic remission. However, calprotectin alone identified endoscopic remission with a sensitivity of 84% and specificity of 74%, but was beaten, although not statistically significantly, by a combined index, based on calprotectin and the HBI. Conclusions. Clinical scores commonly used in the assessment of disease activity are unreliable at differentiating endoscopic remission from active CD. Despite this, a score based on a combination of fecal calprotectin and the HBI is a new promising tool for identifying endoscopic remission.

Key Words::

• adalimumab
• calprotectin
• CDAI
• combined activity index
• Crohn's disease
• Harvey–Bradshaw index
• infliximab
• SES-CD

Acknowledgements

We thank study nurse Pirkko Tuukkala for technical assistance. The study was supported by unrestricted grants from the Medical Society of Finland, the Finnish Foundation for Gastroenterological Research, and MSD Finland. Statement of authorship: CGB designed the study, carried out the studies and data analyses, performed the statistical analyses, and drafted and finished the manuscript. UN designed the study, carried out the studies, assisted in the statistical analyses, and helped to draft the manuscript. UT participated in the design of the study, carried out the studies, and helped to draft the manuscript. PA participated in the design of the study, carried out the studies, and helped to draft the manuscript. TS participated in the design of the study, carried out the studies, and helped to draft the manuscript. MF designed and supervised the study, carried out the studies, and helped to draft the manuscript. All authors read and approved the final manuscript.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.