Supplementary Material for: Clinical effects of oral supplementation of gamma-ciclodextrin curcumin complex in male patients with moderate-to-severe BPH-related Lower Urinary Tract Symptoms

Introduction: Benign prostatic hyperplasia (BPH) is the most common cause of lower urinary tract symptoms (LUTS) in males. Curcumin exhibits anti-inflammatory and anti-tumor properties which may be effective for BPH. This multi-arm observational study evaluated the real-world efficacy of QURMIN® (Gamma-cyclodextrin-curcumin Complex-CAVACURMIN®) as single or combination therapy for BPH. Methods: Men with moderate-severe LUTS/BPH receiving a 6-month supplementation with QURMIN® alone or in combination with BPH-specific medication were propensity score matched with patients not taking curcumin and then divided into subgroups based on concomitant baseline treatment. Cohorts were compared in the 6-month variation of IPSS, quality of life (IPSS-QoL), Benign prostatic Hyperplasia Impact Index (BII) and uroflowmetry parameters. Curcumin tolerability was evaluated in terms of discontinuations and adverse effects. Results: The 1:1 propensity score matching resulted in a treatment-naïve (n=152), an alpha-blocker only(AB)(n=138) and a AB+5-alpha reductase inhibitors (5-ARI) (n=78) subgroup. After 6 months, drug-naïve patients taking curcumin reported significant improvement in IPSS-storage (-3.9,p<0.001), IPSS-voiding(-2.0,p=0.011), IPSS-total(-5.9,p<0.001), IPSS-QoL(-3.9,p<0.001), BII(-2.0,p<0.001), Qmax(+3.1 ml/s,p<0.001), Qmean(+1.9 ml/s,p=0.005), PVR(-7.7 ml,p<0.001), and PSA(-0.3 ng/ml,p=0.003), compared to controls. Patients taking ABs and curcumin showed improvement in IPSS-storage(-2.7,p<0.001), IPSS-voiding(-1.3,p=0.033), IPSS-total(-3.5,p<0.001), IPSS-QoL(-1.1,p=0.004), BII(-1.7,p=0.006), Qmax(+1.0 ml/s,p=0.006) and PSA(-0.2 ng/ml,p=0.01). Patients taking curcumin and AB+5-ARI showed improvement in IPSS-storage(-1.3,p=0.007), IPSS-total(-1.6,p=0.034), IPSS-QoL(-1.1,p<0.001) and BII(-2.0,p<0.001). No adverse reactions were reported for curcumin supplementation. Conclusion: QURMIN® (CAVACURMIN®) led to significant improvements in symptom burden, uroflow parameters and QoL, without significant additional side effects, thus proving to be a potential new treatment for BPH, either as a single therapy or in addition to standard treatment.

引言：良性前列腺增生（Benign prostatic hyperplasia, BPH）是男性下尿路症状（lower urinary tract symptoms, LUTS）最常见的致病原因。姜黄素（curcumin）具备抗炎与抗肿瘤特性，或可用于良性前列腺增生的治疗。本多臂观察性研究评估了QURMIN®（γ-环糊精-姜黄素复合物-CAVACURMIN®）单药或联合疗法用于良性前列腺增生的真实世界疗效。方法：纳入存在中重度下尿路症状/良性前列腺增生的男性患者，予其QURMIN®单药或联合前列腺增生特异性药物治疗，疗程为6个月；通过倾向得分匹配（propensity score matching）将受试者与未服用姜黄素的患者配对，并根据基线伴随治疗情况划分亚组。对比各组患者6个月后国际前列腺症状评分（IPSS）、IPSS生活质量评分（IPSS-QoL）、良性前列腺增生影响指数（BII）以及尿流参数的变化情况；同时从停药率与不良反应两方面评估姜黄素的耐受性。结果：经1:1倾向得分匹配后，共得到3个亚组：初治组（treatment-naïve, n=152）、仅α受体阻滞剂（alpha-blocker, AB）组（n=138）以及α受体阻滞剂+5-α还原酶抑制剂（5-alpha reductase inhibitor, 5-ARI）组（n=78）。治疗6个月后，与对照组相比，初治且服用姜黄素的患者在多项指标上出现显著改善：IPSS储尿分项(-3.9, p<0.001)、IPSS排尿分项(-2.0, p=0.011)、IPSS总分(-5.9, p<0.001)、IPSS-QoL(-3.9, p<0.001)、BII(-2.0, p<0.001)、最大尿流率(Qmax)(+3.1 ml/s, p<0.001)、平均尿流率(Qmean)(+1.9 ml/s, p=0.005)、残余尿量(PVR)(-7.7 ml, p<0.001)以及前列腺特异性抗原(PSA)(-0.3 ng/ml, p=0.003)。服用α受体阻滞剂联合姜黄素的患者则出现如下改善：IPSS储尿分项(-2.7, p<0.001)、IPSS排尿分项(-1.3, p=0.033)、IPSS总分(-3.5, p<0.001)、IPSS-QoL(-1.1, p=0.004)、BII(-1.7, p=0.006)、Qmax(+1.0 ml/s, p=0.006)以及PSA(-0.2 ng/ml, p=0.01)。服用姜黄素联合AB+5-ARI的患者仅在IPSS储尿分项(-1.3, p=0.007)、IPSS总分(-1.6, p=0.034)、IPSS-QoL(-1.1, p<0.001)以及BII(-2.0, p<0.001)上出现显著改善。本研究未报告姜黄素补充治疗相关的不良反应。结论：QURMIN®（CAVACURMIN®）可显著改善良性前列腺增生患者的症状负荷、尿流参数与生活质量，且未出现显著额外不良反应，证明其无论是作为单药疗法还是标准治疗的联合用药，均为良性前列腺增生潜在的新型治疗方案。