Dataset Information

Vitamin D metabolites are lower with active Crohn's disease and spontaneously recover with development of remission.

ABSTRACT:

Background

Vitamin D deficiency is associated with active Crohn's disease (CD). However, it remains unclear if lower 25-hydroxyvitamin D [25(OH)D] concentration is the cause, or consequence, of intestinal inflammation. Existing literature has focused on circulating 25(OH)D rather than the active metabolite 1,25(OH)₂D, or its breakdown product, 24,25(OH)₂D. We aimed to characterise vitamin D metabolism in a cohort of patients with active and inactive CD.

Methods

Fifty-four patients with CD and not on corticosteroids or vitamin D supplements, were enrolled in a 6-month prospective cohort study. Sera were collected on enrolment and at 6?months and tested for 25(OH)D, 1,25(OH)₂D, 24,25(OH)₂D using liquid chromatography tandem mass spectroscopy as well as vitamin-D-binding protein.

Results

There were no differences in 25(OH)D or 1,25(OH)₂D levels between participants with active versus inactive disease. Levels of 24,25(OH)₂D were significantly lower in those with active compared with inactive disease (mean 3.9 versus 6.0?µmol/l; p?=?0.007) and therefore the ratio of 25(OH)D:24,25(OH)₂D was higher (mean 17.3 versus 11.1; p?=?0.001). In those patients with active disease who achieved remission, there was a mean increase in 25(OH)D of 32.3?nmol/l (i.e. to a level in the sufficient range) and 24,25(OH)₂D of 2.1?µmol/l. These increases were not seen in patients with persistently active or inactive disease.

Conclusion

Levels of 24,25(OH)₂D, but not 25(OH)D, were lower in patients with active CD, and spontaneously increased with resolution of underlying inflammation. The utility of 24,25(OH)₂D as a biomarker of disease activity and vitamin D status in CD warrants further exploration.

SUBMITTER: Haifer C

PROVIDER: S-EPMC6661794 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroundCrohn's disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract, in which the pathogenesis is believed to be partly influenced by the gut microbiome. Probiotics can be used to manipulate the microbiome and have therefore been considered as a potential therapy for CD. There is some evidence that probiotics benefit other gastrointestinal conditions, such as irritable bowel syndrome and ulcerative colitis, but their efficacy in CD is unclear. This is the first update of a Cochrane Review previously published in 2008.ObjectivesTo assess the efficacy and safety of probiotics for the induction of remission in CD.Search methodsThe following electronic databases were searched: MEDLINE (from inception to 6 July 2020), Embase (from inception to 6 July 2020), the Cochrane Central Register of Controlled Trials (CENTRAL), The Cochrane IBD Review Group Specialised Trials Register, World Health Organization (WHO) International Clinical Trials Registry, and ClinicalTrials.gov.Selection criteriaRandomised controlled trials (RCTs) that compared probiotics with placebo or any other non-probiotic intervention for the induction of remission in CD were eligible for inclusion.Data collection and analysisTwo review authors independently extracted data and assessed the methodological quality of included studies. The primary outcome was clinical remission. Risk ratios (RRs) and 95% confidence intervals (CIs) were calculated for dichotomous outcomes.Main resultsThere were two studies that met criteria for inclusion. One study from Germany had 11 adult participants with mild-to-moderate CD, who were treated with a one-week course of corticosteroids and antibiotics (ciprofloxacin 500 mg twice daily and metronidazole 250 mg three times a day), followed by randomised assignment to Lactobacillus rhamnosus strain GG (two billion colony-forming units per day) or corn starch placebo. The other study from the United Kingdom (UK) had 35 adult participants with active CD (CDAI score of 150 to 450) randomised to receive a synbiotic treatment (comprised of freeze-dried Bifidobacterium longum and a commercial product) or placebo. The overall risk of bias was low in one study, whereas the other study had unclear risk of bias in relation to random sequence generation, allocation concealment, and blinding. There was no evidence of a difference between the use of probiotics and placebo for the induction of remission in CD (RR 1.06; 95% CI 0.65 to 1.71; 2 studies, 46 participants) after six months. There was no difference in adverse events between probiotics and placebo (RR 2.55; 95% CI 0.11 to 58.60; 2 studies, 46 participants). The evidence for both outcomes was of very low certainty due to risk of bias and imprecision.Authors' conclusionsThe available evidence is very uncertain about the efficacy or safety of probiotics, when compared with placebo, for induction of remission in Crohn's disease. There is a lack of well-designed RCTs in this area and further research is needed.

Project description:BACKGROUND:Crohn's disease (CD) is a chronic inflammatory disease of the gastrointestinal tract, and immune response modulation is the main treatment strategy to induce remission in active CD. Certolizumab pegol (CZP) is a tumor necrosis factor-alfa (TNF-?) inhibitor which regulates impaired immune response. OBJECTIVES:The primary objectives were to evaluate the efficacy and safety of CZP for the induction of remission in CD. SEARCH METHODS:We searched MEDLINE, Embase, CENTRAL, the Cochrane IBD group specialized register, trials registers and other sources from inception to 28 January 2019. Moreover, we contacted the pharmaceutical company that manufactures CZP. SELECTION CRITERIA:We included randomized controlled trials comparing CZP with placebo or no treatment in active CD patients. DATA COLLECTION AND ANALYSIS:We used standard Cochrane methodological procedures. The main outcomes selected for GRADE analysis were clinical remission at week 8 (Crohn's Disease Activity Index [CDAI] ?150), clinical response at week 8 (CDAI reduction ? 100 or clinical remission), and serious adverse events. The Mantel-Haenszel random-effects method was applied for the statistical analyses. For dichotomous outcomes, we calculated the risk ratio (RR) and corresponding 95% confidence interval (95% CI). MAIN RESULTS:Four studies involving 1485 participants with moderate to severe CD met the inclusion criteria and were used in the meta-analyses. All studies included active CD patients with CDAI ranging from 220 to 450. Most patients were adults over 18 years of age. One study was identified as high risk of bias due to a non-identical placebo while the other studies were judged to be at low risk of bias.CZP (100 mg to 400 mg every 2 to 4 weeks) was shown to be superior to placebo for achieving clinical remission at week 8 (RR 1.36, 95% CI 1.11 to 1.66; moderate certainty evidence). The raw numbers of participants achieving clinical remission at week 8 were 26.9% (225/835) and 19.8% (129/650) in the CZP and the placebo groups, respectively.CZP was shown to be superior to placebo for achieving clinical response at week 8 (RR 1.29, 95% CI 1.09 to 1.53; moderate certainty evidence). In raw numbers, clinical response at week 8 was achieved in 40.2% (336/835) and 30.9% (201/650) of participants in the CZP and the placebo groups, respectively.In raw numbers, serious adverse events were observed in 8.7% (73/835) and 6.2% (40/650) of participants in the CZP and the placebo groups, respectively (RR 1.35, 95% CI 0.93 to 1.97; moderate certainty evidence). Serious adverse events included worsening Crohn's disease, infections, and malignancy. AUTHORS' CONCLUSIONS:Moderate certainty evidence suggests that CZP is effective for induction of clinical remission and clinical response in participants with active CD patients. It is uncertain whether the risk of serious adverse events differs between CZP and placebo as the 95% CI includes the possibility of a small decrease or doubling of events. Future studies are needed to evaluate the long-term efficacy and safety of CZP in CD patients.