重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白治疗寻常性银屑病多中心、随机、双盲试验

目的 评价注射用重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白(rhTNFR:Fc,商品名益赛普)治疗中、重度寻常性银屑病的临床疗效和安全性.方法 采用多中心、随机、双盲双模拟、阳性药物平行对照的临床试验.4个研究中心共144例中、重度寻常性银屑病患者,随机分为试验组和对照组,试验组皮下注射rhTNFR:Fc 50 mg/周,同时口服空白模拟甲氨蝶呤7.5 mg/周;对照组口服甲氨蝶呤7.5 mg/周,同时皮下注射空白模拟rhTNFR:Fc 50 mg/周,疗程12周.结果 124例患者完成了试验,治疗12周后,试验组PAS150、PASI75、PASI90的比例分别为86.11%,76.39%,52.78%,对照组分别为63.89%,44.44%,22.22%,两组间差异有统计学意义(P<0.01).医生对病情的整体评分、皮肤病生活质量指数和患者10 cm视觉模拟评分试验组改善优于对照组(P<0.05);试验组达到痊愈和几乎达到痊愈的比例显著高于对照组(P<0.05).不良反应主要有白细胞或中性粒细胞下降、感染、肝功能异常、注射局部水肿、瘙痒等,发生率试验组为26.39%,对照组为29.17%,两组差异无统计学意义(P>0.05),未见严重不良反应.结论 rhTNFR:Fc比甲氨蝶呤起效快,治愈率高,且毒性反应小.     

曲尼司特胶囊治疗瘢痕疙瘩的多中心随机双盲平行对照研究

目的 评价曲尼司特胶囊治疗瘢痕疙瘩的临床疗效和安全性。方法 采用多中心、随机、安慰剂平行对照的临床研究方法，将入选患者随机分为治疗组和对照组，分别接受口服曲尼司特和安慰剂治疗，两组均同时外用多磺酸黏多糖（商品名喜辽妥），于治疗后第4、8、12周随访。主要疗效指标为皮损的B超厚度，次要指标为皮损硬度、瘙痒及疼痛的评分。结果 共有143例瘢痕疙瘩患者参加本次研究，符合研究方案完成试验者124例，其中治疗组60例，对照组64例。研究结束时，主要疗效指标皮损厚度的下降率，治疗组和对照组间的差异有统计学意义（P=0．001）；综合评分的下降率，治疗组和对照组的有效率分别为15．00％、4．69％（P=0．046），差异有统计学意义。两组不良事件的发生率分别为5．88％和2．86％，差异无统计学意义（P=0．438）。结论 曲尼司特胶囊治疗瘢痕疙瘩安全并有一定作用。     

Treatment of psoriasis with topical sirolimus: preclinical development and a randomized, double-blind trial

BACKGROUND: Systemically administered sirolimus has demonstrated efficacy in psoriasis in a multicentre European study. OBJECTIVES: To determine the efficacy and safety of topically applied sirolimus in treating psoriasis. METHODS: In vitro studies were followed by a pilot study designed to determine if sirolimus penetrates human skin, and by a randomized, double-blind, left-right comparative, dose-ranging study consisting of treatment with 2.2% sirolimus for 6 weeks and 8% sirolimus for an additional 6 weeks in 24 patients with stable, chronic plaque psoriasis. The primary outcome measure was clinical score. Secondary measures were ultrasound plaque thickness, plaque erythema, and computerized image analysis of immunohistochemical stains for immunocytes and proliferating cells. Pharmacokinetics and blood chemistry monitoring for safety were also performed. RESULTS: A significant reduction in the clinical score (P = 0.03) (mean score 9.1 following sirolimus vs. 11.2 in control) was achieved with topical sirolimus. Measurements of plaque thickness and erythema did not show significant improvement with treatment. Computerized image analysis of biopsies showed a significant reduction in CD4+ cells (P = 0.0054) and proliferating cells (stained by Ki-67) in the epidermis (P = 0.0153) with sirolimus treatment compared with control. CONCLUSIONS: Topically applied sirolimus penetrates normal skin and may have some antipsoriatic and immunosuppressive activity.     

