Apocynin (AP) and paeonol (PA) are low molecular weight phenolic compounds with a broad array of anti-inflammatory and immunoregulatory effects. This study assessed of a fixed-dose combination of APPA in people with symptomatic knee osteoarthritis (OA). A multi-center, randomized, placebo-controlled, double-blind phase 2a trial enrolled participants with radiographic knee OA (Kellgren-Lawrence, KL, grades 2–3) and pain ≥40/100 on WOMAC pain subscale, and evaluated the efficacy and safety of oral APPA over a 28-day period. APPA 800 mg or matching placebo was administered twice daily in a 1:1 ratio. Post-hoc analyses explored the response to APPA in sub-groups with more severe pain and structural severity. The two groups were comparable at baseline; 152 subjects were enrolled and 148 completed the trial. There was no statistically significant difference between groups with respect to the primary outcome, WOMAC pain (mean difference between groups was −0.89, 95% CI: −5.62, 3.84, p = 0.71), nor WOMAC function or WOMAC total. However, predefined subgroup analyses of subjects with symptoms compatible with nociplastic/neuropathic pain features showed a statistically significant effect of APPA compared to placebo. Adverse events (mainly gastrointestinal) were mild to moderate. Treatment with APPA 800 mg twice daily for 28 days in subjects with symptomatic knee OA was not associated with significant symptom improvement compared to placebo. The treatment was well-tolerated and safe. While the study was not powered for such analysis, pre-planned subgroup analyses showed a significant effect of APPA in subjects with nociplastic pain/severe OA, indicating that further research in the effects of APPA in appropriate patients is warranted.

中文翻译：

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夹竹桃麻素和丹皮酚固定剂量组合 (APPA) 在症状性膝关节 OA 中的功效和安全性：一项双盲、随机、安慰剂对照临床试验


罗布麻宁 (AP) 和丹皮酚 (PA) 是低分子量酚类化合物，具有广泛的抗炎和免疫调节作用。本研究评估了固定剂量的 APPA 组合对有症状的膝骨关节炎 (OA) 患者的治疗效果。一项多中心、随机、安慰剂对照、双盲 2a 期试验招募了患有放射学膝关节 OA（Kellgren-Lawrence，KL，2-3 级）且 WOMAC 疼痛量表疼痛≥40/100 的参与者，并评估了疗效28 天内口服 APPA 的安全性。 APPA 800 mg 或匹配的安慰剂以 1:1 的比例每天给药两次。事后分析探讨了疼痛和结构严重程度更严重的亚组对 APPA 的反应。两组在基线时具有可比性；共有 152 名受试者入组，其中 148 名受试者完成了试验。在主要结局、WOMAC 疼痛（组间平均差异为 -0.89，95% CI：-5.62、3.84，p = 0.71）、WOMAC 功能或 WOMAC 总计方面，组间没有统计学显着差异。然而，对症状符合伤害性/神经性疼痛特征的受试者的预定义亚组分析显示，与安慰剂相比，APPA 具有统计学上显着的效果。不良事件（主要是胃肠道）为轻度至中度。与安慰剂相比，有症状的膝关节 OA 受试者接受 APPA 800 mg 每天两次、持续 28 天的治疗与明显的症状改善无关。该治疗耐受性良好且安全。虽然该研究没有为此类分析提供动力，但预先计划的亚组分析显示 APPA 对伤害性疼痛/严重 OA 受试者有显着影响，表明有必要进一步研究 APPA 对适当患者的影响。