Yataba Ikuko, Otsuka Noboru, Matsushita Isao, Matsumoto Hideo, Hoshino Yuichi
Taisho Pharmaceutical Co, Ltd.
Institute for Integrated Sports Medicine, School of Medicine, Keio University, Tokyo.
J Pain Res. 2017 Apr 11;10:867-880. doi: 10.2147/JPR.S131779. eCollection 2017.
Nonsteroidal anti-inflammatory drug (NSAID) patches are convenient for use and show much less gastrointestinal side effects than oral NSAIDs, whereas its percutaneous absorption is not sufficient for the expression of clinical efficacy at satisfactory level. S-flurbiprofen plaster (SFPP) has shown dramatic improvement in percutaneous absorption results from animal and clinical studies. In this study, the efficacy and safety of SFPP were compared with placebo in patients with knee osteoarthritis (OA) to determine its optimal dose. This was a multicenter, randomized, double-blind, parallel-group comparative study.
Enrolled 509 knee OA patients were treated with placebo or SFPP at 10, 20, or 40 mg applied on the affected site once daily for 2 weeks. The primary endpoint for efficacy was improvement in knee pain on rising from the chair assessed by visual analog scale (VAS). The other endpoints were clinical symptoms, pain on walking, and global assessment by both investigator and patient. Safety was evaluated by observing adverse events (AEs).
VAS change in knee pain from baseline to trial end was dose-dependent, least squares mean was 29.5, 31.5, 32.0, and 35.6 mm in placebo and SFPP 10, 20, and 40 mg, respectively. A significant difference was observed between placebo and SFPP 40 mg (=0.001). In contrast, the effect of SFPP at a dose ≤20 mg was not significantly different from that of placebo. The proportion of the patients who achieved 50% pain relief was 72.4% in 40 mg and 51.2% in placebo (<0.001). In all other endpoints, SFPP 40 mg showed significant improvement compared with placebo. The incidence of AEs was not different across all four groups, and no severe AEs were observed.
Clinically relevant pain relief was observed in all groups including placebo. Especially 40 mg showed remarkable pain relief in not only primary endpoint but also all the other endpoint with significant differences over placebo. The safety profile of SFPP 40 mg was not different from that of placebo. Therefore, 40 mg was determined as the optimal tested dose.
非甾体抗炎药（NSAID）贴剂使用方便，与口服NSAIDs相比，胃肠道副作用少得多，但其经皮吸收不足以达到令人满意的临床疗效。S-氟比洛芬贴剂（SFPP）在动物和临床研究中显示出经皮吸收有显著改善。在本研究中，将SFPP与安慰剂在膝骨关节炎（OA）患者中进行疗效和安全性比较，以确定其最佳剂量。这是一项多中心、随机、双盲、平行组对照研究。
纳入509例膝OA患者，分别接受安慰剂或10、20或40mg的SFPP治疗，每日一次，涂抹于患部，持续2周。疗效的主要终点是通过视觉模拟量表（VAS）评估从椅子上起身时膝关节疼痛的改善情况。其他终点包括临床症状、行走时的疼痛以及研究者和患者的整体评估。通过观察不良事件（AE）评估安全性。
从基线到试验结束时膝关节疼痛的VAS变化呈剂量依赖性，安慰剂组以及SFPP 10、20和40mg组的最小二乘均值分别为29.5、31.5、32.0和35.6mm。安慰剂组与SFPP 40mg组之间观察到显著差异（P = 0.001）。相比之下，剂量≤20mg的SFPP与安慰剂的效果无显著差异。疼痛缓解50%的患者比例在40mg SFPP组为72.4%，在安慰剂组为51.2%（P < 0.001）。在所有其他终点，40mg SFPP组与安慰剂组相比均有显著改善。四组的AE发生率无差异，未观察到严重AE。
所有组包括安慰剂组均观察到具有临床意义的疼痛缓解。特别是40mg剂量不仅在主要终点，而且在所有其他终点均显示出显著的疼痛缓解，与安慰剂组有显著差异。40mg SFPP的安全性与安慰剂无异。因此，40mg被确定为最佳测试剂量。