Clinical and immunologic assessment of patients with psoriasis in a randomized,double-blind,placebo-controlled trial using recombinant human interleukin 10

BACKGROUND: In several open-label studies, recombinant human interleukin 10 (rhIL-10), a type 2 anti-inflammatory cytokine, has been reported to improve psoriasis, a disease characterized by type 1 cytokine inflammation. OBJECTIVE: To evaluate the safety, efficacy, and immunologic parameters in individuals with psoriasis treated with rhIL-10. DESIGN AND INTERVENTION: Patients received rhIL-10 (20 micro g/kg) or placebo subcutaneously 3 times weekly for 12 weeks in a randomized, double-blind manner. SETTING AND PATIENTS: National Institutes of Health Clinical Center in Bethesda. Twenty-eight patients with moderate-to-severe psoriasis as defined by a Psoriasis Area Severity Index (PASI) score of 10 or higher. MAIN OUTCOME MEASURE: The primary clinical end point was the mean percentage change in the PASI score comparing baseline and week 12 scores. Intracellular cytokine production by peripheral blood mononuclear cells (PBMCs) was measured by flow cytometry. RESULTS: There was no significant difference in the mean percentage change in the PASI score from baseline to week 12 between the rhIL-10-treated group and control patients (17% vs 13% improvement, respectively; P =.69), although a modest trend toward improvement in patients receiving rhIL-10 was documented at both the 6- and 8-week points. Interestingly, proinflammatory and type 1 cytokine production by PBMCs progressively declined in the rhIL-10-treated patients during the entire 12-week study period. CONCLUSIONS: Treatment with rhIL-10 resulted in only temporary clinical improvement in psoriasis, despite sustained systemic decreases in proinflammatory and type 1 cytokine production. These data suggest that immunotherapy that decreases the ratio of systemic type 1 and type 2 cytokine production does not necessarily lead to improvement of type 1 cytokine-mediated disease.     

Pharmacology and Treatment Maintenance treatment of psoriasis by Tigason: a double-blind randomized clinical trial

Extensive lesions on 36 patients with psoriasis were treated by Tigason, I mg/kg/day plus PUVA until skin clearance. A clinical score was calculated for each body area, and erythema, scaling, thickness and pruritus of the lesions were scored from 0 to 3. Skin clearing was defined as a clinical score less than 10% of the initial score. Double-blind maintenance treatment was then started. This was Tigason at half of the maximal dose tolerated during the clearing phase of the treatment v. placebo. Relapse of the disease was defined as the occurrence of a clinical score greater than 50% of the initial score. Among the 36 patients randomized, 20 received placebo and 16 received Tigason. Relapses increased quickly in the patients on placebo, but occurred in few patients treated by Tigason with 60% remaining clear after 1 year (P less than 0.05). Surprisingly, the kinetics of disappearance of the most frequent side effect, cheilitis, was the same in the Tigason group and in the placebo group. This double-blind randomized clinical trial shows that Tigason at low doses is an efficient and well-tolerated maintenance treatment of psoriasis.     

Folic acid supplementation during treatment of psoriasis with methotrexate: a randomized, double-blind, placebo-controlled trial

BACKGROUND: The value of folate supplementation in methotrexate (MTX)-treated patients remains controversial. OBJECTIVES: To determine the effect of folic acid (FA) on the efficacy of MTX and the frequency of side-effects associated with MTX therapy. METHODS: A 12-week double-blind clinical trial was conducted in patients with psoriasis stable on their long-term MTX doses but not receiving FA. They were randomized into two arms of either FA 5 mg or placebo daily. MTX doses were not changed throughout the study. Patients were monitored every 3 weeks by the same observer. Assessments included Psoriasis Area and Severity Index (PASI), a visual analogue scale (VAS) of patients' perception of their psoriasis severity and the Dermatology Life Quality Index (DLQI). Adverse events were systematically recorded. Haematological and biochemical monitoring was performed. RESULTS: Twenty-two patients with psoriasis were recruited. Age, sex and weekly MTX doses were similar in both groups. All 22 patients completed the study. The mean PASI in the FA group increased from 6.4 at baseline to 10.8 at 12 weeks. In the placebo group the mean PASI fell from 9.8 at baseline to 9.2 at 12 weeks. The mean change from baseline in the FA group was 4.4 vs. -0.6 in the placebo group (P < 0.05). Similar trends were observed in the changes in VAS and in the DLQI and differences between the groups were significant for both these parameters (P < 0.05). Few adverse effects were reported. CONCLUSIONS: This study suggests that supplementation with FA during long-term MTX treatment reduces the efficacy of MTX in the control of psoriasis. Due to the relatively small sample size and short duration of this study, no conclusions can be drawn regarding the possibility that FA may reduce the side-effects of MTX.     

