Department of Orthopedics and Orthopedic Surgery, Southcoast Health Systems, 300 A Faunce Corner Road, Dartmouth, MA, 02747, USA.
Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds and NIHR Leeds Biomedical Research Centre, Leeds, UK.
Adv Ther. 2019 Jun;36(6):1398-1411. doi: 10.1007/s12325-019-00944-3. Epub 2019 Apr 9.
Osteoarthritis (OA) is common and its prevalence is increased in military service members. In a phase 3 randomized controlled trial (NCT02357459), a single intra-articular injection of an extended-release formulation of triamcinolone acetonide (TA-ER) in participants with unilateral or bilateral knee OA demonstrated substantial improvement in pain and symptoms. Bilateral knee pain has emerged as a confounding factor in clinical trials when evaluating the effect of a single intra-articular injection. Furthermore, unilateral disease is frequently first to emerge in active military personnel secondary to prior traumatic joint injury. In this post hoc analysis, we assessed efficacy and safety of TA-ER in a subgroup of participants with unilateral knee OA.
Participants ≥ 40 years of age with symptomatic knee OA were randomized to a single intra-articular injection of TA-ER 32 mg, TA crystalline suspension (TAcs) 40 mg, or saline-placebo. Average daily pain (ADP)-intensity and rescue medication use were collected at each of weeks 1-24 postinjection; Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC)-A (pain), WOMAC-B (stiffness), WOMAC-C (function), and Knee Injury and Osteoarthritis Outcome Score Quality of Life (KOOS-QoL) were collected at weeks 4, 8, 12, 16, 20, and 24 postinjection. Adverse events (AEs) were assessed throughout the study. Participants with unilateral knee OA were selected for this analysis.
Of 170 participants with unilateral OA (TA-ER, N = 51; saline-placebo, N = 60; TAcs, N = 59), 42% were male and 89% were white. TA-ER significantly (p < 0.05) improved ADP-intensity vs. saline-placebo (weeks 1-24) and TAcs (weeks 4-21). TA-ER significantly (p < 0.05) improved WOMAC-A vs. saline-placebo (all time points) and TAcs (weeks 4, 8, 12, 24). Consistent outcomes were observed for rescue medication, WOMAC-B, WOMAC-C, and KOOS-QoL. AEs were similar in frequency/type across treatments.
TA-ER provided 5-6 months' pain relief that consistently exceeded saline-placebo and TAcs, suggesting that TA-ER injected intra-articularly into the affected knee may be an effective non-opioid treatment option. Although the participants included in this analysis did not fully represent the diverse demographics of active service members, the substantial unmet medical need in the military population suggests that TA-ER may be an important treatment option; additional studies of TA-ER in active military patients are needed.
ClinicalTrials.gov NCT02357459.
Flexion Therapeutics, Inc. Plain language summary available for this article.
骨关节炎（OA）较为常见，其在军人中的发病率更高。在一项 3 期随机对照试验（NCT02357459）中，在患有单侧或双侧膝骨关节炎的参与者中，单次关节内注射曲安奈德延释制剂（TA-ER）可显著改善疼痛和症状。当评估单次关节内注射的效果时，双侧膝关节疼痛已成为临床试验中的一个混杂因素。此外，由于先前的关节创伤性损伤，现役军人中经常首先出现单侧疾病。在这项事后分析中，我们评估了 TA-ER 在单侧膝骨关节炎亚组参与者中的疗效和安全性。
≥40 岁、有症状的膝骨关节炎参与者被随机分配至单次关节内注射 TA-ER 32mg、TA 晶体混悬剂（TAcs）40mg 或生理盐水安慰剂。在注射后第 1-24 周的每周收集平均每日疼痛（ADP）强度和急救药物使用情况；在注射后第 4、8、12、16、20 和 24 周收集 Western Ontario 和 McMaster 大学骨关节炎指数（WOMAC）-A（疼痛）、WOMAC-B（僵硬）、WOMAC-C（功能）和膝关节损伤和骨关节炎结果评分生活质量（KOOS-QoL）。整个研究过程中评估不良事件（AE）。选择单侧膝骨关节炎患者进行这项分析。
在 170 名单侧 OA 患者（TA-ER，N=51；生理盐水安慰剂，N=60；TAcs，N=59）中，42%为男性，89%为白人。与生理盐水安慰剂（第 1-24 周）和 TAcs（第 4-21 周）相比，TA-ER 显著（p<0.05）改善 ADP 强度。与生理盐水安慰剂（所有时间点）和 TAcs（第 4、8、12、24 周）相比，TA-ER 显著（p<0.05）改善 WOMAC-A。在急救药物、WOMAC-B、WOMAC-C 和 KOOS-QoL 方面也观察到了一致的结果。治疗组之间的 AE 发生频率/类型相似。
TA-ER 提供了 5-6 个月的疼痛缓解，持续优于生理盐水安慰剂和 TAcs，这表明 TA-ER 关节内注射到受累膝关节可能是一种有效的非阿片类治疗选择。尽管本分析中纳入的参与者不能完全代表现役军人的多样化人口统计学特征，但军队人群中存在大量未满足的医疗需求，这表明 TA-ER 可能是一个重要的治疗选择；需要对现役军人患者中的 TA-ER 进行更多研究。
ClinicalTrials.gov NCT02357459。
Flexion Therapeutics，Inc. 本文提供通俗易懂的摘要。
