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Evaluation of Clinical Outcomes by Therapeutic Dosing Interval of Denosumab (Prolia®) and Calcium-Vitamin D Prescriptions

Denosumab (Prolia®)의 투여 간격 및 칼슘·비타민 D 복합제제 처방 여부에 따른 임상적 결과 평가

  • Kim, Youkyeong (Department of Pharmacy, Seoul National University Bundang Hospital) ;
  • Kim, Junghyun (Department of Pharmacy, Seoul National University Bundang Hospital) ;
  • Doh, Hyunjeong (Department of Pharmacy, Seoul National University Bundang Hospital) ;
  • Jeong, Young Mi (Department of Pharmacy, Seoul National University Bundang Hospital) ;
  • Lee, Jeonghwa (Department of Pharmacy, Seoul National University Bundang Hospital) ;
  • Lee, Ju-Yeun (College of Pharmacy & Research Institute of Pharmaceutical Sciences, Seoul National University) ;
  • Lee, Euni (College of Pharmacy & Research Institute of Pharmaceutical Sciences, Seoul National University)
  • 김유경 (분당서울대학교병원 약제부) ;
  • 김정현 (분당서울대학교병원 약제부) ;
  • 도현정 (분당서울대학교병원 약제부) ;
  • 정영미 (분당서울대학교병원 약제부) ;
  • 이정화 (분당서울대학교병원 약제부) ;
  • 이주연 (서울대학교 약학대학) ;
  • 김은경 (서울대학교 약학대학)
  • Received : 2022.08.11
  • Accepted : 2022.08.20
  • Published : 2022.09.30

Abstract

Background: Denosumab (Prolia®) is administered every 6 months for osteoporosis treatment. Co-administration of calcium and vitamin D is required to minimize hypocalcemia risk. We evaluated clinical outcomes based on the administration interval of denosumab and co-prescription with calcium-vitamin D combination products. Methods: A retrospective study was conducted using electronic medical records from 668 patients who started denosumab therapy between January 1 and December 31, 2018, at Seoul National University Bundang Hospital. Clinical outcomes, as measured by changes in T-score, were evaluated by the intervals and concurrent prescriptions with calcium-vitamin D combination products. Results: Of the 668 patients, 333 patients met the eligibility criteria. These patients were divided into two groups based on appropriateness of the administration interval: "Appropriate" (304 patients, 91.3%) and "Inappropriate" (29 patients, 8.3%). T-score changes were significantly higher in the "Appropriate" than in the "Inappropriate" group (0.30±0.44 vs. 0.13±0.37, p=0.048). At the beginning of the treatment, 221 patients (66.4%) were prescribed calcium-vitamin D combination products, but the changes in T-scores were not significantly different by the prescription status of the product (0.29±0.46 vs. 0.28±0.38, p=0.919). Conclusion: T-scores were significantly improved in patients with appropriate administration intervals. No significant changes in T-scores were observed by the prescription status with calcium-vitamin D combination products. For optimal treatment outcomes, prescribers should encourage adherence to the approved prescription information on dosage and administration, and pharmacists should provide medication counseling for patients.

