1Hillcrest Clinical Research, Oklahoma City, OK.
2Axis Clinical Trials, Los Angeles, CA.
J Altern Complement Med. 2019 Aug;25(8):845-855. doi: 10.1089/acm.2019.0121. Epub 2019 Jul 8.
To evaluate purified honey bee () venom (HBV) biotherapy for the treatment of osteoarthritis (OA) knee pain and physical function. Five hundred and thirty-eight patients with Kellgren/Lawrence grade 1-3 radiographic knee OA and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score ≥2 were randomized 1:2 to either control ("histamine") or HBV in this double-blind study. After a dose escalation period, patients received 12 weekly dermal injections of control ("histamine") or HBV. At each of the 12 weekly visits, a set of 15 dermal injections (each containing 2.75 μg histamine or 100 μg HBV) were administered at prespecified acupuncture points (5 on each knee: knee top, eye-1 medial, eye-2 lateral, ST 34, BL 40 and 5 near the spinous processes: BL 19, 21, 23, 25, and 27). Assessments included WOMAC pain and physical function subscales, visual analog scale (VAS), patient global assessment (PGA), and physician global assessment (PhGA). Rescue medication use (acetaminophen) and routine safety parameters were monitored. HBV biotherapy demonstrated a highly significant improvement over control in WOMAC pain score after 12 weeks (1.1 U mean difference; confidence interval [95% CI]: 0.3-2.0; analysis of covariance [ANCOVA] = 0.0010 with baseline as covariate) that was also sustained 4 weeks post-treatment. Furthermore, WOMAC physical function was significantly improved over control with HBV (3.1 U mean difference; 95% CI: 0.3-5.9; ANCOVA = 0.0046), and sustained 4 weeks post-treatment. VAS scores were significantly improved with HBV versus control, as well as PGA and PhGA evaluations, which showed that patients responded more favorably ("very good/good") to their overall OA condition (82.0% vs. 62.4% [ = 0.0001] and 82.1% vs. 54.9% [ = 0.0015], respectively). Use of rescue acetaminophen was similar between the groups (77%-78% of patients). HBV was associated with higher incidence of injection site reactions (<5%); however, the overall safety profiles were comparable between the treatment groups. This phase 3 trial demonstrated that HBV biotherapy resulted in significant improvements in knee OA pain and physical function.
评估纯化的蜜蜂（）毒液（HBV）生物疗法治疗骨关节炎（OA）膝关节疼痛和身体功能。 这项双盲研究纳入了 538 名 Kellgren/Lawrence 分级 1-3 级放射学膝关节 OA 和 Western Ontario 和 McMaster 大学骨关节炎指数（WOMAC）疼痛评分≥2 的患者，随机分为对照组（“组胺”）或 HBV 组，比例为 1:2。 在剂量递增期后，患者接受 12 周每周一次的真皮注射，分别接受对照组（“组胺”）或 HBV 治疗。在每 12 周的就诊中，在预先指定的穴位（每只膝关节 5 个穴位：膝关节顶部、眼 1 内侧、眼 2 外侧、ST 34、BL 40 和靠近棘突的 5 个穴位：BL 19、21、23、25 和 27）注射一组 15 个真皮注射（每个注射部位含有 2.75μg 组胺或 100μg HBV）。 评估包括 WOMAC 疼痛和身体功能子量表、视觉模拟量表（VAS）、患者总体评估（PGA）和医生总体评估（PhGA）。 监测了救急药物（对乙酰氨基酚）的使用情况和常规安全性参数。 HBV 生物疗法在 12 周后在 WOMAC 疼痛评分方面显示出与对照组相比的显著改善（平均差异 1.1U；置信区间[95%CI]：0.3-2.0；协方差分析[ANCOVA] = 0.0010，以基线为协变量），并且在治疗后 4 周仍持续。 此外，与对照组相比，HBV 也显著改善了 WOMAC 身体功能（平均差异 3.1U；95%CI：0.3-5.9；ANCOVA = 0.0046），并且在治疗后 4 周仍持续。 VAS 评分也显著优于对照组，PGA 和 PhGA 评估也显示患者对整体 OA 状况的反应更为良好（82.0% vs. 62.4%[ = 0.0001]和 82.1% vs. 54.9%[ = 0.0015]）。 两组患者的救急乙酰氨基酚使用率相似（77%-78%的患者）。 HBV 与注射部位反应的发生率较高（<5%）相关；然而，治疗组之间的总体安全性特征相当。 这项 3 期试验表明，HBV 生物疗法可显著改善膝关节 OA 疼痛和身体功能。
