度洛西汀治疗骨关节炎所致膝关节疼痛患者的疗效：一项日本III期随机研究的探索性事后分析
Response to duloxetine in patients with knee pain due to osteoarthritis: an exploratory post hoc analysis of a Japanese Phase III randomized study.
作者信息
Itoh Naohiro, Tsuji Toshinaga, Ishida Mitsuhiro, Ochiai Toshimitsu, Konno Shinichi, Uchio Yuji
机构信息
Medical Affairs Department, Shionogi & Co. Ltd, Osaka, Japan,
Clinical Development Department, Shionogi & Co. Ltd, Osaka, Japan.
出版信息
J Pain Res. 2018 Oct 26;11:2603-2616. doi: 10.2147/JPR.S176036. eCollection 2018.
PURPOSE
To assess whether patients with knee osteoarthritis pain who have early pain reduction or treatment-related adverse events of special interest (TR-AESIs; constipation, decreased appetite, malaise, nausea, somnolence, thirst) with duloxetine treatment are more likely to have later improvements in pain and quality of life (QOL) relative to placebo than patients without these early indicators.
PATIENTS AND METHODS
This was a post hoc analysis of 14-week randomized trial of Japanese patients with knee osteoarthritis pain (Brief Pain Inventory [BPI]-Severity average pain score ≥4) receiving duloxetine 60 mg/day (n=177 analyzed) or placebo (n=176). Primary trial outcome was change from baseline in BPI-Severity average pain at Week 14. Subgroups included early pain reduction (≥30%, 10%-30%, or <10% decrease in BPI-Severity average pain at Week 4) and early TR-AESIs (with/without TR-AESIs by Week 2). Measures included changes from baseline in BPI-Severity average pain, QOL (BPI-Interference, Western Ontario and McMaster Universities Osteoarthritis Index), Patient Global Impression of Improvement (PGI-I), and response rate (proportion achieving ≥30% or ≥50% pain reduction at Week 14).
RESULTS
The ≥30% early pain reduction subgroup (n=93) had significantly greater improvements in pain, QOL, and PGI-I and higher ≥30% and ≥50% response rates than placebo; the 10%-30% (n=45) and the <10% (n=33) pain reduction subgroups did not show the same (except 10%-30% group: PGI-I at Week 10 and some QOL at Weeks 10 and/or 14). Both TR-AESI subgroups (with, n=52; without, n=125) had significantly greater improvements in pain, PGI-I, and most QOL measures and higher response rates than placebo.
CONCLUSION
Early efficacy responses to duloxetine treatment, but not early TR-AESIs, may predict later pain reduction and QOL improvements in Japanese patients with knee osteoarthritis pain.
CLINICALTRIALSGOV
NCT02248480.
目的
评估与无这些早期指标的患者相比，接受度洛西汀治疗的膝骨关节炎疼痛患者若出现早期疼痛减轻或特殊关注的治疗相关不良事件（TR-AESI；便秘、食欲减退、不适、恶心、嗜睡、口渴），是否更有可能在后期出现疼痛和生活质量（QOL）改善。
患者与方法
这是一项对日本膝骨关节炎疼痛患者（简明疼痛量表[BPI]-严重程度平均疼痛评分≥4）进行的为期14周的随机试验的事后分析，这些患者接受60毫克/天度洛西汀治疗（分析了177例）或安慰剂治疗（176例）。试验的主要结局是第14周时BPI-严重程度平均疼痛较基线的变化。亚组包括早期疼痛减轻（第4周时BPI-严重程度平均疼痛降低≥30%、10%-30%或<10%）和早期TR-AESI（第2周时有/无TR-AESI）。测量指标包括BPI-严重程度平均疼痛、QOL（BPI-干扰、西安大略和麦克马斯特大学骨关节炎指数）、患者总体改善印象（PGI-I）较基线的变化，以及缓解率（第14周时疼痛减轻≥30%或≥50%的比例）。
结果
早期疼痛减轻≥30%的亚组（93例）在疼痛、QOL和PGI-I方面的改善显著大于安慰剂组，且≥30%和≥50%的缓解率更高；疼痛减轻10%-30%（45例）和<10%（33例）的亚组未显示出同样的情况（10%-30%组除外：第10周时的PGI-I以及第10周和/或第14周时的一些QOL）。两个TR-AESI亚组（有，52例；无，125例）在疼痛、PGI-I和大多数QOL测量指标方面的改善显著大于安慰剂组，且缓解率更高。
结论
度洛西汀治疗的早期疗效反应，而非早期TR-AESI，可能预示着日本膝骨关节炎疼痛患者后期疼痛减轻和QOL改善。
临床试验注册
NCT02248480。
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