デノスマブは、主に多発性骨髄腫及び固形癌骨転移による骨病変に対して効能・効果を有する抗 RANKLモノクローナル抗体製剤である。デノスマブは通常、副作用として起こり得る低カルシウム(以下、Ca)血症を予防する目的でCa製剤を併用することが推奨されている。一方で治療経過中にデノスマブが中止されているにも関わらず、Ca製剤が継続処方されている事例が散見されている。デノスマブ中止期間中のCa製剤の継続可否が患者に与える影響に関しては、十分な報告がなされていない。本研究は、デノスマブ中止後のCa製剤の継続有無による血清Ca値を含めた患者の経過を調査し、Ca製剤の適正使用に向けた運用を検討する。なお、研究開始前に倫理審査委員会により承認を受けた。
調査期間は2017年4月〜2020年3月の3年間、診療録を用いた後ろ向き調査を行った。主要評価項目は、デノスマブ中止後にCa製剤を継続処方された患者における補正Ca値の経時的変化とした。
デノスマブによる治療を途中で中止した患者155名のうち、デノスマブ中止後もCa製剤を継続服用していた患者は66名であった。デノスマブを中止した時点およびその後にCa製剤を中止した時点における補正Ca値2点の平均値を比較した結果、前者は9.40mg/dL、後者は9.49mg/dLであり、有意な差は見られなかった（p=0.339）。また、診療科別でも同様の比較を行ったが、補正Ca値の変化に有意な差は見られなかった。
以上により、デノスマブ中止後のCa製剤の継続服用が直ちにCa値上昇に影響するわけではないと考えられるが、Ca値は患者の併用薬剤や病状の進行等によって増減の影響を受ける可能性があるため、更なる精査を検討する。また、Ca製剤の適正使用という観点より、デノスマブ中止時にCa製剤も休薬することは、患者の内服負担軽減に貢献できると考えられる。このため、今後はデノスマブ中止と同時にCa製剤を中止した患者の補正Ca値を調査するにより、Ca製剤服用の必要性に関する更なる検討を進めていく予定である。
Denosumab is an anti-RANKL monoclonal antibody preparation that is mainly effective against bone lesions caused by multiple myeloma or solid cancer bone metastasis. Denosumab is usually recommended to be used in combination with calcium (hereinafter referred to as Ca) preparations to prevent hypocalcemia, which may occur as a side effect. On the other hand, there are some cases in which Ca preparations are continuously prescribed even though denosumab has been discontinued during the course of treatment. Sufficient reports have not been made on the effect of continuation of Ca preparations on patients during the denosumab discontinuation period. In this study, we will investigate the course of patients including serum Ca levels depending on whether or not Ca preparations are continued after denosumab discontinuation, and examine the operation for proper use of Ca preparations. Approval was obtained by the Ethics Review Committee before the start of the study. The survey period was from April 2017 to March 2020, and a retrospective survey was conducted using medical records. The primary endpoint was the time course of corrected Ca levels in patients who were continuously prescribed Ca after discontinuation of denosumab.
Of the 155 patients who discontinued treatment with denosumab, 66 patients continued to take Ca preparations even after discontinuation of denosumab. As a result of comparing the average values of the two corrected Ca values at the time when denosumab was discontinued and when the Ca preparation was discontinued thereafter, the former was 9.40 mg / dL and the latter was 9.49 mg / dL, not showing a significant difference (p = 0.339). Similar comparisons were made for each clinical department, but no significant difference was found in the change in the corrected Ca value. Based on the above, it is considered that continuous administration of Ca preparations after discontinuation of denosumab does not immediately affect the increase in Ca level, but the Ca level may be affected by the increase or decrease depending on the patient's concomitant drug and the progression of the medical condition. Therefore, further scrutiny will be considered. In addition, from the viewpoint of proper use of Ca preparations, it is considered that withdrawal of Ca preparations when denosumab is discontinued can contribute to reducing the burden of oral administration on patients. Therefore, in the future, we plan to further investigate the necessity of taking Ca preparations by investigating the corrected Ca value of patients who discontinued Ca preparations at the same time as denosumab discontinuation.