Standardizing Fecal Calprotectin Monitoring in Asymptomatic Patients with Inflammatory Bowel Disease

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To the Editor:
We would like to thank Dr. Cong Dai et al for their interest in our manuscript1 and raising the question of intraindividual calprotectin variability.2 Our systematic review, including results of electronic searches up to April 21, 2016, found a limited number of prospective studies that monitored asymptomatic patients by repeating calprotectin measurements. Our evaluation of the literature also underscored the practicality of repeating calprotectin across standardized time intervals to inform clinical decision making. Although the heterogeneity of the included studies in our analysis precluded the identification of an optimal cutoff, this does not reduce the utility of the “take-home” message we sought to convey: monitoring requires repeating calprotectin within 1 to 3 months apart.
Although the studies that Dr. Dai et al cite as having discrepancy in cutoffs reiterate the current knowledge gap, we highlight that these studies either had only a single follow-up calprotectin measurement3,4 or nonstandardized (>3-month interval) follow-up calprotectin measurements.4–6 Therefore, the heterogeneity of the study design in the aforementioned studies—not the intraindividual calprotectin variability—does not allow for reliable comparison of reported cutoff levels. Apart from that, we suspect a possible overlap of 2 patient cohorts described by 1 research group.6,7 The second article of this group was published after our data cut but would otherwise have been included in our search.7 The findings of this study underline our conclusion that calprotectin can function as prelude for relapse.
Finally, it is important to note that standardizing calprotectin monitoring should not only consider patient education to obtain the first-morning stool to minimize the intraindividual variability but also consider standardizing the length of time between sampling and processing of the sample in the laboratory.2 In addition, inherent differences between assays and phenotypic disease differences (e.g., colonic-only versus ileal-only involvement) between individuals are important considerations for increased variability. The essence of the practical guide in our review is that the clinician could detect an imminent relapse in asymptomatic patients when calprotectin levels are monitored every 2 to 3 months.

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