骨关节炎疼痛的膝关节或髋关节患者III期临床试验亚组分析中他尼珠单抗疗效和安全性的汇总分析。
Pooled analysis of tanezumab efficacy and safety with subgroup analyses of phase III clinical trials in patients with osteoarthritis pain of the knee or hip.
作者信息
Tive Leslie, Bello Alfonso E, Radin David, Schnitzer Thomas J, Nguyen Ha, Brown Mark T, West Christine R
机构信息
Pfizer Inc, New York, NY, USA,
Illinois Bone and Joint Institute, Glenview, IL, USA.
出版信息
J Pain Res. 2019 Mar 19;12:975-995. doi: 10.2147/JPR.S191297. eCollection 2019.
PURPOSE
A pooled analysis was conducted to evaluate tanezumab efficacy and safety in patients with osteoarthritis (OA), including subgroup analyses of at-risk patients with diabetes, severe OA symptoms, and those aged ≥65 years.
PATIENTS AND METHODS
Data from phase III placebo-controlled clinical trials of patients with moderate-to-severe OA of the knee or hip were pooled to evaluate tanezumab efficacy (four trials) and safety (nine trials). Patients received intravenous tanezumab, tanezumab plus an oral NSAID (naproxen, celecoxib, or diclofenac), active comparator (naproxen, celecoxib, diclofenac, or oxycodone), or placebo. Efficacy assessments included change from baseline to week 16 in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and physical function scores, Patient's Global Assessment (PGA) of OA, and percentage of patients with ≥30%, ≥50%, ≥70%, and ≥90% improvement in WOMAC pain. Safety assessments included adverse event (AE) documentation and physical and neurologic examinations.
RESULTS
Tanezumab significantly improved all efficacy end points in the overall population. Efficacy in at-risk patient subgroups was similar to the overall population. Incidence of AEs was highest in the tanezumab plus NSAID group and lowest in the placebo group. Incidence of AEs in the tanezumab monotherapy and active comparator groups was similar. Overall incidence of AEs was similar across subgroups. AEs of abnormal peripheral sensation were more frequently reported in tanezumab-treated patients compared with placebo or active comparator. Patients receiving active comparator had a slightly higher incidence of AEs suggestive of postganglionic sympathetic dysfunction.
CONCLUSION
Tanezumab consistently provided significant improvement of pain, physical function, and PGA in individuals with OA, including patients with diabetes, severe OA symptoms, or aged ≥65 years. No increased safety risk was observed in at-risk patient subgroups.
TRIAL REGISTRATION
NCT00733902, NCT00744471, NCT00830063, NCT00863304, NCT00809354, NCT00864097, NCT00863772, NCT01089725, NCT00985621.
目的
进行一项汇总分析，以评估他尼珠单抗在骨关节炎（OA）患者中的疗效和安全性，包括对糖尿病高危患者、有严重OA症状的患者以及年龄≥65岁患者的亚组分析。
患者与方法
汇总膝关节或髋关节中重度OA患者的III期安慰剂对照临床试验数据，以评估他尼珠单抗的疗效（四项试验）和安全性（九项试验）。患者接受静脉注射他尼珠单抗、他尼珠单抗加口服非甾体抗炎药（萘普生、塞来昔布或双氯芬酸）、活性对照药（萘普生、塞来昔布、双氯芬酸或羟考酮）或安慰剂。疗效评估包括从基线到第16周的西安大略和麦克马斯特大学骨关节炎指数（WOMAC）疼痛和身体功能评分变化、OA患者的整体评估（PGA）以及WOMAC疼痛改善≥30%、≥50%、≥70%和≥90%的患者百分比。安全性评估包括不良事件（AE）记录以及体格和神经学检查。
结果
他尼珠单抗在总体人群中显著改善了所有疗效终点。高危患者亚组的疗效与总体人群相似。不良事件发生率在他尼珠单抗加非甾体抗炎药组中最高，在安慰剂组中最低。他尼珠单抗单药治疗组和活性对照药组的不良事件发生率相似。各亚组的不良事件总体发生率相似。与安慰剂或活性对照药相比，接受他尼珠单抗治疗的患者更频繁报告外周感觉异常的不良事件。接受活性对照药治疗的患者出现提示节后交感神经功能障碍的不良事件发生率略高。
结论
他尼珠单抗持续显著改善OA患者的疼痛、身体功能和PGA，包括糖尿病患者、有严重OA症状的患者或年龄≥65岁的患者。在高危患者亚组中未观察到安全性风险增加。
试验注册
NCT00733902、NCT00744471、NCT00830063、NCT00863304、NCT00809354、NCT00864097、NCT00863772、NCT01089725、NCT00985621。
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