Despite previous evidence of its anti-inflammatory effects, high doses of vitamin D did not reduce the incidence of endoscopic or clinical recurrence of Crohn’s disease in patients who underwent ileocolonic resection with anastomosis, a placebo-controlled study from Belgium and the Netherlands found.
“Vitamin D at a dose of 25,000 IU/week orally did not reduce endoscopic or clinical recurrence compared to placebo, despite doubling of the serum concentrations,” Geert D’Haens, MD, PhD, of Amsterdam University Medical Centre, and associates wrote in Clinical Gastroenterology and Hepatology.
Debate is ongoing whether vitamin D deficiency is a cause or consequence of active Crohn’s disease, since deficiency of this vitamin is common in these patients, and interventional trials have provided no conclusive answers so far. But some research has suggested vitamin D may play a bidirectional role in the inflammation of Crohn’s disease.
According to the authors, who said theirs is the first study to monitor Crohn’s disease activity endoscopically during vitamin D therapy, a postoperative trial is “an excellent model for truly investigating the anti-inflammatory effect of, in this case, vitamin D, since following resection the disease could be considered as a ‘reset to zero’ thereby diminishing possible confounding factors as concomitant immunomodulating medication and disease activity.”
They randomized 143 patients 1:1 to vitamin D or placebo in double-blind fashion at 17 Dutch and Belgian hospitals from February 2014 through June 2017. Median age was 32 (interquartile range 25-43), and about 60% were women. At time of surgery, 25 had an inflammatory disease phenotype, 75 had stricturing disease, 36 had a penetrating phenotype by Montreal classification, and 29 had undergone previous surgery. The two groups were well balanced in demographic and disease characteristics.
Participants were assessed at baseline and weeks 2, 6, 12, and 26 for laboratory and clinical parameters and underwent ileocolonoscopy at 26 weeks.
The primary endpoint was endoscopic recurrence (a modified Rutgeerts score ≥i2b, assessed by blinded readers) at 26 weeks. Secondary endpoints included clinical recurrence (Crohn’s Disease Activity Index ≥220) and outcomes associated with patients’ baseline serum concentrations of vitamin D. Changes in quality of life were measured by three instruments, the Short Form-36 Health Survey, the IBD Questionnaire, and the EuroQol 5 Dimensions Questionnaire.
In the vitamin D group, serum levels of 25-hydroxy vitamin D (25-OH-D) increased from a median of 42 nmol/L at baseline to 81 nmol/L at week 26 (P<0.00001), while levels in the placebo group remained unchanged at 43 nmol/L.
In the intention-to-treat analysis, the proportion of patients with endoscopic recurrence at 26 weeks did not differ significantly between the vitamin D and placebo arms (58% vs 66%, P=0.037). Nor did the cumulative rate of clinical recurrence differ significantly between the two groups: 18.1% in the vitamin D group vs 18.3% in the placebo group (P=0.91). Quality of life improved slightly over time in both groups but, again, was not notably different in the two arms (P=0.07).
In line with previous research, current smoking was associated with numerically higher risk for postoperative recurrence, which did not reach statistical significance.
Although significant in Western populations, seasonal variations in 25-OH-D concentrations were minimized over the study’s 3-year, all-season recruitment, and the season in which patients were enrolled had no effect on endoscopic recurrence.
As for safety, 182 adverse events occurred in the vitamin D group and 155 in the placebo group, with 25% relating to surgery.
D’Haens and colleagues acknowledged several study limitations, including an unexpectedly high dropout rate of 18.2%, which prevented achievement of the targeted sample size. Furthermore, all patients received 25,000 IU vitamin D irrespective of serum vitamin D level, but a treat-to-target study design in order to reach serum 25-OH-D levels >75 nmol/L might arguably have been better.
Disclosures
This trial was financially supported by the Broad Medical Research Program/Crohn’s and Colitis Foundation and the International Organization for Inflammatory Bowel Diseases. Vitamin D and placebo were provided by SMB Pharma.
The authors reported having no conflicts of interest.
Source: MedicalNewsToday.com