An international,randomized, double-blind,placebo-controlled phase 3 trial of intramuscular alefacept in patients with chronic plaque psoriasis

BACKGROUND: Alefacept, human lymphocyte function-associated antigen 3/immunoglobulin 1 fusion protein, binds to CD2 molecules on the surface of activated T cells, selectively targeting memory-effector (CD45RO+) T cells, which comprise more than 75% of T cells in psoriatic plaques. OBJECTIVE: To examine the efficacy and tolerability of intramuscular alefacept. DESIGN: International, randomized, double-blind, placebo-controlled, parallel-group trial. PATIENTS: A total of 507 patients with chronic plaque psoriasis. INTERVENTION: Placebo, 10 mg of alefacept, or 15 mg of alefacept administered once weekly for 12 weeks followed by 12 weeks of observation. MAIN OUTCOME MEASURE: Psoriasis Area Severity Index (PASI). RESULTS: Alefacept treatment was associated with dose-related significant improvements in PASI from baseline. Throughout the study, a greater percentage of patients in the 15-mg group than in the placebo group achieved a significant reduction in PASI. Of patients in the 15-mg group who achieved at least 75% PASI reduction 2 weeks after the last dose, 71% maintained at least 50% improvement in PASI throughout the 12-week follow-up. There were no opportunistic infections and no cases of disease rebound. CONCLUSION: Intramuscular administration of alefacept was a well-tolerated and effective therapy for chronic plaque psoriasis and thus represents a convenient alternative to intravenous dosing.     

Ketoconazole compared with griseofulvin in dermatophytoses: a randomized, double-blind trial

50 patients with drug-resistant and/or extensive superficial mycoses and positive cultures for dermatophytes, were randomly assigned to treatment either with 200 mg ketoconazole (26 patients, mean age 31 years) or 500 mg griseofulvin (24 patients, mean age 32.5 years) daily, administered in identical capsules. Patients were evaluated before and during treatment, clinically, by direct microscopy and cultures in double-blind conditions. The maximum duration of treatment was 6 weeks. 26/26 patients in the ketoconazole group and 22/24 patients in the griseofulvin group had negative cultures after 2.5 and 3 weeks (median values) respectively. Clinical symptoms responded rapidly and completely to both treatments. Therapeutic results were statistically significant in both groups. 1 patient in each group relapsed during the next 3 months after the end of the treatment. No unwanted effects were reported. Although both treatments were effective, therapeutic results were slightly better and appeared earlier with ketoconazole.     

曲尼司特胶囊治疗特应性皮炎的多中心随机双盲对照研究

目的评价曲尼司特胶囊治疗特应性皮炎的安全性和有效性。方法采用多中心、随机双盲、安慰剂平行对照的研究方法，将入选患者随机分为治疗组和对照组，分别接受曲尼司特和安慰剂治疗，于治疗前（基线）及治疗后第1～3周访视1次，连续4周。主要疗效指标为SCORAD，次要疗效指标包括炎症性皮损范围指数、瘙痒的视觉模拟评分及影响睡眠评分等。结果共144例特应性皮炎患者（曲尼司特治疗组和安慰剂对照组各72例）参加本研究，其中139例（曲尼司特治疗组70例，安慰剂对照组69例）纳入疗效可评估分析集（FAS）。研究结束根据SCORAD下降进行评价时，治疗组和对照组的有效率分别为61．43％和24．64％，两组间差异有统计学意义（P=0．0001）。用药2、3、4周后，SCORAD评分、瘙痒的视觉模拟评分及影响睡眠评分等指标均显著下降，两组比较差异有统计学意义（P〈0．05）。治疗组少数患者出现胸闷、嗜睡等现象。两组不良事件的发生率为8．45％和11．43％，两组差异无统计学意义。结论曲尼司特胶囊治疗特应性皮炎安全有效。     

Oral pimecrolimus in the treatment of moderate to severe chronic plaque-type psoriasis: a double-blind, multicentre, randomized, dose-finding trial

BACKGROUND: There is a need for safe and effective alternative treatments for patients with moderate to severe psoriasis. OBJECTIVES: Pimecrolimus is a calcineurin inhibitor that is being investigated in oral form for the treatment of psoriasis. PATIENTS AND METHODS: A double-blind, randomized, parallel-group, dose-finding study was performed. Healthy adult outpatients with moderate to severe chronic plaque-type psoriasis (n = 143) were randomized to receive oral placebo or pimecrolimus 10 mg, 20 mg or 30 mg twice daily (b.d.) for 12 weeks. Main outcome measures: The Psoriasis Area and Severity Index (PASI) was used to assess clinical severity of psoriasis. Results were analysed at weeks 7 (primary endpoint) and 13. Safety was assessed by monitoring all adverse events, laboratory investigations (blood chemistry, urinalysis, haematology) and physical examinations. RESULTS: The change from baseline in PASI at week 7 showed a dose-dependent effect. The differences between each of the two higher doses of pimecrolimus and placebo were statistically significant (P < 0.001; ANOVA). The mean percentage decreases from baseline in PASI in the placebo group and pimecrolimus 10 mg, 20 mg and 30 mg b.d. groups at week 7 were 3.1%, 22.2%, 51.3% and 54.0%, respectively. Most adverse events were of mild or moderate severity. The only adverse event to show a dose-response relationship was a transient feeling of warmth. No clinically relevant effects on laboratory parameters were observed, and no increase in skin infection with pimecrolimus was seen. CONCLUSIONS: Oral pimecrolimus produces a dose-dependent reduction in psoriasis severity, with doses of 20 mg and 30 mg b.d. being the most effective and well tolerated.     

