慢性腎臟病第五期病人使用Denosumab之安全性評估：病例系列研究

Safety of Denosumab in Patients With Chronic Kidney Disease Stage 5: A Case Series Study

蘇純儀(Chun-Yi Su) ； 林麗梅(Li-Mei Lin) ； 陳玉瑩(Yuk-Ying Chan) ； 陳惠玉(Hui-Yu Chen) ； 許恆榮(Heng-Jung Hsu)

《臺灣臨床藥學雜誌》 27卷1期 (2019/01) Pp. 37-47

https://doi.org/10.6168/FJCP.201901_27(1).0006

摘要

目的：Denosumab核准適應症為治療有骨折高風險性之停經後婦女及男性骨質疏鬆症，腎功能不全患者不需調整劑量。然而，施打denosumab後，慢性腎臟病第五期病人為發生低血鈣的高風險族群。本研究為探討denosumab使用於此特殊病人其低血鈣發生率及臨床耐受性。方法：使用回溯性之病例系列研究方式，納入於2012年7月至2016年10月期間，曾接受denosumab 60 mg治療之慢性腎臟病第五期病人。採病歷回顧方式，收集基本資料、抽血檢驗數據、denosumab施打劑數、監測低血鈣不良反應及相關併用藥品。結果：收錄病人共28位，平均年齡為73.5 ± 8.8歲，女性有23位(82.1%)。處方denosumab之科別多為骨科 (75.0%)，14位病人施打次數超過1劑，僅有3位病人施打超過4劑的denosumab。總計有13位病人發生低血鈣，首次施打藥物後，發生低血鈣平均天數為27.9 ± 13.4天（範圍10～56天）；6位病人繼續施打denosumab，其中有2位仍再次出現低血鈣。有3位病人出現嚴重症狀性低血鈣，需住院接受靜脈注射鈣製劑治療。結論：本病例系列研究發現慢性腎臟病第五期病人施打denosumab後，低血鈣發生率為46.4%。照護病人之腎臟科醫師應知悉此用藥資訊。未來仍需有更進一步的研究證據，以確認施打denosumab後，造成低血鈣的風險因素，並提供有效的策略以提升用藥安全性。

關鍵字

Denosumab ； 慢性腎臟病第五期 ； 低血鈣 ； 安全性

並列摘要

Objective: Denosumab is indicated to treat osteoporosis in postmenopausal women and men at high risk of fracture. No dose adjustment is necessary in patients with renal impairment. However, hypocalcemia following denosumab administration is a significant risk in patients with chronic kidney disease (CKD) stage 5. The purpose of this study was to evaluate the rate of hypocalcemia and tolerability of this drug in this particular subset of patients. Methods: A retrospective case series study was performed in CKD stage 5 patients who were treated with denosumab 60 mg between July 2012 and October 2016. Patient demographics, laboratory data, number of denosumab doses, episodes of hypocalcemia, and relevant medications were obtained by patient chart review. Results: A total of 28 patients were analyzed. The mean age was 73.5 ± 8.8 years, and 23 patients (82.1%) were women. Denosumab was most commonly prescribed in the Department of Orthopedics (75.0%). Fourteen patients received more than one dose, and only three patients received more than four doses. Thirteen patients had hypocalcemia, and the time to serum calcium nadir was 27.9 ± 13.4 days (range 10-56 days). Six patients received subsequent doses, and two patients experienced repeated hypocalcemic events. Three patients were documented as having severe symptomatic hypocalcemia and were hospitalized for intravenous calcium replacement. Conclusions: This case series study showed that the rate of hypocalcemia was 46.4% in CKD stage 5 patients. Nephrologists must be aware of the initiation of denosumab therapy. Additional research is needed to identify the risk factors of hypocalcemia and effective strategies for improving safety.

並列關鍵字

Denosumab ； Chronic Kidney Disease Stage 5 ； Hypocalcemia ； Safety