Effects of Vitamin D Stoss Dosing in Patients with Sickle Cell Disease

Background: The prevalence of vitamin D (Vit D) deficiency is high in patients with sickle cell disease (SCD). The probable factors contributing to this issue include skin pigmentation, inadequate nutrition, elevated body mass index, and renal dysfunction. Given the inherent endothelial dysfunction and pro-inflammatory status of SCD, maintaining an adequate Vit D level in these patients is more crucial. There is no study to date assessing the optimal dosing for Vit D in SCD. This study aimed to assess if administering a single oral very high dose of Vit D called ‘stoss dosing’ (based on patient's age and current Vit D levels) is more effective in the treatment of vit D deficiency than standard supplementation for patients with SCD.

Methods: All patients ≤ 21 years of age with SCD (HbSS, HbSC or HbS beta thalassemia) who received stoss dosing during January-December 2023, after failing at least 1 month trial of standard supplementation of Vit D (serum 25-hydroxy Vit D level <30 ng/mL on 2000 IU daily or 50,000 IU weekly) were included in the study. Stoss dosing was given as a single oral very high dose of ergocalciferol determined based on age and 25-hyroxy Vit D levels on that day while in clinic(1). Retrospective data was collected through chart review at three time points to assess longitudinal levels of Vit D. The timepoints were pre-stoss dosing (when the patients started or were already on standard supplementation of Vit D); on the day of stoss dosing; and post-stoss dosing within a year of receiving the dose. Vaso-occlusive crisis (VOC) episodes requiring ED visits or hospital admissions one year before and after the stoss dosing were also recorded for secondary assessment of the effect of stoss dosing on frequency of VOC episodes in patients with SCD.

Results: A total of 46 patients that met inclusion criteria were identified. The mean initial Vit D level pre- stoss dosing was 17.6 ng/mL. At this time the patients either started or continued their standard Vit D supplementation. These patients were then followed up for a median of 8.3 months receiving standard dosing of Vit D before the stoss dose was given. On the day of the stoss dose the Vit D levels were reassessed and mean Vit D level while being on standard dosing was 15.2 ng/mL. These results showed no clinical improvement while being on standard dosing of Vit D rather an overall decline (p=0.002). The follow up mean Vit D level post stoss dosing with a median of 2.8 months follow up was 38.4 ng/mL, showing a significant improvement in Vit D levels (p=<0.0001). The mean number of ED visits and hospital admissions for VOC pain 1 year before the stoss dosing was 1.1 visit vs 1.3 visit, 1 year post stoss dosing. Each patient served as his or her own control in terms of sickle cell disease burden and demographic status.

Conclusions: Our results highlight the effectiveness of stoss dosing in resolution of Vit D deficiency for this vulnerable population that has been difficult to achieve with standard dosing. Based on our data the stoss dosing was well tolerated by patients with no significant side effects. An advantage of stoss dosing is that it enhances compliance due to its administration in a clinic setting as a single, one-time dose. However, a drawback is that it is not suitable for patients who are unable to swallow pills. The effect of stoss dosing on frequency of VOC episodes and other SCD outcomes will need to be further explored in larger studies with more prospective data. It is also unclear how often repeat dosing will be required. However, these results highlight a potential for easy, low-cost intervention with significant benefits in patients with sickle cell disease.

Reference:

1. Cleppe J, Amelon E, Dunham K, Rumelhart S, Modi A. Single High-Dose Oral Vitamin D3 (Stoss Dose) in Lieu of Daily Dosing is Reliably Effective for Treatment of Vitamin D Insufficiency/Deficiency in Pediatric Hematopoetic Stem Cell Transplant (HSCT) Recipients. Biology of Blood and Marrow Transplantation. 2018 Mar;24(3): S333.

Crary:Medexus: Membership on an entity's Board of Directors or advisory committees; ASC Therapeutics: Consultancy; Sanofi: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy.