Highlight
- Proactive fecal calprotectin (FC) home monitoring every 2 months did not reduce risk or delay time to symptomatic ulcerative colitis (UC) flare compared to standard care.
- No differences were seen in secondary outcomes including healthcare utilization, medication use, or quality of life.
- Among patients who escalated therapy after confirmed high FC, flare frequency was numerically lower but without statistically significant risk reduction.
- The study suggests that home FC monitoring alone, without a strict escalation protocol, may not prevent UC flares, indicating a need for further research on optimal use and intervention strategies.
Background
Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by episodic relapses that substantially impair quality of life and impose healthcare burdens. Early detection of intestinal inflammation preceding symptomatic flares is conceptually appealing to guide timely therapeutic escalation to prevent clinical deterioration. Fecal calprotectin (FC) is a well-established noninvasive biomarker reflecting neutrophil-driven intestinal inflammation, rising several months before symptom onset in UC patients. Despite its diagnostic and prognostic utility in clinical settings, the value of routine, proactive home-based FC monitoring in guiding preemptive treatment adjustments to avert flares remains unclear. This multicenter randomized controlled trial (RCT) evaluated whether bi-monthly home FC monitoring reduces the incidence or delays the timing of symptomatic flares in UC patients in remission compared with standard clinical care.
Study Design
This prospective, multicenter RCT randomized adult patients with UC in clinical remission, defined by a modified partial Mayo score ≤2 and absence of rectal bleeding, to either standard care or an intervention involving fecal calprotectin testing at home every 2 months for up to 18 months or until symptomatic flare. Elevated FC levels (≥250 µg/g) prompted confirmatory retesting within 2 weeks, after which therapeutic changes were at the treating physician’s discretion without a mandated protocol. The primary endpoint was time to symptomatic flare, operationalized as clinical worsening necessitating escalation of medical therapy. Secondary endpoints encompassed measures of healthcare utilization, medication adjustments, and patient-reported quality of life.
Results
A total of 716 patients were enrolled, with 308 analyzed in the control arm and 303 in the intervention arm. Baseline characteristics were balanced; mean age was 42 years, 47% were male, disease extent and advanced therapy use (45%) were comparable between groups.
During the study, 32% of patients in both arms experienced symptomatic flares, with the median time to flare not reached in either group. There was no significant difference in the risk of flare between the intervention and control arms (hazard ratio 1.05, 95% confidence interval 0.79 to 1.40), irrespective of disease extent or advanced therapy status. Among the subset of 88 patients who modified therapy after confirming elevated FC, the frequency of flares was modestly lower (49% vs. 55% in those who did not escalate), but this did not translate into a statistically significant difference in flare risk.
Secondary endpoints including healthcare utilization metrics, medication use patterns, and quality of life assessments revealed no significant differences between groups. Importantly, the intervention was well-tolerated with no reported safety concerns related to home FC monitoring or ensuing decisions.
Expert Commentary
This landmark RCT provides important clinical insight into the pragmatic utility of proactive home FC monitoring in UC management. Although the biomarker reliably anticipates mucosal inflammation, this study reveals that its routine home application without a structured treatment escalation algorithm does not reduce symptomatic flares or improve patient outcomes. Prior observational studies and expert consensus have supported FC measurement to guide management; however, the absence of a prespecified intervention protocol in this trial may have contributed to the neutral findings. The discretionary nature of therapy adjustments likely introduced variability in clinical responses.
Furthermore, the modest reduction in flare frequency among patients who escalated therapy suggests a potential biological signal that supports early intervention following biomarker elevation. This underscores an unmet need to define evidence-based thresholds and standardized treatment pathways linked to FC results to maximize clinical benefit.
Limitations include reliance on patient adherence to home testing schedules and physician discretion, which may limit generalizability. Additionally, incorporation of endoscopic or histologic endpoints could provide a more comprehensive disease activity assessment in future studies.
Conclusion
This well-powered RCT demonstrates that proactive home monitoring of fecal calprotectin every two months in patients with quiescent ulcerative colitis does not prevent symptomatic flares when therapy escalation is not protocol-driven. While the concept of biomarker-driven preemptive treatment is compelling, implementing such strategies in routine clinical practice requires standardized protocols integrating FC results with timely therapeutic modifications. Additional investigations are warranted to optimize biomarker-guided management algorithms, establish thresholds for intervention, and evaluate their impact on long-term disease trajectory and healthcare utilization in UC.
Funding and Trial Registration
The trial was registered under ClinicalTrials.gov number NCT03549988. Funding sources were not specified in the summary but may be detailed in the full publication.
References
Rosenfeld G, Narula N, Leung Y, et al. Proactive Fecal Calprotectin Home Monitoring in Ulcerative Colitis: Results of a Prospective Randomized Control Trial. Gastroenterology. 2026 Jun 23. PMID: 42336164. https://pubmed.ncbi.nlm.nih.gov/42336164/
Additional references on fecal calprotectin utility and biomarker-guided strategies in UC can be consulted for deeper context.