Beyond mucosal healing: fecal calprotectin and the path toward histologic remission in ulcerative colitis

Yehyun Park

doi:10.5217/ir.2025.00056

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Editorial IBD Beyond mucosal healing: fecal calprotectin and the path toward histologic remission in ulcerative colitis: Yehyun Park^,; Intestinal Research 2025;23(2):115-116.
DOI: https://doi.org/10.5217/ir.2025.00056
Published online: April 29, 2025

Department of Internal Medicine, Ewha Womans University Seoul Hospital, Seoul, Korea

Correspondence to Yehyun Park, Department of Internal Medicine, Ewha Womans University Seoul Hospital, Ewha Womans University College of Medicine260 Gonghang-daero, Gangseo-gu, Seoul 07804, Korea. E-mail: splendidyh1029@gmail.com

• Received: April 13, 2025 • Accepted: April 20, 2025

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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REFERENCES

See the article "Predictive accuracy of fecal calprotectin for histologic remission in ulcerative colitis" on page 144.

Ulcerative colitis (UC) management has evolved with increasing emphasis on achieving not only symptomatic control but also endoscopic remission, which is currently recognized as a formal therapeutic target [1]. According to the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE)-II recommendations, treatment targets in UC should be viewed as a continuum encompassing short-term (symptomatic response/remission), intermediate (normalization of inflammatory biomarkers such as C-reactive protein and fecal calprotectin [FC]), and long-term goals (endoscopic healing and restoration of quality of life) [1]. Although histologic healing is not yet established as a routine clinical endpoint, it is increasingly regarded as an important target due to its association with reduced relapse rates, lower corticosteroid use, and fewer long-term complications [2,3]. While there are no randomized controlled trials specifically evaluating treat-to-target strategies in UC, indirect evidence from Crohn’s disease—notably the CALM study—demonstrates that a tight control strategy incorporating both symptoms and biomarkers is more effective than symptom-driven care alone in achieving deep remission. This, in turn, leads to a lower risk of complications, surgery, and hospitalization [4]. However, the degree of correlation among clinical symptoms, biomarkers, and endoscopic healing remains uncertain. Also, in routine clinical practice, repeated endoscopic assessments are invasive, costly, and may be impractical. Therefore, there is an important need to determine whether noninvasive biomarkers can serve as accurate and reliable surrogates for mucosal inflammation, and be suitable for implementation in UC care pathways [5].

Among noninvasive biomarkers, FC has demonstrated reasonable utility in predicting mucosal healing, especially at levels below 150 µg/g [6]. However, the optimal cutoff for predicting histologic remission remains undefined. Furthermore, among the various histologic indices used in UC—such as the Geboes Score (GS), Nancy Index (NI), and Robarts Histopathology Index (RHI)—it is not yet clear which best correlates with clinical symptoms, endoscopic findings, or biomarkers [3,7].

In the current issue of Intestinal Research, Singh et al. [8] evaluated the predictive performance of FC for histologic remission in a prospective cohort of 347 patients with UC. The authors compared four histologic scoring systems—GS, continuous GS, NI, and RHI—and found high concordance among them. Importantly, they demonstrated that FC levels below 100 µg/g predicted histologic remission with ≥ 85% accuracy across all indices. This study provides robust evidence supporting the role of FC as a surrogate marker for histologic remission, particularly when applying stringent thresholds. The strength of correlation between FC and histologic indices was stronger than that with clinical or endoscopic measures, echoing findings from prior meta-analyses [9]. Notably, the data also suggest that histologic remission may precede endoscopic healing, challenging the traditional concept of mucosal healing hierarchy and underscoring the need for further longitudinal validation [10].

By validating FC thresholds against multiple histologic indices, this study strengthens the role of FC as a key component of treat-to-target strategies in UC [1], particularly by supporting its use as a surrogate marker for histologic remission. Such an approach may reduce the need for frequent invasive assessments and help advance a more patient-centered, efficient UC management paradigm. While the single-center design and the lack of longitudinal follow-up are limitations, the clinical implications are compelling. Future studies should aim to validate these findings in multicenter, longitudinal cohorts and evaluate their relevance in predicting long-term outcomes such as relapse, hospitalization, and colectomy [9].

NOTES

Funding Source

The author received no financial support for the research, authorship, and/or publication of this article.

Conflict of Interest

No potential conflict of interest relevant to this article was reported.

Data Availability Statement

Not applicable.

Author Contributions

Writing and approval of the final manuscript: Park Y.

REFERENCES

1. Turner D, Ricciuto A, Lewis A, et al. STRIDE-II: an update on the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) Initiative of the International Organization for the Study of IBD (IOIBD): determining therapeutic goals for Treat-to-Target strategies in IBD. Gastroenterology 2021;160:1570–1583.Article PubMed
2. Pai RK, D’Haens G, Kobayashi T, et al. Histologic assessments in ulcerative colitis: the evidence behind a new endpoint in clinical trials. Expert Rev Gastroenterol Hepatol 2024;18:73–87.Article PubMed
3. Wang H, Fewings I, Bornman L, Shadbolt B, Fadia M, Subramaniam K. Histologic remission (NANCY Index) is superior to endoscopic mucosal healing in predicting relapse free survival in patients with ulcerative colitis in clinical and endoscopic remission. J Clin Gastroenterol 2023;57:494–500.Article PubMed
4. Colombel JF, Panaccione R, Bossuyt P, et al. Effect of tight control management on Crohn’s disease (CALM): a multicentre, randomised, controlled phase 3 trial. Lancet 2017;390:2779–2789.Article PubMed
5. Magro F, Lopes J, Borralho P, et al. Comparison of different histological indexes in the assessment of UC activity and their accuracy regarding endoscopic outcomes and faecal calprotectin levels. Gut 2019;68:594–603.Article PubMed
6. Singh S, Ananthakrishnan AN, Nguyen NH, et al. AGA Clinical Practice Guideline on the role of biomarkers for the management of ulcerative colitis. Gastroenterology 2023;164:344–372.Article PubMed
7. Akiyama S, Miyatani Y, Rubin DT. The evolving understanding of histology as an endpoint in ulcerative colitis. Intest Res 2024;22:389–396.Article PubMed PMC PDF
8. Singh A, Bhardwaj A, Sharma R, et al. Predictive accuracy of fecal calprotectin for histologic remission in ulcerative colitis. Intest Res 2025;23:144–156.Article PubMed PDF
9. Ye X, Wang Y, Wang HHX, et al. Can fecal calprotectin accurately identify histological activity of ulcerative colitis? A meta-analysis. Therap Adv Gastroenterol 2021;14:1756284821994741.Article PubMed PMC PDF
10. Rath T, Atreya R, Bodenschatz J, et al. Intestinal barrier healing is superior to endoscopic and histologic remission for predicting major adverse outcomes in inflammatory bowel disease: the prospective ERIca Trial. Gastroenterology 2023;164:241–255.Article PubMed

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Beyond mucosal healing: fecal calprotectin and the path toward histologic remission in ulcerative colitis

Intest Res. 2025;23(2):115-116. Published online April 29, 2025

DOI: https://doi.org/10.5217/ir.2025.00056

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Beyond mucosal healing: fecal calprotectin and the path toward histologic remission in ulcerative colitis