Hospital for Special Surgery, New York, NY, USA.
Tufts Medical Center, Boston, MA, USA.
Osteoarthritis Cartilage. 2023 Dec;31(12):1612-1626. doi: 10.1016/j.joca.2023.08.010. Epub 2023 Aug 29.
Due to the risk of rapidly progressive osteoarthritis (RPOA), the phase III studies of subcutaneous (SC) tanezumab in patients with moderate to severe hip or knee osteoarthritis (OA) included comprehensive joint safety surveillance. This pooled analysis summarizes these findings.
Joint safety events in the phase III studies of SC tanezumab (2 placebo- and 1- nonsteroidal anti-inflammatory drug [NSAID]-controlled) were adjudicated by a blinded external committee. Outcomes of RPOA1 and RPOA2, primary osteonecrosis, subchondral insufficiency fracture, and pathological fracture comprised the composite joint safety endpoint (CJSE). Potential patient- and joint-level risk factors for CJSE, RPOA, and total joint replacement (TJR) were explored.
Overall, 145/4541 patients (3.2%) had an adjudicated CJSE (0% placebo; 3.2% tanezumab 2.5 mg; 6.2% tanezumab 5 mg; 1.5% NSAID). There was a dose-dependent risk of adjudicated CJSE, RPOA1, and TJR with tanezumab vs NSAID. Patient-level cross-tabulation found associations between adjudicated RPOA with more severe radiographic/symptomatic (joint pain, swelling, and physical limitation) OA. Risk of adjudicated RPOA1 was highest in patients with Kellgren-Lawrence (KL) grade 2 or 3 OA at baseline. Risk of adjudicated RPOA2 or TJR was highest in patients with KL grade 4 joints at baseline. A higher proportion of joints with adjudicated RPOA2 had a TJR (14/26) than those with adjudicated RPOA1 (16/106).
In placebo- and NSAID controlled studies of SC tanezumab for OA, adjudicated CJSE, RPOA, and TJR most commonly occurred in patients treated with tanezumab and with more severe radiographic or symptomatic OA. NCT02697773; NCT02709486; NCT02528188.
由于存在快速进展性骨关节炎（RPOA）的风险，皮下（SC）注射型 tanezumab 治疗中重度髋或膝关节骨关节炎（OA）的 III 期研究纳入了全面的关节安全性监测。本汇总分析总结了这些发现。
通过盲法外部委员会对 SC tanezumab 的 III 期研究中的关节安全性事件（2 个安慰剂对照和 1 个非甾体抗炎药 [NSAID] 对照）进行裁决。RPOA1 和 RPOA2、原发性骨坏死、软骨下不充分骨折和病理性骨折构成了复合关节安全性终点（CJSE）。探索了 CJSE、RPOA 和全关节置换（TJR）的潜在患者和关节水平风险因素。
总体而言，145/4541 例患者（3.2%）发生了裁决的 CJSE（0%安慰剂；2.5mg tanezumab 组 3.2%；5mg tanezumab 组 6.2%；NSAID 组 1.5%）。与 NSAID 相比，tanezumab 具有剂量依赖性的裁决 CJSE、RPOA1 和 TJR 风险。患者水平交叉表显示，裁决的 RPOA 与更严重的影像学/症状性（关节疼痛、肿胀和身体受限）OA 之间存在关联。基线时 KL 分级 2 或 3 的 OA 患者发生裁决的 RPOA1 风险最高。基线时 KL 分级 4 关节的患者发生裁决的 RPOA2 或 TJR 的风险最高。发生裁决的 RPOA2 的关节中有更高比例（14/26）接受了 TJR，而发生裁决的 RPOA1 的关节中只有 16/106 接受了 TJR。
在 SC tanezumab 治疗 OA 的安慰剂和 NSAID 对照研究中，裁决的 CJSE、RPOA 和 TJR 最常发生在接受 tanezumab 治疗且影像学或症状性 OA 更严重的患者中。NCT02697773；NCT02709486；NCT02528188。
