Topical maxacalcitol for the treatment of psoriasis vulgaris: a placebo‐controlled, double‐blind, dose‐finding study with active comparator
Topical maxacalcitol for the treatment of psoriasis vulgaris: a placebo‐controlled, double‐blind, dose‐finding study with active comparator
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外用马沙骨化醇治疗寻常型银屑病：一项安慰剂对照、双盲、活性对照剂量探索研究
DOI：
10.1046/j.1365-2133.1999.02975.x
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发表时间：
1999
影响因子：
10.3
通讯作者：
J. Berth‐Jones
中科院分区：
文献类型：
--
作者：
J. Barker;R. Ashton;R. Marks;R. I. Harris;J. Berth‐Jones
1α，25-二羟基-22-氧代骨化三醇（maxacalcitol）是一种维生素D3类似物，在体外抑制角质形成细胞增殖方面的功效比卡泊三醇和他卡西醇高约10倍。为了确定临床疗效，在轻度至中度慢性斑块状银屑病患者中进行了一项II期、双盲、随机、左vs.右、浓度-效应研究，每日一次外用马沙骨化醇。主要疗效参数为银屑病严重程度指数（PSI），基于红斑、鳞屑和硬结的评分总和以及研究者对治疗8周时患者对治疗反应的总体评估。144名患者参与了研究。所有浓度的马沙骨化醇软膏（6、12.5、25和50 μg/g）在降低PSI方面均比安慰剂显著更有效（P <0.01），其中马沙骨化醇25 μg/g的效果最大。 钙泊三醇软膏50 μg/g每日一次作为活性对照药物具有相似的效果。 马沙骨化醇25 μg/g（55%的受试者）对银屑病的显著改善或清除效果最好，优于卡泊三醇（46%）。 在整个研究期间持续改善，在第8周没有达到平台期。研究者和患者的副作用偏好（次要疗效参数）评定马沙骨化醇比安慰剂更有效，25 μg/g马沙骨化醇优于卡泊三醇（研究者评估P<0.05）。 12例患者因不良事件退出研究，其中4例被判定为与研究药物有关。这项研究表明，每天一次的maxacalcitol软膏可有效治疗斑块状银屑病，在25 μg/g时观察到最大效果。 由于在8周时没有观察到反应平台，这些数据表明，如果使用maxacalcitol软膏更长时间，可能会获得进一步的益处。最后，研究者的总体评估和副作用偏好表明，maxacalcitol 25 μg/g可能比每日一次的钙泊三醇更有效。
1α, 25‐Dihydroxy‐22‐oxacalcitriol (maxacalcitol) is a vitamin D3 analogue which displays approximately 10 times greater efficacy at suppressing keratinocyte proliferation in vitro than calcipotriol and tacalcitol. To determine clinical efficacy, a phase II double‐blind, randomized, left vs. right, concentration–response study was performed with once‐daily topical maxacalcitol in patients with mild to moderate chronic plaque psoriasis. Primary efficacy parameters were psoriasis severity index (PSI) based on sum of scores for erythema, scaling and induration and investigators' overall assessment of patients' response to therapy at 8 weeks of treatment. One hundred and forty‐four patients participated. All concentrations of maxacalcitol ointment (6, 12.5, 25 and 50 μg/g) were significantly more effective at reducing PSI than placebo (P < 0.01), with greatest effect noted for maxacalcitol 25 μg/g. Calcipotriol ointment 50 μg/g once daily as active comparator had a similar effect. Marked improvement or clearance of psoriasis was greatest for maxacalcitol 25 μg/g (55% of subjects) which compared favourably with calcipotriol (46%). Improvement continued throughout the study period, with no plateau at week 8. Investigators' and patients' side preference (secondary efficacy parameters) rated maxacalcitol more effective than placebo and 25 μg/g maxacalcitol better than calcipotriol (P < 0.05 for investigators' assessment). Twelve patients withdrew from the study due to adverse events, of which four were judged to be due to study medication. This study indicates that once‐daily maxacalcitol ointment is effective in the management of plaque psoriasis, with greatest effect noted at 25 μg/g. As no response plateau was noted at 8 weeks, these data suggest that further benefit might be obtained if maxacalcitol ointment were applied for longer. Finally, investigators' overall assessment and side preference suggest that maxacalcitol 25 μg/g may be more effective than once‐daily calcipotriol.