Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Multicenter Study
. 2023 Aug 1;14(8):e00605.
doi: 10.14309/ctg.0000000000000605.

Fecal Biomarkers of Neutrophil and Eosinophil Origin Reflect the Response to Biological Therapy and Corticosteroids in Patients With Inflammatory Bowel Disease

Maria Ling Lundström  1 , Christer Peterson  2 , Maria Lampinen  1 , Charlotte R H Hedin  3   4 , Åsa V Keita  5 , Robert Kruse  6 , Maria K Magnusson  7 , Carl Mårten Lindqvist  8 , Dirk Repsilber  8 , Mauro D'Amato  9   10   11   12 , Henrik Hjortswang  13 , Hans Strid  14 , Anders Rönnblom  15 , Johan D Söderholm  5   16 , Lena Öhman  7 , Per Venge  2 , Jonas Halfvarson  17 , Marie Carlson  1 ; BIOIBD consortium
Affiliations
Multicenter Study

Fecal Biomarkers of Neutrophil and Eosinophil Origin Reflect the Response to Biological Therapy and Corticosteroids in Patients With Inflammatory Bowel Disease

Maria Ling Lundström et al. Clin Transl Gastroenterol. .

Abstract

Introduction: Fecal calprotectin (FC) is a noninvasive tool for examining response to biologics in inflammatory bowel disease (IBD), but its performance in relation to other novel fecal markers of various cellular origins is unknown.

Methods: We performed a prospective multicenter cohort study and included patients with active IBD who provided a fecal sample at initiation of biological therapy. Levels of FC, myeloperoxidase (MPO), human neutrophil lipocalin (HNL), and eosinophil-derived neurotoxin (EDN) were analyzed and related to clinical remission status at 3 months. Changes in levels of markers at 3 months were calculated, and the impact of concomitant use of corticosteroids at baseline was estimated.

Results: In patients achieving clinical remission (n = 27), a decrease in levels of FC ( P = 0.005), MPO ( P < 0.001), HNL ( P < 0.001), and EDN ( P < 0.001) was observed, whereas no significant decrease was seen in patients not achieving remission (n = 39). There was a significant difference in the change in the level of MPO ( P = 0.01) and HNL ( P = 0.02) between patients achieving clinical remission and those who did not, but changes in FC and EDN could not differentiate between these groups. Patients with concomitant systemic corticosteroids at inclusion had lower levels of HNL ( P = 0.01) and EDN ( P < 0.001) at baseline, compared with patients without corticosteroids.

Discussion: Fecal MPO, HNL, and EDN are all promising biomarkers for assessing the treatment outcome of biologics in patients with IBD. Fecal levels of EDN and HNL are significantly affected by corticosteroids indicating a greater sensitivity to the effects of corticosteroids compared with levels of FC and MPO.

PubMed Disclaimer

Conflict of interest statement

Guarantor of the article: Marie Carlson, MD, PhD.

Specific author contributions: J.H. and M.C.: study concept and design. M.L.L., C.R.H.H., H.H., H.S., A.R., J.H., and M.C.: patient recruitment. M.L.L., R.K. and C.P.: sample processing and sample analysis. M.L.L., C.P., P.V., J.H.: and M.C.: data analysis and interpretation. M.L.L., M.L., J.H., and M.C.: drafting the manuscript. J.H., C.R.H.H., Å.V.K., R.K., M.K.M., C.M.L., D.R., M.D.A., J.D.S., L.Ö. and M.C.: study coordination. All authors were involved in critical review, editing, revision, and approval of the final manuscript submission.

Financial support: This work was supported by the Swedish Foundation for Strategic Research (grant number RB13-016), Medical Faculty, Uppsala University, Uppsala, Sweden (M.C.) and the Örebro University Hospital Research Foundation (grant numbers OLL-936004, OLL-890291, OLL-790011, OLL-723021, and OLL-333321 to J.H.).

Potential competing interests: H.S. served as a speaker and/or advisory board member for AbbVie, Galapagos, Janssen, Takeda, and Pfizer. J.H. served as a speaker and/or advisory board member for AbbVie, BMS, Celgene, Celltrion, Dr. Falk Pharma and the Falk Foundation, Ferring, Galapagos, Gilead, Hospira, Index Pharma, Janssen, MEDA, Medivir, MSD, Novartis, Pfizer, Prometheus Laboratories Inc., Sandoz, Shire, Takeda, Thermo Fisher Scientific, Tillotts Pharma, Vifor Pharma, and UCB and received grant support from Janssen, MSD, and Takeda. The remaining authors declare no competing interests.

IRB approval statement: This study was approved by the Regional Ethics Review Board, Uppsala, Sweden (2010/313/2), on March 16, 2015. All patients received verbal and written information and gave their written informed consent before participation.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Study flow chart.
Figure 2.
Figure 2.
Marker-level changes for FC, MPO, HNL, and EDN between baseline and 3 months for patients with IBD (CD, n = 39 and UC, n = 27) initiating biological therapy with anti-TNF, vedolizumab, or ustekinumab. Changes in levels of markers are reported separately for patients achieving clinical remission (n = 27) and patients not achieving clinical remission (n = 39). For the comparison of differences within groups, a Wilcoxon signed rank test was used. CD, Crohn's disease; EDN, eosinophil-derived neurotoxin; FC, fecal calprotectin; HNL, human neutrophil lipocalin; MPO, myeloperoxidase; TNF, tumor necrosis factor; UC, ulcerative colitis.
Figure 3.
Figure 3.
Changes in the levels of FC, MPO, HNL, and EDN between baseline and 3 months in patients achieving clinical remission (n = 27) and patients not achieving clinical remission (n = 39) at 3 months. Patients studied had either CD or UC and initiated therapy with anti-TNF, vedolizumab, or ustekinumab at baseline. For comparison of differences in level changes between groups, a Mann-Whitney test was used. CD, Crohn's disease; EDN, eosinophil-derived neurotoxin; FC, fecal calprotectin; HNL, human neutrophil lipocalin; MPO, myeloperoxidase; TNF, tumor necrosis factor; UC, ulcerative colitis.
Figure 4.
Figure 4.
Biomarker levels at baseline for FC, MPO, HNL, and EDN in 99 patients with IBD (CD, n = 57, UC, n = 41, and IBD-U, n = 1) with (n = 43) or without (n = 56) ongoing systemic corticosteroid treatment. For comparison of groups, a Mann-Whitney test was used. CD, Crohn's disease; EDN, eosinophil-derived neurotoxin; FC, fecal calprotectin; HNL, human neutrophil lipocalin; IBD, inflammatory bowel disease; MPO, myeloperoxidase; UC, ulcerative colitis.
See this image and copyright information in PMC

References

    1. Nguyen NH, Singh S, Sandborn WJ. Positioning therapies in the management of Crohn's disease. Clin Gastroenterol Hepatol 2020;18(6):1268–79. - PMC - PubMed
    1. Danese S, Fiorino G, Peyrin-Biroulet L. Positioning therapies in ulcerative colitis. Clin Gastroenterol Hepatol 2020;18(6):1280–90.e1. - PubMed
    1. Ben-Horin S, Kopylov U, Chowers Y. Optimizing anti-TNF treatments in inflammatory bowel disease. Autoimmun Rev 2014;13(1):24–30. - PubMed
    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(5):1570–83. - PubMed
    1. Buisson A, Gonzalez F, Poullenot F, et al. Comparative acceptability and perceived clinical utility of monitoring tools: A nationwide survey of patients with inflammatory bowel disease. Inflamm Bowel Dis 2017;23(8):1425–33. - PubMed

Publication types