Department of Rheumatology & Immunology, Singapore General Hospital, Singapore; Office of Clinical, Academic & Faculty Affairs, Duke-NUS Medical School, Singapore.
Population Health Sciences, University of Utah, USA.
Osteoarthritis Cartilage. 2018 May;26(5):631-640. doi: 10.1016/j.joca.2018.01.026. Epub 2018 Feb 7.
Uric acid may activate an innate immune response in osteoarthritis (OA), contributing to disease pathology and progression. We evaluated the effectiveness of colchicine on pain and function in symptomatic knee OA (KOA) and the underlying mechanism of action.
Colchicine effectiveness in symptoms and inflammation modification in knee osteoarthritis (COLKOA) was a double-blind, placebo-controlled, randomized trial comparing 16 weeks of treatment with 0.5 mg twice-daily oral colchicine to placebo for knee osteoarthritis (KOA). The primary endpoint was ≥30% improvement in total Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score at week 16. Secondary endpoints included improvement in pain (0-10 Likert scales); WOMAC pain; patient global assessment (0-100); physical function; the OARSI-OMERACT response; quality of life; and change in serum, urine, synovial fluid (SF) biomarkers of cartilage metabolism and inflammation, and plasma/SF colchicine concentrations.
Of 109 randomly assigned participants, 39% (95% confidence interval (CI) 27-52%) and 49% (95% CI 36-62%) in the colchicine and placebo arms respectively met the primary endpoint at study end (P = 0.284, odds ratio 0.66, 95% CI 0.31-1.41). No strong evidence of treatment differences was identified on clinical secondary endpoints. Treatment significantly reduced mean serum hs-CRP (P = 0.008) and SF CTXI (P = 0.002); treatment tended to reduce inflammatory markers (SF IL-6, IL8, TNFα, CD14 and IL-18), but these differences were not statistically significant.
Colchicine (0.5 mg twice-daily orally) reduced inflammation and high bone turnover biomarkers known to be associated with OA severity and progression risk, but did not reduce KOA symptoms over a 16-week study period. A longer-term study to evaluate for slow-acting disease modifying effects is warranted.
The trial has been registered at clinicaltrials.gov as NCT02176460. Date of registration: June 26, 2014.
尿酸可能会在骨关节炎（OA）中激活先天免疫反应，从而导致疾病的病理和进展。我们评估了秋水仙碱对有症状的膝关节骨关节炎（KOA）的疼痛和功能的疗效，以及其作用机制。
秋水仙碱对膝骨关节炎（KOA）症状和炎症的疗效（COLKOA）是一项双盲、安慰剂对照、随机试验，比较了 16 周 0.5mg 每日两次口服秋水仙碱与安慰剂治疗膝骨关节炎（KOA）的疗效。主要终点是在第 16 周时总西部安大略省和麦克马斯特大学骨关节炎指数（WOMAC）评分改善≥30%。次要终点包括疼痛改善（0-10 级 Likert 量表）；WOMAC 疼痛；患者总体评估（0-100）；身体功能；OARSI-OMERACT 反应；生活质量；以及血清、尿液、滑液（SF）软骨代谢和炎症生物标志物以及血浆/SF 秋水仙碱浓度的变化。
在 109 名随机分配的参与者中，秋水仙碱组和安慰剂组分别有 39%（95%置信区间[CI] 27-52%）和 49%（95% CI 36-62%）在研究结束时达到主要终点（P=0.284，优势比 0.66，95% CI 0.31-1.41）。在临床次要终点上，没有发现治疗差异的有力证据。治疗显著降低了平均血清 hs-CRP（P=0.008）和 SF CTXI（P=0.002）；治疗倾向于降低炎症标志物（SF IL-6、IL8、TNFα、CD14 和 IL-18），但这些差异没有统计学意义。
秋水仙碱（0.5mg 每日两次口服）降低了与 OA 严重程度和进展风险相关的炎症和高骨转换生物标志物，但在 16 周的研究期间并未减轻 KOA 症状。需要进行更长时间的研究来评估其是否具有缓慢作用的疾病修饰作用。
该试验已在 clinicaltrials.gov 上注册，编号为 NCT02176460。注册日期：2014 年 6 月 26 日。
