抗 RANKL 抗体治疗伴慢性肾脏病的糖尿病性活动期夏科氏足神经骨关节炎

Anti-RANKL Antibody For Active Charcot Foot Neuro-Osteoarthropathy in Patients with Diabetes and Chronic Kidney Disease.

机构信息

Deptartment of Endocrinology, PGIMER, Chandigarh, India.

Department of Endocrinology, Alchemist Hospitals, Panchkula, India.

出版信息

Foot Ankle Int. 2024 Oct;45(10):1122-1130. doi: 10.1177/10711007241268147. Epub 2024 Aug 26.

DOI:10.1177/10711007241268147

PMID:39188121

Abstract

BACKGROUND

Charcot neuroosteoarthropathy (CNO) is characterized with increased osteoclastic activity that can be curbed with antiresorptive agents. Chronic kidney disease (CKD) precludes bisphosphonates but anti-receptor activator of nuclear factor-B ligand (anti-RANKL) antibody, denosumab, can be contemplated in CKD. We investigated denosumab for active CNO of foot in CKD for CNO remission.

METHODS

During the study period, 446 persons of diabetes with unilateral, active CNO of foot and CKD were identified and 78 were finally enrolled. Patients received either 60 mg denosumab (single-dose, subcutaneous) along with standard of care (SoC) as total contact cast (TCC) (group A; n = 26) or SoC (group B; n = 52) only. Patients were followed every 4 weeks until CNO remission and subsequently every 8 weeks until 48 weeks following remission. Remission was defined as temperature difference <2 °C between 2 feet confirmed twice (4 weeks apart) with clinical resolution of signs of inflammation. The primary outcome studied was proportion of patients achieving remission within 48 weeks and the time to remission.

RESULTS

Median age was 56.5 (48.8-65) and 57 (48.5-61.2) years, = .57; duration of diabetes 16 (10-25.3) and 14.9 (10-19) years, = .151; and estimated glomerular filtration rate 44.8 (21.1-65.6) and 45.7 (32.9-55.7) mL/min/1.73 m, = .771, in group A and B, respectively. Median temperature difference at presentation between the affected and opposite foot was 3.4 °C (2.7-6.9) and 3.2 °C (2.2-4.0), = .119, respectively. All patients achieved remission in group A (100%) compared with 42 (80.8%) in group B ( = .006) (hazard ratio 0.52, 95% CI: 0.32-0.87; = .012). The median time to remission was similar in the 2 groups (15 [11-25] and 17.5 [14-31.5] weeks, = .229, respectively). 25-Hydroxyvitamin D >14 ng/mL was significantly associated (OR 9.5, 95% CI 1.04-87.5, = .045) with remission.

CONCLUSION

Anti-RANKL antibody added to SoC (TCC) induces remission of active foot CNO in greater proportions of patients with diabetes and CKD.

摘要

背景

夏科氏关节病（CNO）的特征是破骨细胞活性增加，可通过抗吸收剂来抑制。慢性肾脏病（CKD）会排除双膦酸盐，但可考虑在 CKD 中使用核因子 κB 配体受体拮抗剂（抗-RANKL）抗体地舒单抗。我们研究了地舒单抗在 CKD 中治疗活动性足部 CNO 以达到 CNO 缓解。

方法

在研究期间，确定了 446 名患有单侧活动性足部 CNO 和 CKD 的糖尿病患者，最终有 78 名患者入组。患者接受 60mg 地舒单抗（单次皮下注射）联合标准治疗（SoC）（TCC）（A 组；n=26）或仅接受 SoC（B 组；n=52）。患者每 4 周接受一次随访，直到 CNO 缓解，随后每 8 周随访一次，直到缓解后 48 周。缓解定义为双脚之间的温差<2°C，且两次确认（相隔 4 周），同时炎症体征临床消退。主要研究结果是在 48 周内达到缓解的患者比例和达到缓解的时间。

结果

A 组和 B 组的中位年龄分别为 56.5（48.8-65）岁和 57（48.5-61.2）岁， = .57；糖尿病病程分别为 16（10-25.3）年和 14.9（10-19）年， = .151；估算肾小球滤过率分别为 44.8（21.1-65.6）和 45.7（32.9-55.7）mL/min/1.73 m， = .771。A 组和 B 组中，就诊时受累侧与对侧足部的平均温差分别为 3.4°C（2.7-6.9）和 3.2°C（2.2-4.0）， = .119。A 组所有患者均达到缓解（100%），而 B 组仅 42 例（80.8%）达到缓解（ = .006）（风险比 0.52，95%CI：0.32-0.87； = .012）。两组达到缓解的中位时间相似（15 [11-25]周和 17.5 [14-31.5]周， = .229）。25-羟维生素 D >14ng/mL 与缓解显著相关（OR 9.5，95%CI 1.04-87.5， = .045）。