Associations between redox-related biomarkers and treatment response in patients with inflammatory bowel disease initiating infliximab or vedolizumab
4 affiliations
- 1Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen
- 2Department of Gastroenterology and Hepatology, Leiden University Medical Center
- 3Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen
- 4The Dr. Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai
Abstract
Background: Oxidative stress is increasingly recognized as a key component of inflammatory bowel disease (IBD) pathophysiology, yet the clinical relevance of systemic redox biomarkers during biologic therapy remains poorly understood. In this exploratory study, we investigated whether systemic redox biomarkers are associated with short-term and long-term response to infliximab (IFX) or vedolizumab (VEDO) and their relationship with iron metabolism.
Materials and Methods: Patients with active IBD initiating induction therapy with IFX or VEDO were included. Serum redox biomarkers (cysteine, homocysteine, free thiols (FTs), glutathione, and thioredoxin-1), inflammatory markers, and iron parameters were measured at baseline and during induction therapy. Patients were stratified according to short-term clinical response at week 14 and long-term response at 1 year. Longitudinal mixed-effects models, correlation analyses, and logistic regression were used to evaluate associations between redox biomarkers, treatment outcomes, and iron metabolism.
Results: Fifty-eight patients were included (IFX: n = 37; VEDO: n = 21). Induction therapy resulted in marked reductions in inflammatory markers in short-term responders. Redox biomarkers showed more modest, mostly non-significant, response-dependent patterns. IFX-treated short-term non-responders exhibited non-significant lower cysteine levels than responders at baseline (2,336 vs. 3,611 μg/mL; p > 0.05) and week 14 (2,888 vs. 3,599 μg/mL; p > 0.05). Similarly, homocysteine levels were higher in IFX-treated short-term non-responders at baseline (7,500 vs. 4,260 ng/mL; p < 0.05) and week 14 (7,002 vs. 4,278 ng/mL; p > 0.05), whereas VEDO-treated patients showed comparable levels between response groups. FT levels showed no significant changes, increasing in short-term responders while decreasing in short-term non-responders across both therapies. Glutathione levels showed no major overall changes, although levels between IFX-treated long-term responders and non-responders appeared to differ during induction therapy. Glutathione correlated inversely with transferrin saturation (r = −0.50, p < 0.05) and serum iron (r = −0.46, p < 0.05) after induction therapy.
Conclusion: Exploratory analyses suggested treatment response-related differences in cysteine, homocysteine, and FTs in IFX-treated patients, highlighting their potential as biomarkers of treatment response that warrant further investigation. Glutathione demonstrated an association with iron metabolism, suggesting a different biological role. These findings suggest a potential role for redox-iron interactions in treatment response biology that warrant further exploration and validation in larger prospective cohorts.
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BibTeX
@article{geertsema2026associations,
title = {{Associations between redox-related biomarkers and treatment response in patients with inflammatory bowel disease initiating infliximab or vedolizumab}},
author = {Sem Geertsema and Roberta Loveikyte and Sofie de Jong and Marian L. C. Bulthuis and Marjan Reinders-Luinge and Harry van Goor and Klaas Nico Faber and Arno R. Bourgonje and Gerard Dijkstra},
journal = {Frontiers in Pharmacology},
year = {2026},
month = oct,
doi = {10.3389/fphar.2026.1908844},
url = {https://www.frontiersin.org/articles/10.3389/fphar.2026.1908844/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Associations between redox-related biomarkers and treatment response in patients with inflammatory bowel disease initiating infliximab or vedolizumab
AU - Sem Geertsema
AU - Roberta Loveikyte
AU - Sofie de Jong
AU - Marian L. C. Bulthuis
AU - Marjan Reinders-Luinge
AU - Harry van Goor
AU - Klaas Nico Faber
AU - Arno R. Bourgonje
AU - Gerard Dijkstra
PY - 2026
DA - 2026/10/14
JO - Frontiers in Pharmacology
DO - 10.3389/fphar.2026.1908844
UR - https://www.frontiersin.org/articles/10.3389/fphar.2026.1908844/full
AB - Background: Oxidative stress is increasingly recognized as a key component of inflammatory bowel disease (IBD) pathophysiology, yet the clinical relevance of systemic redox biomarkers during biologic therapy remains poorly understood. In this exploratory study, we investigated whether systemic redox biomarkers are associated with short-term and long-term response to infliximab (IFX) or vedolizumab (VEDO) and their relationship with iron metabolism. Materials and Methods: Patients with active IBD initiating induction therapy with IFX or VEDO were included. Serum redox biomarkers (cysteine, homocysteine, free thiols (FTs), glutathione, and thioredoxin-1), inflammatory markers, and iron parameters were measured at baseline and during induction therapy. Patients were stratified according to short-term clinical response at week 14 and long-term response at 1 year. Longitudinal mixed-effects models, correlation analyses, and logistic regression were used to evaluate associations between redox biomarkers, treatment outcomes, and iron metabolism. Results: Fifty-eight patients were included (IFX: n = 37; VEDO: n = 21). Induction therapy resulted in marked reductions in inflammatory markers in short-term responders. Redox biomarkers showed more modest, mostly non-significant, response-dependent patterns. IFX-treated short-term non-responders exhibited non-significant lower cysteine levels than responders at baseline (2,336 vs. 3,611 μg/mL; p > 0.05) and week 14 (2,888 vs. 3,599 μg/mL; p > 0.05). Similarly, homocysteine levels were higher in IFX-treated short-term non-responders at baseline (7,500 vs. 4,260 ng/mL; p < 0.05) and week 14 (7,002 vs. 4,278 ng/mL; p > 0.05), whereas VEDO-treated patients showed comparable levels between response groups. FT levels showed no significant changes, increasing in short-term responders while decreasing in short-term non-responders across both therapies. Glutathione levels showed no major overall changes, although levels between IFX-treated long-term responders and non-responders appeared to differ during induction therapy. Glutathione correlated inversely with transferrin saturation (r = −0.50, p < 0.05) and serum iron (r = −0.46, p < 0.05) after induction therapy. Conclusion: Exploratory analyses suggested treatment response-related differences in cysteine, homocysteine, and FTs in IFX-treated patients, highlighting their potential as biomarkers of treatment response that warrant further investigation. Glutathione demonstrated an association with iron metabolism, suggesting a different biological role. These findings suggest a potential role for redox-iron interactions in treatment response biology that warrant further exploration and validation in larger prospective cohorts.
SN - 1663-9812
ER -