University of Maryland School of Medicine, Baltimore.
Hospital for Special Surgery, New York, New York.
Arthritis Rheumatol. 2021 Jul;73(7):1167-1177. doi: 10.1002/art.41674. Epub 2021 Jun 7.
To assess the long-term safety and 16-week efficacy of subcutaneous tanezumab in patients with hip or knee osteoarthritis (OA).
This was a phase III randomized, double-blind, active treatment-controlled (using nonsteroidal antiinflammatory drugs [NSAIDs] as the active treatment control) safety trial of tanezumab (56-week treatment/24-week posttreatment follow-up) in adults who were receiving stable-dose NSAID therapy at the time of screening and who had Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and physical function scores of ≥5; patient global assessment (PtGA) of OA of fair, poor, or very poor; history of inadequate pain relief with standard analgesics; and no history or radiographic evidence of prespecified bone/joint conditions beyond OA. Patients received oral naproxen, celecoxib, or diclofenac twice daily (NSAID group; n = 996) or tanezumab 2.5 mg (n = 1,002) or 5 mg (n = 998) subcutaneously every 8 weeks. Coprimary efficacy end points at week 16 were changes in WOMAC pain and physical function scores and changes in PtGA. The primary joint safety end point over 80 weeks comprised adjudicated rapidly progressive OA type 1 or 2, primary osteonecrosis, subchondral insufficiency fracture, or pathologic fracture. Mean values, least squares mean values, and least squares mean differences between groups (with 95% confidence intervals [95% CIs]) were calculated.
Of 3,021 randomized patients, 2,996 received ≥1 treatment dose. Adverse events (AEs) were similar between patients treated with tanezumab 2.5 mg and those treated with NSAIDs, and were more prevalent in those treated with tanezumab 5 mg. Composite joint safety events were significantly more prevalent with tanezumab 2.5 mg and tanezumab 5 mg than with NSAIDs (observation time-adjusted rate/1,000 patient-years 38.3 [95% CI 28.0, 52.5] and 71.5 [95% CI 56.7, 90.2], respectively, versus 14.8 [95% CI 8.9, 24.6]; P = 0.001 for tanezumab 2.5 mg versus NSAIDs; P < 0.001 for tanezumab 5 mg versus NSAIDs). Tanezumab 5 mg significantly improved pain and physical function but did not improve PtGA at week 16 when compared to NSAIDs; corresponding differences between the tanezumab 2.5 mg and NSAID groups were not statistically significant.
In patients previously receiving a stable dose of NSAIDs, tanezumab administered subcutaneously resulted in more joint safety events than continued NSAIDs, with differences being dose dependent. Pain and physical function improved with both doses of tanezumab compared to NSAIDs, reaching statistical significance with tanezumab 5 mg at 16 weeks.
评估皮下注射特立帕肽治疗髋或膝关节骨关节炎（OA）患者的长期安全性和 16 周疗效。
这是一项特立帕肽的 III 期随机、双盲、活性药物对照（使用非甾体抗炎药 [NSAIDs] 作为活性药物对照）安全性试验，纳入了正在接受稳定剂量 NSAID 治疗且在筛选时 Western Ontario 和 McMaster 大学骨关节炎指数（WOMAC）疼痛和身体功能评分≥5 的成年人；患者整体评估（PtGA）为 OA 中度、差或极差；有标准镇痛药治疗效果不佳的疼痛史；且无预先指定的骨/关节疾病（除 OA 外）的病史或影像学证据。患者接受口服萘普生、塞来昔布或双氯芬酸，每日 2 次（NSAID 组；n=996）或皮下注射特立帕肽 2.5mg（n=1002）或 5mg（n=998），每 8 周 1 次。第 16 周的主要疗效终点为 WOMAC 疼痛和身体功能评分的变化和 PtGA 的变化。80 周时的主要关节安全性终点包括经裁决的快速进展性 OA 1 型或 2 型、原发性骨坏死、软骨下不全骨折或病理性骨折。计算了各组的平均值、最小二乘均值和组间最小二乘均值差异（95%置信区间 [95%CI]）。
在 3021 名随机患者中，2996 名患者接受了至少 1 次治疗剂量。特立帕肽 2.5mg 组和 NSAIDs 组的不良事件（AE）相似，且特立帕肽 5mg 组的 AE 更为常见。特立帕肽 2.5mg 和 5mg 组的复合关节安全性事件发生率明显高于 NSAIDs 组（观察时间调整后的发生率/1000 患者年分别为 38.3 [95%CI 28.0, 52.5]和 71.5 [95%CI 56.7, 90.2]，而 NSAIDs 组为 14.8 [95%CI 8.9, 24.6]；特立帕肽 2.5mg 与 NSAIDs 相比，P=0.001；特立帕肽 5mg 与 NSAIDs 相比，P<0.001）。与 NSAIDs 相比，特立帕肽 5mg 可显著改善疼痛和身体功能，但在第 16 周时对 PtGA 无改善；特立帕肽 2.5mg 组与 NSAIDs 组之间的相应差异无统计学意义。
在先前接受 NSAIDs 稳定剂量治疗的患者中，与继续使用 NSAIDs 相比，皮下注射特立帕肽导致更多的关节安全性事件，且差异与剂量相关。与 NSAIDs 相比，两种剂量的特立帕肽均能改善疼痛和身体功能，特立帕肽 5mg 在第 16 周时达到统计学意义。
