Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Appalachian Regional Orthopaedic & Sports Medicine, Boone, North Carolina, USA.
Ann Rheum Dis. 2015 Jun;74(6):1202-11. doi: 10.1136/annrheumdis-2013-204905. Epub 2014 Mar 13.
To evaluate whether subjects with knee or hip osteoarthritis (OA) pain on non-steroidal anti-inflammatory drugs (NSAIDs) received greater benefit when tanezumab monotherapy replaced or was coadministered with NSAIDs.
Subjects (N=2700) received intravenous tanezumab (5 or 10 mg) or placebo every 8 weeks with or without oral naproxen 500 mg twice daily or celecoxib 100 mg twice daily. Efficacy was assessed as change from baseline to week 16 in three co-primary endpoints: Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain, WOMAC Physical Function and Patient's Global Assessment (PGA) of OA. Safety assessments included adverse events, physical and neurological examinations, laboratory tests and vital signs.
Although all tanezumab treatments provided significant improvements in WOMAC Pain and Physical Function over either NSAID alone, only tanezumab+NSAIDs were significant versus NSAIDs with PGA and met the prespecified definition of superiority. Combination treatment did not substantially improve pain or function over tanezumab monotherapy. Adverse event frequency was higher with tanezumab than with NSAIDs and highest with combination therapy. Higher incidence of all-cause total joint replacements occurred with tanezumab+NSAID versus tanezumab monotherapy or NSAIDs. Rapidly progressive OA incidence was significantly greater versus NSAID in all tanezumab groups except tanezumab 5 mg monotherapy.
Subjects receiving partial symptomatic relief of OA pain with NSAIDs may receive greater benefit with tanezumab monotherapy. While only coadministration of tanezumab with NSAIDs met the definition of superiority, combination treatment did not provide important benefits over tanezumab monotherapy; small differences in efficacy were negated by treatment-limiting or irreversible safety outcomes.
NCT00809354.
评估膝或髋关节骨关节炎（OA）疼痛患者在使用替扎尼定单药治疗替代或联合非甾体抗炎药（NSAIDs）治疗时，是否能从中获得更大的获益。
受试者（n=2700）接受静脉注射替扎尼定（5 或 10mg）或安慰剂，每 8 周 1 次，同时接受口服萘普生 500mg，每日 2 次或塞来昔布 100mg，每日 2 次。疗效评估指标为从基线到第 16 周的三个主要终点的变化：WOMAC 骨关节炎指数（WOMAC）疼痛、WOMAC 躯体功能和患者对 OA 的总体评估（PGA）。安全性评估包括不良事件、体格和神经检查、实验室检查以及生命体征。
尽管所有替扎尼定治疗方案均能显著改善 WOMAC 疼痛和躯体功能，优于单独使用 NSAIDs，但只有替扎尼定+NSAIDs 与 NSAIDs 相比在 PGA 上有显著改善，符合优效性的预先设定定义。联合治疗并未显著改善疼痛或躯体功能，优于替扎尼定单药治疗。替扎尼定治疗组的不良事件发生率高于 NSAIDs 治疗组，联合治疗组最高。与替扎尼定单药治疗或 NSAIDs 治疗相比，替扎尼定+NSAID 治疗组发生全关节置换术的总发生率更高。除替扎尼定 5mg 单药治疗组外，替扎尼定组所有治疗组的快速进展性 OA 发生率均显著高于 NSAIDs 组。
接受 NSAIDs 治疗能部分缓解 OA 疼痛症状的患者，可能会从替扎尼定单药治疗中获得更大的获益。虽然仅替扎尼定联合 NSAIDs 治疗符合优效性定义，但与替扎尼定单药治疗相比，联合治疗并未提供重要的获益；疗效的微小差异被治疗受限或不可逆转的安全性结果所抵消。
NCT00809354。
