A comparative study of nintedanib versus conventional drugs in the treatment of inflammatory bowel disease-associated intestinal fibrosis.

BACKGROUND

Intestinal fibrosis is a severe complication of inflammatory bowel disease (IBD) with limited effective therapeutic interventions. Nintedanib, a multi-target kinase inhibitor, exerts well-characterized antifibrotic activity in pulmonary fibrosis and may serve as a candidate agent for IBD-related intestinal fibrosis.

OBJECTIVE

To compare the anti-inflammatory and antifibrotic efficacy of nintedanib with prednisolone and sulfasalazine in a DSS-induced mouse intestinal fibrosis model.

METHODS

Forty-eight C57BL/6 mice were randomly allocated to four DSS-treated intervention groups (12 mice per group: Group A prednisolone, Group B sulfasalazine, Group C nintedanib, Group D normal saline), plus a normal untreated control Group E (n = 7). Intestinal fibrosis was induced via four cycles of intermittent 2% DSS drinking water. On Day 26 prior to drug administration, five mice from each group were randomly euthanized for baseline detection to verify successful model establishment. The remaining mice received 14 consecutive days of intragastric treatment. Measured endpoints included body weight recovery, disease activity index (DAI), colon morphological parameters, serum TGF-β and TNF-α levels, and collagen deposition quantified via Masson's trichrome staining.

RESULTS

Group C achieved slightly higher body weight recovery (19.6 ± 1.4%) than Group A (18.7 ± 0.2%) and Group B (19.4 ± 1.5%), while Group D only recovered 3.4 ± 0.9% (P < 0.001). Nintedanib treatment significantly improved colon length and reduced colon weight compared with the two conventional drugs, though colon length in Group C was still markedly shorter than that of normal mice. Serum TGF-β and TNF-α were reduced more substantially in Group C; however, cytokine concentrations remained 2-3 times higher than baseline values of healthy animals and failed to return to normal levels. Masson staining revealed that collagen deposition in Group C decreased by roughly 10% relative to Groups A and B (25±3.2%vs 35±4.2%, 34±3.8%). Currently, there is no unified gold-standard threshold for evaluating antifibrotic efficacy in preclinical intestinal fibrosis models, and relevant quantitative criteria vary widely across published studies.

CONCLUSION

In this DSS-induced colitis model, nintedanib produced modest anti-inflammatory and collagen-reducing effects compared with prednisolone and sulfasalazine used in this study. These preclinical preliminary results warrant further research to evaluate nintedanib as a potential therapeutic candidate for fibrostenotic Crohn's disease.