Keywords

References

  1. The Korean Society of Osteoporosis. Osteoporosis and Osteoporotic Fracture Fact Sheet 2019. Available from https://www.ksbmr.org/bbs/index.html?code=fact&category=&gubun=&page=1&number=703&mode=view&keyfield=&key=. Accessed Feburary 19, 2022.
  2. Choi SH, Kim DY, Koo JW, Lee SG, Jeong SY, Kang CN. Incidence and Management Trends of Osteoporotic Vertebral Compression Fractures in South Korea: A Nationwide Population-Based Study. Asian Spine J 2020;14(2):220-8. https://doi.org/10.31616/asj.2019.0051
  3. Cummings SR, San Martin J, McClung MR, et al. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med 2009;361(8):756-65. https://doi.org/10.1056/NEJMoa0809493
  4. Cummings SR, Ferrari S, Eastell R, et al. Vertebral fractures after discontinuation of denosumab: A post hoc analysis of the randomized placebo-controlled FREEDOM trial and Its extension. J Bone Miner Res 2018;33(2):190-8. https://doi.org/10.1002/jbmr.3337
  5. Daga N, Joseph F. Denosumab-induced severe hypocalcaemia in a patient with vitamin D deficiency. BMJ Case Rep 2020;13(8):e234508. https://doi.org/10.1136/bcr-2020-234508
  6. Nakamura Y, Suzuki T, Kamimura M, et al. Vitamin D and calcium are required at the time of denosumab administration during osteoporosis treatment. Bone Res 2017;5:17021. https://doi.org/10.1038/boneres.2017.21
  7. Carroll R, Matfin G. Endocrine and metabolic emergencies: hypocalcaemia. Ther Adv Endocrinol Metab 2010;1(1):29-33. https://doi.org/10.1177/2042018810366494
  8. Camacho PM, Petak SM, Binkley N, et al. American Association of Clinical Endocrinologists/American College of Endocrinology Clinical Practice Guidelines for the Diagnosis and Treatment of Postmenopausal Osteoporosis-2020 Update. Endocr Pract 2020; 26(Suppl 1):1-46.
  9. Bekker PJ, Holloway DL, Rasmussen AS, et al. A single-dose placebo-controlled study of AMG 162, a fully human monoclonal antibody to RANKL, in postmenopausal women. J Bone Miner Res 2004;19(7):1059-66. https://doi.org/10.1359/JBMR.040305
  10. AMGEN. Approved package insert of Prolia® Pre-filled Syringe. Available from http://www.amgen.co.kr/products/prolia. Accessed Feburary 19, 2022.
  11. Endocrine Today. Denosumab increasingly prescribed in osteoporosis treatment. Available from https://www.healio.com/news/endocrinology/20210329/denosumab-increasinglyprescribed-in-osteoporosis-treatment. Accessed April 17, 2022.
  12. Fleish H. Bisphosphonates in bone disease. From the Laboratory to Patient, 4th ed. San Diego: Academic Press 2000: 30-3.
  13. Bone HG, Wagman RB, Brandi ML, et al. 10 years of denosumab treatment in postmenopausal women with osteoporosis: results from the phase 3 randomised FREEDOM trial and open-label extension. Lancet Diabetes Endocrinol 2017;5(7):513-23. https://doi.org/10.1016/S2213-8587(17)30138-9
  14. Bone HG, Bolognese MA, Yuen CK, et al. Effects of Denosumab Treatment and Discontinuation on Bone Mineral Density and Bone Turnover Markers in Postmenopausal Women with Low Bone Mass. J Clin Endocrinol Metab 2011;96(4):972-80. https://doi.org/10.1210/jc.2010-1502
  15. Moran CP, English S, Beringer T, Lindsay JR. Real World Experience of Denosumab Treatment in the Belfast Osteoporosis Service. Ulster Med J 2019;88(3):150-6.
  16. Health Insurance Review & Aseessment Service. Notification 2020-221. Available from https://www.hira.or.kr/bbsDummy.do?pgmid=HIRAA020002000100&brdScnBltNo=4&brdBltNo=8254. Accessed July 11, 2022
  17. Lyu H, Zhao SS, Yoshida K, et al. Delayed denosumab injections and bone mineral density response: An electronic health recordbased study. J Clin Endocrinol Metab 2020;105(5):1435-44. https://doi.org/10.1210/clinem/dgz321
  18. Wong-Pack M, Kalani A, Hordyk J, et al. The effects of noncompliance to Prolia (denosumab) on the changes in bone mineral density: A retrospective review. J Osteoporos 2016;2016:7903128.
  19. Tsvetov G, Amitai O, Shochat T, Shimon I, Akirov A, Diker-Cohen T. Denosumab-induced hypocalcemia in patients with osteoporosis: can you know who will get low? Osteoporos Int 2020;31(4):655-65. https://doi.org/10.1007/s00198-019-05261-7
  20. Body JJ, Bone HG, de Boer RH, et al. Hypocalcaemia in patients with metastatic bone disease treated with denosumab. Eur J Cancer 2015;51(13):1812-21. https://doi.org/10.1016/j.ejca.2015.05.016