In the Journals

Low vitamin D linked to higher UC relapse risk among patients in remission

Low serum vitamin D levels increased the risk for relapse in ulcerative colitis patients who were in clinical remission, according to prospective study data.

These findings support routine surveillance of serum vitamin D levels in UC patients, and provide a rationale for supplementation in maintenance therapy, investigators concluded.

“We showed that vitamin D levels are associated with baseline endoscopic and histologic inflammation severity during clinical remission, and are associated independently with the longitudinal risk of clinical relapse,” John Gubatan, MD, and colleagues from the department of medicine, division of gastroenterology and hepatology at Beth Israel Deaconess and Harvard Medical School in Boston, wrote. “These results suggest that vitamin D status is linked not only to current disease severity, but also has an impact on future risk of clinical relapse.”

To clarify the clinical significance of low vitamin D levels in patients whose UC is in remission, Gubatan and colleagues performed a physician-blinded prospective study of 70 patients with a score of two or less on the Simple Clinical Colitis Activity Index, whom they recruited after a surveillance colonoscopy at the IBD Center at Beth Israel Deaconess between 2009 and 2012.

They used an enzyme-linked immunosorbent assay to measure serum levels of 25-hydroxy-vitamin D at baseline, and followed patients for 12 months to assess for clinical relapse.

Sixty percent of patients reported taking vitamin D supplements, the researchers noted.

Overall, 20% of patients with a vitamin D level at or below 35 ng/mL at baseline relapsed compared with 9% of patients with a vitamin D level that exceeded that threshold (P = .003).

The investigators found that the mean vitamin D level at baseline was lower in patients who ended up relapsing during the follow-up period (29.5 ng/mL vs. 50.3 ng/mL; P = .001).

Additionally, they found that a vitamin D level less than 35 ng/mL during remission was associated with an increased risk for clinical relapse over 1 year, independent of endoscopic or histologic grade at baseline (OR = 1.25; 95% CI, 1.01-1.56).

They also found that low baseline vitamin D levels were independently associated with increased endoscopic inflammation (OR = 1.29; 95% CI, 1.07-1.85) and histologic inflammation (OR = 1.46; 95% CI, 1.13-1.88) at baseline.

The receiver operating characteristic curve of baseline vitamin D levels for the outcome of 1-year clinical relapse had an area under the curve of 0.72 (P < .01). Further, and a serum level of 35 ng/mL or less predicted the risk for clinical relapse with 70% sensitivity (95% CI; 46-88) and 74% specificity (95%; CI 57-83).

“Our study provides evidence that low vitamin D levels ... correlate with endoscopic and histologic inflammation and are associated with an increased risk of subsequent clinical relapse during periods of clinical remission,” the investigators concluded. “Vitamin D is an affordable, accessible, and relatively nontoxic supplement that may have protective effects in the maintenance of clinical remission in patients with ulcerative colitis. Clinical trials of vitamin D therapy to obtain vitamin D levels above this threshold should be considered to definitively establish its impact on ulcerative colitis outcomes.”

Stephen B. Hanauer, MD

Stephen B. Hanauer

Despite the strengths of this study, including its prospective and blinded design, “more unknowns remain unknown that unmask residual uncertainties,” Stephen B. Hanauer, MD, of the department of medicine and the Digestive Health Center at Northwestern University Feinberg School of Medicine in Chicago, wrote in a related editorial.

These include the 35 ng/mL vitamin D cut-off level, which falls between what is considered the normal range (20-40 ng/mL), as well as the “confidence intervals regarding the risk of relapse at lower or higher vitamin D levels, in which there does not appear to be a dose-response in the odds ratios according to levels,” he wrote. “Hence, we are left with another association with unproven causation or confirmed pathogenesis ... As numerous investigators and editorialists have urged, prospective trials are needed.” – by Adam Leitenberger

Disclosures: The researchers and Hanauer report no relevant financial disclosures.

Low serum vitamin D levels increased the risk for relapse in ulcerative colitis patients who were in clinical remission, according to prospective study data.

These findings support routine surveillance of serum vitamin D levels in UC patients, and provide a rationale for supplementation in maintenance therapy, investigators concluded.

“We showed that vitamin D levels are associated with baseline endoscopic and histologic inflammation severity during clinical remission, and are associated independently with the longitudinal risk of clinical relapse,” John Gubatan, MD, and colleagues from the department of medicine, division of gastroenterology and hepatology at Beth Israel Deaconess and Harvard Medical School in Boston, wrote. “These results suggest that vitamin D status is linked not only to current disease severity, but also has an impact on future risk of clinical relapse.”

To clarify the clinical significance of low vitamin D levels in patients whose UC is in remission, Gubatan and colleagues performed a physician-blinded prospective study of 70 patients with a score of two or less on the Simple Clinical Colitis Activity Index, whom they recruited after a surveillance colonoscopy at the IBD Center at Beth Israel Deaconess between 2009 and 2012.

They used an enzyme-linked immunosorbent assay to measure serum levels of 25-hydroxy-vitamin D at baseline, and followed patients for 12 months to assess for clinical relapse.

Sixty percent of patients reported taking vitamin D supplements, the researchers noted.

Overall, 20% of patients with a vitamin D level at or below 35 ng/mL at baseline relapsed compared with 9% of patients with a vitamin D level that exceeded that threshold (P = .003).

The investigators found that the mean vitamin D level at baseline was lower in patients who ended up relapsing during the follow-up period (29.5 ng/mL vs. 50.3 ng/mL; P = .001).

Additionally, they found that a vitamin D level less than 35 ng/mL during remission was associated with an increased risk for clinical relapse over 1 year, independent of endoscopic or histologic grade at baseline (OR = 1.25; 95% CI, 1.01-1.56).

They also found that low baseline vitamin D levels were independently associated with increased endoscopic inflammation (OR = 1.29; 95% CI, 1.07-1.85) and histologic inflammation (OR = 1.46; 95% CI, 1.13-1.88) at baseline.

The receiver operating characteristic curve of baseline vitamin D levels for the outcome of 1-year clinical relapse had an area under the curve of 0.72 (P < .01). Further, and a serum level of 35 ng/mL or less predicted the risk for clinical relapse with 70% sensitivity (95% CI; 46-88) and 74% specificity (95%; CI 57-83).

“Our study provides evidence that low vitamin D levels ... correlate with endoscopic and histologic inflammation and are associated with an increased risk of subsequent clinical relapse during periods of clinical remission,” the investigators concluded. “Vitamin D is an affordable, accessible, and relatively nontoxic supplement that may have protective effects in the maintenance of clinical remission in patients with ulcerative colitis. Clinical trials of vitamin D therapy to obtain vitamin D levels above this threshold should be considered to definitively establish its impact on ulcerative colitis outcomes.”

Stephen B. Hanauer, MD

Stephen B. Hanauer

Despite the strengths of this study, including its prospective and blinded design, “more unknowns remain unknown that unmask residual uncertainties,” Stephen B. Hanauer, MD, of the department of medicine and the Digestive Health Center at Northwestern University Feinberg School of Medicine in Chicago, wrote in a related editorial.

These include the 35 ng/mL vitamin D cut-off level, which falls between what is considered the normal range (20-40 ng/mL), as well as the “confidence intervals regarding the risk of relapse at lower or higher vitamin D levels, in which there does not appear to be a dose-response in the odds ratios according to levels,” he wrote. “Hence, we are left with another association with unproven causation or confirmed pathogenesis ... As numerous investigators and editorialists have urged, prospective trials are needed.” – by Adam Leitenberger

Disclosures: The researchers and Hanauer report no relevant financial disclosures.

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