Routine home monitoring of fecal calprotectin every two months did not reduce symptomatic flares in patients with ulcerative colitis (UC) in remission compared with standard care, according to a multicenter randomized trial. However, patients whose treatment was adjusted after persistently elevated fecal calprotectin levels experienced numerically fewer flares, suggesting that biomarker monitoring may be more effective when elevated results prompt a predefined treatment change.
The findings, published in Gastroenterology, address a longstanding question about whether proactive biomarker monitoring can prevent relapse before symptoms appear. Fecal calprotectin, a marker of intestinal inflammation, often rises months before a clinical flare, and current guidelines recommend periodic testing for patients with UC who are in symptomatic remission. Although elevated fecal calprotectin levels have been linked to an increased risk of relapse, it has remained unclear whether frequent home testing improves patient outcomes.
“Home-based fecal calprotectin testing strongly correlates with lab-based ELISA testing, and high rates of patient acceptance have been reported with its use,” wrote the investigators, who were led by first author Gregory Rosenfeld, MD, of the IBD Centre of BC, Vancouver, Canada. “We hypothesized that intensive, proactive home-based fecal calprotectin monitoring in patients with UC in symptomatic remission would prevent symptomatic flares and improve patient outcomes.”
For the trial, known as PROMOTE UC, researchers enrolled 716 adults with UC in symptomatic remission at 14 centers in Canada and Australia between November 2018 and December 2022. Participants were randomly assigned to standard care or home fecal calprotectin testing every two months for up to 18 months using a smartphone-based test. Patients with fecal calprotectin levels of at least 250 µg/g repeated the test within two weeks. Decisions about changing treatment were left to the treating physician. The primary endpoint was time to symptomatic flare. Secondary endpoints included hospitalizations, surgery, medication use, physician visits, quality of life, work or school absenteeism, and medication adherence.
After excluding patients lost to follow-up before receiving any intervention, the modified intention-to-treat analysis included 611 patients: 308 assigned to standard care and 303 to home monitoring. The average age was 42 years, 47% were men, and patients had lived with UC for an average of 11 years. About 45% were receiving advanced therapy at baseline. Disease extent and baseline fecal calprotectin levels were similar between the two groups.
By the end of follow-up, 32% of patients in both groups experienced a symptomatic flare, with 97 flares in the standard-care group and 96 in the home-monitoring group. Median time to flare was not reached in either group during the approximately 18-month follow-up. Flare rates were nearly identical, at about 0.29 flares per person-year, with no significant difference in the risk of flare between the two groups.
The findings were consistent across all predefined subgroup analyses. Home monitoring did not reduce flare risk in patients with proctitis, left-sided colitis, or pancolitis, or in those receiving either advanced therapies or conventional treatment. The results also did not change after excluding control patients who underwent fecal calprotectin testing outside the study protocol.
One unexpected finding emerged in a sensitivity analysis of patients' adherence to home testing. Nearly half of the patients assigned to home monitoring missed at least three scheduled tests. When investigators excluded patients after their third missed test, home monitoring was linked to a higher likelihood of symptomatic flare. The authors said this unexpected result may reflect detection bias, with more frequent testing leading patients to notice and report symptoms more often rather than indicating worse disease. A similar pattern was seen among patients whose baseline fecal calprotectin level was below 100 µg/g. In that subgroup, patients in the home-monitoring group also appeared more likely to experience a flare.
The study also examined whether patients with persistently elevated fecal calprotectin might benefit from earlier treatment changes. During follow-up, 88 patients developed confirmed elevations after initially having levels below the treatment threshold. Of those patients, 44% had their treatment changed at least two weeks before the end of the study. Symptomatic flares occurred in 49% of patients whose treatment was changed compared with 55% of those whose treatment remained the same, but the difference was not statistically significant.
None of the secondary outcomes differed between the groups. Rates of UC-related surgery and hospitalization were low and similar, as were new prescriptions for corticosteroids or advanced therapies, physician visits, medication adherence, quality-of-life scores, and missed work or school days. Patients successfully completed and transmitted 92% of home fecal calprotectin tests, although many missed multiple scheduled tests over time, highlighting the challenge of maintaining long-term adherence.
For practicing gastroenterologists, the findings suggest that routine biomarker monitoring alone may not improve outcomes if treatment decisions are left to physician discretion. Instead, the results support continued use of fecal calprotectin to assess inflammatory activity while underscoring the need for standardized treatment protocols when levels rise. "Our prospective study in patients with UC in symptomatic remission suggests that proactive monitoring without protocolized escalation utilizing home-based fecal calprotectintesting does not prevent symptomatic flares,” the authors concluded. “Additional studies with clinician- and/or patient-directed protocolized interventions are needed to define the optimal use of proactive fecal calprotectinhome monitoring and the benefit of early intervention in patients with UC.”
The investigators acknowledged several limitations. Symptomatic flares were not routinely confirmed by endoscopy, raising the possibility that some patients were misclassified. Treatment changes after elevated fecal calprotectin results were left to the treating physician rather than guided by a study protocol, making it difficult to assess the value of early intervention. Nearly half of patients in the home-monitoring group missed three or more scheduled tests, reducing the study's statistical power, and about 15% of enrolled patients were lost to follow-up before receiving the intervention. The trial also took place during the COVID-19 pandemic, which made patient retention and follow-up more difficult.
The study was funded by the Canadian Inflammatory Bowel Disease Research Consortium, Crohn's and Colitis Canada, Ferring, and Pfizer, with in-kind donations from AbbVie and Bühlmann. Dr. Rosenfeld and several coauthors reported research funding, consulting fees, speaker honoraria, or advisory relationships with pharmaceutical companies involved in IBD care.