Vitamin D Gets Mixed Results in Prospective Asthma Trial

Jim Kling

May 20, 2014

SAN DIEGO — Vitamin D supplementation has no significant effect on the overall rate of first treatment failure or exacerbation in patients with asthma and low vitamin D levels, according to the Vitamin D Add-on Therapy Enhances Corticosteroid Responsiveness in Asthma (VIDA) trial.

However, in subjects who reached normal vitamin D levels, there were significant reductions in exacerbations and the rate of first treatment failure.

"In terms of risk/benefit, there's enough potential for a benefit and the risk is low. But for it to be a public health statement, we have to be more conservative," said lead investigator Mario Castro, MD, professor of medicine and pediatrics at Washington University in St. Louis, Missouri.

The results were presented here at the American Thoracic Society 2014 International Conference and published online simultaneously in JAMA.

Retrospective studies have linked serum 25-hydroxyvitamin D levels below 30 ng/mL to airway hyper-responsiveness, impaired lung function, increased exacerbation frequency, and reduced corticosteroid responsiveness. It has also been suggested that vitamin D enhances the anti-inflammatory effect of corticosteroids.

Dr. Castro and colleagues evaluated 408 adults with symptomatic asthma and a serum 25-hydroxyvitamin D level below 30 ng/mL at 9 medical centers in the United States that belong to AsthmaNet, the National Heart, Lung, and Blood Institute asthma network.

Patients were randomized to receive an initial dose of 100,000 IU of oral vitamin D₃ followed by 4000 IU/day for 28 weeks (n = 201) or placebo (n = 207).

All patients used inhaled ciclesonide 320 µg/day. When asthma control was achieved after 12 weeks, the dose of ciclesonide was reduced to 160 µg/day for 8 weeks. If control was maintained, the dose was reduced to 80 µg/day for another 8 weeks.

The study did not meet its primary outcome. There was no difference in the time to first treatment failure — defined as a decline in lung function and increased use of beta-agonists, systemic corticosteroids, and healthcare — between the vitamin D and placebo groups (adjusted hazard ratio [HR], 0.9; 95% confidence interval [CI], 0.6 - 1.3; P = .54)

It also did not meet its key secondary outcome. There was no difference in the of number of exacerbation events between the vitamin D and placebo groups (adjusted HR, 0.63; 95% CI, 0.39 - 1.01; P = .05).

However, at 28 weeks, there was a significant difference in cumulative ciclesonide dosing between the vitamin D and placebo groups (111.3 vs 126.2 µg/day; P = .02).

In addition, "the overall asthma treatment failure was significantly reduced and the exacerbations were significantly reduced in subjects that got to a normal vitamin D level," said Dr. Castro reported.

In the vitamin D group, 82% of participants responded to treatment and achieved a serum 25-hydroxyvitamin D level of at least 30 ng/mL. Overall rates of treatment failure were significantly lower in this subset of responders than in the placebo group (adjusted HR, 0.6; 95% CI, 0.4 - 0.9; P = .03), as were exacerbations (adjusted HR, 0.5; 95% CI, 0.3 - 0.8; P = .01).

Dr. Castro's "gut feeling" is that vitamin D supplementation will prove to be useful in at least some people with asthma who have low vitamin D. He said he plans to study exacerbations in children who achieve sufficient vitamin D levels.

Vitamin D biology is difficult to study, said David Thickett, MD, senior lecturer at the University of Birmingham, United Kingdom, who attended the session.

Different skin colors and wearing protective clothing in the sun, for example, can be important confounders. "It's quite difficult to get a clean baseline," he said. However, this is an "encouraging study that suggests more work is needed," Dr. Thickett told Medscape Medical News.

He said he believes that vitamin D trials might do better to focus on patients with more severe vitamin D deficiency. "When you've got a signal from those patients, because they're the ones who might benefit the most, then you can extrapolate to the general population," he explained.

The study was funded by the National Heart, Lung, and Blood Institute. Dr. Castro and Dr. Thickett have disclosed no relevant financial relationships.

American Thoracic Society (ATS) 2014 International Conference. Presented May 18, 2014.

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