Kivitz Alan J, Conaghan Philip G, Cinar Amy, Lufkin Joelle, Kelley Scott D
Altoona Center for Clinical Research, Duncansville, PA, USA.
Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds and Leeds Biomedical Research Centre, Leeds Teaching Hospitals NHS Trust, Leeds, UK.
Pain Ther. 2019 Dec;8(2):271-280. doi: 10.1007/s40122-019-0125-1. Epub 2019 May 7.
INTRODUCTION: In clinical trials for knee osteoarthritis (OAK), rescue medication is commonly provided to manage uncontrolled index-knee pain. The impact of treatment on rescue medication utilization provides important information on the robustness of analgesic effect. In randomized controlled OAK trials (NCT01487161, NCT02116972, NCT02357459), intra-articular (IA) triamcinolone acetonide extended-release (TA-ER) demonstrated substantial, prolonged analgesia versus saline-placebo and TA crystalline solution (TAcs) as assessed by patient-reported pain scales. This pooled analysis assessed the impact of TA-ER on rescue medication use. METHODS: Patients (N = 798) with OAK (American College of Rheumatology criteria; Kellgren-Lawrence grade 2/3) and baseline average daily pain intensity score ≥ 5 to ≤ 9 (0-10 numeric rating scale) received a single IA injection of TA-ER (N = 324), saline-placebo (N = 262), or TAcs (N = 212). Acetaminophen/paracetamol tablets were provided to treat uncontrolled pain (knee or otherwise). Rescue medication consumption was monitored through a daily diary; pill counts were confirmed at the clinical site. Differences in rescue medication use were measured by least-squares mean (LSM) differences, number of rescue medication tablets used per day, and in area under the effect (AUE) curves of rescue medication tablets used per week. RESULTS: The overall number of rescue medication tablets used per day through week 24 was significantly less (p ≤ 0.05) for TA-ER versus saline-placebo (LSM difference, - 0.43) and TAcs (- 0.24). Rescue medication use was significantly (p ≤ 0.05) lower following TA-ER versus saline-placebo across weeks 1-12 (AUE; LSM difference, - 24.5) and weeks 1-24 (AUE; - 51.6) and versus TAcs across weeks 1-12 (AUE; - 21.1). CONCLUSIONS: In patients with painful OAK, reduced rescue medication use may be a potential benefit of TA-ER and further supports its analgesic efficacy. Additional research is needed to assess whether TA-ER impacts the use of other common oral analgesics (nonsteroidal anti-inflammatory drugs, opioids) for patients with OAK. FUNDING: Flexion Therapeutics, Inc., Burlington, MA, USA. Plain language summary available for this article.
引言：在膝骨关节炎（OAK）的临床试验中，通常会提供急救药物来处理未得到控制的膝关节疼痛。治疗对急救药物使用的影响为镇痛效果的稳健性提供了重要信息。在随机对照的OAK试验（NCT01487161、NCT02116972、NCT02357459）中，与生理盐水安慰剂和曲安奈德结晶溶液（TAcs）相比，关节内（IA）注射长效曲安奈德（TA-ER）通过患者报告的疼痛量表评估显示出显著且持久的镇痛效果。这项汇总分析评估了TA-ER对急救药物使用的影响。 方法：患有OAK（美国风湿病学会标准；Kellgren-Lawrence分级2/3级）且基线平均每日疼痛强度评分≥5至≤9（0-10数字评分量表）的患者（N = 798）接受单次IA注射TA-ER（N = 324）、生理盐水安慰剂（N = 262）或TAcs（N = 212）。提供对乙酰氨基酚/扑热息痛片以治疗未得到控制的疼痛（膝关节或其他部位）。通过每日日记监测急救药物的消耗情况；在临床研究点确认药片计数。通过最小二乘均值（LSM）差异、每日使用的急救药物片数以及每周使用的急救药物片数的效应曲线下面积（AUE）来衡量急救药物使用的差异。 结果：在第24周之前，TA-ER组每日使用的急救药物总片数显著少于生理盐水安慰剂组（LSM差异，-0.43）和TAcs组（-0.24）（p≤0.05）。在第1至12周（AUE；LSM差异，-24.5）和第1至24周（AUE；-51.6），TA-ER组的急救药物使用量显著低于生理盐水安慰剂组（p≤0.05），在第1至12周（AUE；-21.1），TA-ER组的急救药物使用量显著低于TAcs组。 结论：在患有疼痛性OAK的患者中，减少急救药物的使用可能是TA-ER的一个潜在益处，并进一步支持其镇痛效果。需要进行更多研究来评估TA-ER是否会影响OAK患者对其他常见口服镇痛药（非甾体抗炎药、阿片类药物）的使用。 资助：美国马萨诸塞州伯灵顿的Flexion Therapeutics公司。本文提供了通俗易懂的摘要。
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