Safety and efficacy of high-dose interval vitamin D therapy in pediatric patients with inflammatory bowel disease
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Citation
Abstract
BACKGROUND: Vitamin D Deficiency is becoming increasingly common in eastern and western societies due to geographic and lifestyles constraints. Maintaining optimal vitamin D levels is crucial for absorbing key minerals such as calcium and phosphorus and for the proper upkeep of bone density, especially in children and adolescents. Long-term daily supplementation has proven ineffective due to non-compliance. Patients suffering from Inflammatory Bowel Disease (IBD) are similarly at increased risk of being vitamin D deficient due to medication non-compliance. In addition, the complex intestinal pathology observed in patients with IBD can hinder optimal intestinal absorption of dietary vitamin D. Recent studies on vitamin D also highlight its role in supporting the systemic and intestinal immune systems. Therefore, efforts to optimize vitamin D administration are particularly important to children with IBD who are at risk for nutritional deficiency and immune dysregulation.
OBJECTIVES: The focus of this study is to evaluate the safety and efficacy of high-dose oral vitamin D therapy administered concurrently with scheduled infliximab or vedolizumab infusions. The primary clinical outcome is assessing the percentage of patients that reach target serum 25-hydroxyvitamin D (25-OHD) values between 40 ng/mL and 60 ng/mL by the end of the study.
METHODS: We recruited a cohort of 23 pediatric patients with IBD that were deficient in vitamin D (serum 25-OHD <30 ng/mL) and were being treated with either infliximab or vedolizumab. Study enrollment began in October 2020. Based on the interval for scheduled infliximab or vedolizumab infusions (4 to 6 weeks or 6 to 8 weeks), patients were given an initial dose of either 2,500 mCg or 5,000 mCg of vitamin D3 (cholecalciferol), respectively, for four visits. Serum 25-OHD levels were subsequently reevaluated in each participant. Vitamin D3 doses for the next four visits were adjusted to achieve a serum 25-OHD level between 40 and 60 ng/mL in all study subjects. Periodic checks for hypercalciuria were conducted, and routine blood chemistry panels were monitored to ensure the safety of all study participants.
RESULTS: Mean serum 25-OHD increased by 14.16 ± 5.28 ng/mL for all patients who received at least three high-doses (2,500 mCg or 5,000 mCg) of vitamin D3. Out of eleven patients who started the study with suboptimal vitamin D status, all but three achieved sufficient or optimal vitamin D status (>30.0 ng/mL). The mean serum 25-OHD increment for the four patients who have completed the study to date has been 11.72 ± 20.15 ng/mL. We observe decreased urine calcium-creatinine ratios in many of our study patients at midpoint visits compared to baseline, despite only minimal changes in urine calcium and creatinine excretion. Other blood chemistry parameters, including serum albumin and liver enzymes, did not change from baseline. Finally, IMPACT-III quality of life assessment scores were not significantly affected by high-dose vitamin D therapy in participants who completed the study.
CONCLUSION: High-Dose Interval oral vitamin D therapy is effective and safe in pediatric patients with IBD currently receiving infliximab or vedolizumab treatment. Supplementing vitamin D at routine infusion visits (and under direct observation) also mitigates non-compliance and could be expanded to treat other nutrient deficiencies. Future studies should explore the potential utility of patients receiving other medications during scheduled infusions or in patients without IBD. Future studies should also assess changes in bone density measurements to better understand the clinical benefits of high-dose interval vitamin D therapy on skeletal health.