Abstract
Background: It remains uncertain whether vitamin D3 (vitD3) supplementation is beneficial for remission of Crohn's disease (CD). The influence of vitD3 supplementation on Infliximab (IFX) effectiveness was analyzed in Chinese CD patients.Methods: In this retrospective cohort study, moderate-to-severe CD patients, who were bio-naïve and prescribed with IFX treatment for at least 54 weeks, were recorded from January 2014 to December 2019. VitD3 supplementation was defined as patients additionally took oral vitD3 (125 IU/d) within 3 days after the first infusion and persisted in the whole follow-up period. Disease activity was assessed using Harvey-Bradshaw Index (HBI). Serum cytokine profiles (IL-2, IL-4, IL-6, IL-10, TNF-α, and IFN-γ) were quantitatively analyzed in a subset of all patients at baseline and 54-week after intervention.Results: Among 73 enrolled patients, 37 took vitD3 regularly (D3-patients), the others (non-D3-patients) did not. At 54-week, the mean 25-hydroxyvitaminD level increased in D3-patients (20.33 vs. 15.07 ng/mL, P < 0.001). The clinical remission rate was higher in D3-patients compared to non-D3-patients (83.8 vs. 61.6%, P = 0.030). The decrease of HBI from baseline to 54-week was more in D3-patients than non-D3-patients (7.41 ± 3.0 vs. 6.28 ± 2.75, P = 0.023). Furthermore, vitD3 supplementation was independently related to the increase of remission rate at 54-week in D3-patients (β = −1.667, P = 0.015). The benefit of vitD3 supplementation was significant only in patients with deficient vitD3 (all P < 0.05), but not in non-deficient vitD3. A total of nine patients (four non-D3-patients and five D3-patients) were selected to determine serum cytokine profiles after 54-week IFX treatment. In non-D3-patients, the decreases of TNF-α and IL-6 at 54-week were more obvious than at baseline (P = 0.032, 0.022, respectively). In D3-patients, however, only IL-10 increased at 54-week compared with its baseline value (P = 0.037).Conclusions: VitD3 supplementation could improve IFX effectiveness in CD patients, especially for patients with vitD3 deficiency. This beneficial effect of vitD3 supplementation probably arose from the up-regulation of IL-10.Trial Registration: NCT04606017.
Highlights
Inflammatory bowel diseases (IBD) encompass two distinct disorders, Crohn’s disease (CD) and ulcerative colitis (UC)
The studies with genetic knockout of vitD receptor gene (VDR−/−) in experimental models of colitis revealed that Vitamin D receptor gene (VDR)−/− mice were more prone to epithelial injury, which were typically characterized by the loss of intestinal epithelial tight junctions, breakdown in epithelial integrity, and increased bacterial penetration [5, 6]
The results suggested that vitamin D3 (vitD3) supplementation was an independent factor for improving the remission rate of IFX-treated CD patients (β = −1.667, P = 0.015) (Table 3)
Summary
Inflammatory bowel diseases (IBD) encompass two distinct disorders, Crohn’s disease (CD) and ulcerative colitis (UC). As a vital counterbalance to activation of adaptive immunity, vitD could suppress the proliferation of T and B cells, inhibit the expression of various pro-inflammatory cytokines (such as TNF-α), and induce regulatory T cells (Tregs) to secrete anti-inflammatory cytokines (such as IL-10) [7,8,9]. Some of these cytokines have been proven to participate in the pathogenesis of IBD, thereby affecting the efficacy of biologic therapies [10, 11]. The influence of vitD3 supplementation on Infliximab (IFX) effectiveness was analyzed in Chinese CD patients
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