Effect of Vitamin D<sub>3</sub>on Asthma Treatment Failures in Adults With Symptomatic Asthma and Lower Vitamin D Levels
Authors: Mario Castro, Tonya S. King, Susan J. Kunselman, Michael D. Cabana, Loren Denlinger, Fernando Holguin, Shamsah D. Kazani, Wendy C. Moore, James Moy, Christine A. Sorkness, Pedro Avila, Leonard B. Bacharier, Eugene Bleecker, Homer A. Boushey, James Chmiel, Anne M. Fitzpatrick, Deborah Gentile, Mandeep Hundal, Elliot Israel, Monica Kraft, Jerry A. Krishnan, Craig LaForce, Stephen C. Lazarus, Robert Lemanske, Njira Lugogo, Richard J. Martin, David T. Mauger, Edward Naureckas, Stephen P. Peters, Wanda Phipatanakul, Loretta G. Que, Ajay Sheshadri, Lewis Smith, Julian Solway, Lisa Sullivan-Vedder, Kaharu Sumino, Michael E. Wechsler, Sally Wenzel, Steven R. White, E. Rand Sutherland
Journal: JAMA (2014)

IMPORTANCEIn asthma and other diseases, vitamin D insufficiency is associated with adverse outcomes.It is not known if supplementing inhaled corticosteroids with oral vitamin D 3 improves outcomes in patients with asthma and vitamin D insufficiency.OBJECTIVE To evaluate if vitamin D supplementation would improve the clinical efficacy of inhaled corticosteroids in patients with symptomatic asthma and lower vitamin D levels. DESIGN, SETTING, AND PARTICIPANTSThe VIDA (Vitamin D Add-on Therapy Enhances Corticosteroid Responsiveness in Asthma) randomized, double-blind, parallel, placebo-controlled trial studying adult patients with symptomatic asthma and a serum 25-hydroxyvitamin D level of less than 30 ng/mL was conducted across 9 academic US medical centers in the National Heart, Lung, and Blood Institute's AsthmaNet network, with enrollment starting in April 2011 and follow-up complete by January 2014.After a run-in period that included treatment with an inhaled corticosteroid, 408 patients were randomized.INTERVENTIONS Oral vitamin D 3 (100 000 IU once, then 4000 IU/d for 28 weeks; n = 201) or placebo (n = 207) was added to inhaled ciclesonide (320 μg/d).If asthma control was achieved after 12 weeks, ciclesonide was tapered to 160 μg/d for 8 weeks, then to 80 μg/d for 8 weeks if asthma control was maintained. MAIN OUTCOMES AND MEASURESThe primary outcome was time to first asthma treatment failure (a composite outcome of decline in lung function and increases in use of β-agonists, systemic corticosteroids, and health care).RESULTS Treatment with vitamin D 3 did not alter the rate of first treatment failure during 28 weeks (28% [95% CI, 21%-34%] with vitamin D 3 vs 29% [95% CI, 23%-35%] with placebo; adjusted hazard ratio, 0.9 [95% CI, 0.6-1.3]).Of 14 prespecified secondary outcomes, 9 were analyzed, including asthma exacerbation; of those 9, the only statistically significant outcome was a small difference in the overall dose of ciclesonide required to maintain asthma control (111.3 μg/d [95% CI, 102.2-120.4μg/d] in the vitamin D 3 group vs 126.2 μg/d [95% CI, 117.2-135.3μg/d] in the placebo group; difference of 14.9 μg/d [95% CI, 2.1-27.7 μg/d]).CONCLUSIONS AND RELEVANCE Vitamin D 3 did not reduce the rate of first treatment failure or exacerbation in adults with persistent asthma and vitamin D insufficiency.These findings do not support a strategy of therapeutic vitamin D 3 supplementation in patients with symptomatic asthma.