Kivitz Alan, Kwong Louis, Shlotzhauer Tammi, Lufkin Joelle, Cinar Amy, Kelley Scott
Altoona Center for Clinical Research, Duncansville, 175 Meadowbrook Lane, PO Box 1018, Duncansville, PA 16635, USA.
Department of Orthopaedic Surgery, Harbor-UCLA Medical Center, Torrance, CA, USA.
Ther Adv Musculoskelet Dis. 2019 Oct 16;11:1759720X19881309. doi: 10.1177/1759720X19881309. eCollection 2019.
Intra-articular corticosteroids are commonly used for pain relief in patients with knee osteoarthritis. Simultaneous intra-articular corticosteroid (CS) knee injections may be beneficial for the ~80-90% of patients who present with, or develop, bilateral knee osteoarthritis, but concurrent injections may increase systemic CS exposure and data on safety/tolerability are lacking. Triamcinolone acetonide extended release (TA-ER) has shown decreased systemic triamcinolone acetonide exposure compared with traditional triamcinolone acetonide crystalline suspension (TAcs) after a single knee injection in patients with knee osteoarthritis. This phase IIa study was designed to assess the safety and systemic triamcinolone acetonide exposure following injections of TA-ER or TAcs into each knee of patients with bilateral knee osteoarthritis.
Patients (⩾40 years) meeting American College of Rheumatology criteria for knee osteoarthritis in both knees received concurrent single intra-articular injections of TA-ER 32 mg or TAcs 40 mg into each knee (total: 64 mg and 80 mg, respectively) and were followed for 6 weeks. Safety was evaluated based on treatment-emergent adverse events (TEAEs). Blood samples for pharmacokinetic analysis were collected pre-injection, and at the following postinjection time points: 1, 2, 3, 4, 5, 6, 8, 10, 12, and 24 h, and days 8, 15, 29, and 43.
Baseline characteristics were balanced between patients randomly assigned to TA-ER ( = 12) or TAcs ( = 12). Both treatments were well tolerated with comparable TEAE profiles. Peak plasma triamcinolone acetonide concentrations (C) were lower following bilateral TA-ER injections [geometric mean, 2277.7 pg/ml (95% CI, 1602.13-3238.04)] compared with bilateral TAcs injections [7394.7 pg/ml (2201.06-24,843.43)], with median times to C (T) of 4.5 and 6.5 h, respectively.
In patients with bilateral knee osteoarthritis, intra-articular injection of TA-ER into both knees was well tolerated. Consistent with pharmacokinetic profiles observed after a single knee injection, plasma triamcinolone acetonide concentrations were lower after bilateral TA-ER injections compared with the higher and more variable concentrations observed after bilateral TAcs injections.
NCT03378076.
关节内注射皮质类固醇常用于缓解膝关节骨关节炎患者的疼痛。对于约80% - 90%出现双侧膝关节骨关节炎或病情发展为双侧膝关节骨关节炎的患者，同时进行双侧关节内皮质类固醇（CS）膝关节注射可能有益，但同时注射可能会增加全身CS暴露量，且缺乏安全性/耐受性数据。与传统的曲安奈德结晶混悬液（TAcs）相比，在膝关节骨关节炎患者单膝注射后，曲安奈德缓释剂（TA - ER）已显示出全身曲安奈德暴露量降低。这项IIa期研究旨在评估在双侧膝关节骨关节炎患者的双膝分别注射TA - ER或TAcs后的安全性和全身曲安奈德暴露量。
符合美国风湿病学会双膝膝关节骨关节炎标准的患者（年龄≥40岁），双膝同时接受单关节内注射TA - ER 32mg或TAcs 40mg（总量分别为64mg和80mg），并随访6周。基于治疗中出现的不良事件（TEAE）评估安全性。在注射前以及注射后以下时间点采集用于药代动力学分析的血样：1、2、3、4、5、6、8、10、12和24小时，以及第8、15、29和43天。
随机分配至TA - ER组（n = 12）或TAcs组（n = 12）的患者基线特征均衡。两种治疗耐受性良好，TEAE情况相当。与双侧TAcs注射[7394.7 pg/ml（2201.06 - 24,843.43）]相比，双侧TA - ER注射后的血浆曲安奈德峰值浓度（C）较低[几何均值，2277.7 pg/ml（95%CI，1602.13 - 3238.04）]，C的中位达峰时间（T）分别为4.5小时和6.5小时。
在双侧膝关节骨关节炎患者中，双膝关节内注射TA - ER耐受性良好。与单膝注射后观察到的药代动力学特征一致，双侧TA - ER注射后的血浆曲安奈德浓度低于双侧TAcs注射后观察到的更高且更具变异性的浓度。
NCT03378076