青鹏软膏治疗湿疹的随机、双盲、对照多中心临床观察

目的 评价青鹏软膏治疗湿疹的疗效和安全性。方法 采用随机、双盲、安慰剂对照的多中心临床试验,试验组和对照组病例数比为2：1。6个研究中心共入选湿疹患者246例,纳入疗效分析共228例,其中试验组 154例,对照组74例。试验组外用青鹏软膏,对照组外用安慰剂,均为每天2次,疗程为3周。在基线、治疗后第1、2、3周分别对瘙痒、红斑、丘疹、丘疱疹或水疱、鳞屑或结痂、浸润或苔藓样变的积分进行评价并记录不良事件。结果 用药第3周时,试验组和对照组的有效率分别为85.71%和41.89%,痊愈率分别为31.82%和12.16%,两组差异均有统计学意义（Z = 47.16、12.30,P值均 < 0.01）。试验组和对照组不良事件发生率分别为2.48%和2.56%,差异无统计学意义（χ2 = 0,P > 0.05）。结论 青鹏软膏治疗轻中度湿疹时疗效显著,起效快,安全性较高。     

前列泌尿栓治疗慢性前列腺炎多中心双盲阳性药对照试验研究

目的:评价前列泌尿栓治疗慢性前列腺炎的有效性和安全性。方法:多中心、随机、双盲、阳性药对照临床试验设计。480例湿热瘀血蕴阻型慢性前列腺炎患者按3∶1的比例随机分为治疗组、阳性对照组。治疗组360例,应用前列泌尿栓,肛内给药,1粒/次,1次/d。安慰剂对照组120例,应用前列安栓,肛内给药,1粒/次,1次/d。疗程为4周。以美国国立卫生院前列腺炎症状评分(NIH-CPSI)、慢性前列腺炎中医证候评分作为主要疗效评价指标。结果:(1)治疗4周后,治疗组和对照组CPSI评分分别为(11.88±5.28)分和(13.79±5.68)分,各组相对于基线的变化均有统计学意义(P<0.05)。治疗组和对照组治疗前后CPSI评分差值分别为(9.17±5.59)和(7.58±5.16),治疗组降幅大于对照组(P<0.05)。治疗组降低NIH-CPSI评分疗效优于对照组。(2)治疗4周后,治疗组和对照组中医证候评分分别为(8.12±4.78)分和(9.04±4.52)分,治疗组与对照组比较无统计学差异(P>0.05);治疗组和对照组治疗前后差值分别为(9.32±5.12)和(8.93±5.23),治疗组降幅与对照组比较无统计学差异(P>0.05)。(3)治疗组愈显率为49.17%,对照组为34.17%,扣除中心效应,总愈显率治疗组疗效优于对照组(P<0.05)。结论:前列泌尿栓治疗慢性前列腺炎安全、有效。     

Photochemotherapy for severe psoriasis without or in combination with acitretin: a randomized, double-blind comparison study

In a randomized, double-blind comparative study 60 patients with severe, widespread psoriasis were treated either with photochemotherapy (PUVA) alone or in combination with acitretin. Forty-eight patients completed the study; of these, 25 received placebo combined with PUVA and 23 received acitretin with PUVA. Marked or complete clearing of psoriasis occurred in 80% of the patients (20 of 25) without acitretin and in 96% of the patients (22 of 23) with adjunctive acitretin administration. The mean cumulative UVA dose given to patients in the acitretin-PUVA group was 42% less than that required for patients in the placebo-PUVA group. We conclude that acitretin substantially augments the efficacy of photochemotherapy in the treatment of severe psoriasis.     

昆仙胶囊治疗进行期寻常型银屑病的单中心随机双盲安慰剂对照临床试验研究

目的：评价昆仙胶囊治疗进行期寻常型银屑病的疗效及安全性。方法：按照入选和排除标准将进行期寻常型银屑病患者随机分成昆仙胶囊治疗组及安慰剂对照组，治疗周期为4周，采用PASI评分评价药物疗效。结果：共纳入病例60例，每组30例，治疗组脱落3例，对照组脱落1例。治疗组达到PASI 50、PASI 75、PASI 90的患者比例分别为74.1%、29.6%和14.8%，对照组各组患者均为0%，两组各PASI组均存在显著差异（P值分别为0.001，0.002，0.048）。治疗组和对照组中分别出现不良事件6例和1例。结论：昆仙胶囊治疗进行期寻常型银屑病疗效优于安慰剂。