Birbara Charles, Dabezies Eugene J, Burr Aimee M, Fountaine Robert J, Smith Michael D, Brown Mark T, West Christine R, Arends Rosalin H, Verburg Kenneth M
Department of Medicine, University of Massachusetts School of Medicine, Worcester, MA.
Pensacola Research Consultants, Pensacola, FL.
J Pain Res. 2018 Jan 8;11:151-164. doi: 10.2147/JPR.S135257. eCollection 2018.
BACKGROUND/OBJECTIVE: The objective of this study was to investigate the safety and efficacy of subcutaneous (SC) and intravenous (IV) tanezumab administration in osteoarthritis (OA) patients.
Study 1027 (NCT01089725), a placebo-controlled trial, evaluated the efficacy of SC tanezumab (ie, 2.5, 5, and 10 mg) and the therapeutic equivalence of 10 mg tanezumab given subcutaneously versus intravenously every 8 weeks in the symptomatic treatment of OA. Coprimary endpoints were: change from baseline in Western Ontario and McMaster Universities Osteoarthritis index (WOMAC) Pain and Physical Function indices, and Patient's Global Assessment (PGA) of OA. Study 1043 (NCT00994890) was a long-term, noncontrolled safety study of tanezumab (ie, 2.5, 5, and 10 mg) subcutaneously administered every 8 weeks. Both studies were discontinued prematurely due to a US Food and Drug Administration partial clinical hold.
Due to the clinical hold, Study 1027 was underpowered, and no statistical analyses were performed. Mean (standard error [SE]) change from baseline to week 8 in WOMAC Pain in tanezumab groups ranged from -3.59 (0.26) to -3.89 (0.32), versus -2.74 (0.25) with placebo. Mean (SE) change from baseline to week 8 in WOMAC Physical Function ranged from -3.13 (0.25) to -3.51 (0.28) with tanezumab and was -2.26 (0.24) with placebo. PGA mean (SE) change from baseline to week 8 ranged from -0.90 (0.11) to -1.08 (0.12) with tanezumab and was -0.78 (0.10) with placebo. Similar effectiveness was associated with tanezumab in Study 1043. Few patients in either study (1.4%-5.2%) discontinued due to adverse events. Five patients required total joint replacements in Study 1027 (placebo, n=2 [2.8%]; tanezumab 2.5 mg, n=3 [4.1%]) and 34 patients in Study 1043 (tanezumab 2.5 mg, n=11 [4.8%]; tanezumab 5 mg, n=8 [3.6%]; tanezumab 10 mg, n=15 [6.6%]).
Preliminary results show similar efficacy and safety for both SC and IV administration of tanezumab based on the direct comparisons reported here and indirect comparisons with published results, confirming pharmacokinetic/pharmacodynamic modeling predictions.
背景/目的：本研究的目的是调查皮下注射（SC）和静脉注射（IV）坦尼单抗治疗骨关节炎（OA）患者的安全性和有效性。
研究1027（NCT01089725）是一项安慰剂对照试验，评估皮下注射坦尼单抗（即2.5、5和10毫克）的疗效，以及每8周皮下注射与静脉注射10毫克坦尼单抗在OA症状治疗中的治疗等效性。共同主要终点为：西安大略和麦克马斯特大学骨关节炎指数（WOMAC）疼痛和身体功能指数相对于基线的变化，以及患者对OA的整体评估（PGA）。研究1043（NCT00994890）是一项对每8周皮下注射坦尼单抗（即2.5、5和10毫克）进行的长期非对照安全性研究。两项研究均因美国食品药品监督管理局的部分临床暂停而提前终止。
由于临床暂停，研究1027的样本量不足，未进行统计分析。坦尼单抗组从基线到第8周WOMAC疼痛的平均（标准误差[SE]）变化范围为-3.59（0.26）至-3.89（0.32），而安慰剂组为-2.74（0.25）。坦尼单抗组从基线到第8周WOMAC身体功能的平均（SE）变化范围为-3.13（0.25）至-3.51（0.28），安慰剂组为-2.26（0.24）。坦尼单抗组从基线到第8周PGA的平均（SE）变化范围为-0.90（0.11）至-1.08（0.12），安慰剂组为-0.78（0.10）。研究1043中坦尼单抗的有效性相似。两项研究中很少有患者（1.4%-5.2%）因不良事件停药。研究1027中有5名患者需要进行全关节置换（安慰剂组，n = 2 [2.8%]；坦尼单抗2.5毫克组，n = 3 [4.1%]），研究1043中有34名患者（坦尼单抗2.5毫克组，n = 11 [4.8%]；坦尼单抗5毫克组，n = 8 [3.6%]；坦尼单抗10毫克组，n = 15 [6.6%]）。
根据本研究报告的直接比较以及与已发表结果的间接比较，初步结果显示皮下注射和静脉注射坦尼单抗的疗效和安全性相似，证实了药代动力学/药效学模型预测。
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