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.     

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.     

Evaluation of the efficacy,safety, and side effects of secukinumab in patients with moderate-to-severe psoriasis: real-world data from a retrospective multicenter study

BackgroundClinical studies have demonstrated that IL-17A inhibition with secukinumab is effective for clearing the skin of patients with psoriasis and has a favorable safety profile.ObjectiveThe authors aim to determine whether secukinumab is effective and safe for the treatment of moderate-to-severe chronic psoriasis based on clinical experience with this drug.MethodThe authors conducted a multicenter retrospective study in nine referral centers and included patients with psoriasis who had received secukinumab between March 2018 to November 2020. Data on demographic characteristics, Psoriasis Area and Severity Index (PASI) scores, and previous treatments were collected from medical records. Patients were evaluated at 12, 24, and 52 weeks with respect to response to treatment and side effects.ResultsIn total, 229 patients were recruited for the study. A PASI score improvement of ≥90 points over the baseline was achieved by 79%, 69.8%, and 49.3% of patients at weeks 12, 24, and 52, respectively. The most common adverse events wereCandida infections and fatigue. In total, 74 (32%) patients discontinued treatment by week 52, including due to adverse events, or secondary ineffectiveness.Study limitationsRetrospective design.ConclusionsThese findings suggest that secukinumab therapy is reasonably effective in patients with moderate-to-severe psoriasis. Comorbidities and time length of the disease can affect the response to treatment. The rates of adverse events were high in this patient population.     

钙泊三醇倍他米松软膏外用治疗寻常性银屑病的随机、双盲、对照研究

目的 探讨钙泊三醇倍他米松软膏外用治疗稳定期寻常性银屑病患者的临床疗效和安全性。方法 随机、双盲、阳性药物平行对照、多中心临床试验,入组320例寻常性银屑病患者,随机纳入试验组或对照组,疗程4周。试验组早晨外用模拟剂软膏基质,晚间外用钙泊三醇倍他米松软膏;对照组早晚单用卡泊三醇软膏。于首次用药后第1、2、4周观察临床疗效及安全性。结果 治疗4周后试验组PASI评分较基线下降百分比（79.23%）大于对照组（70.43%）,两组比较,P < 0.01;且在治疗1周后的疗效优于对照组。治疗4周后,PASI评分较基线下降≥75%的患者频数百分比比较,试验组有效率为73.03%,对照组为48.32%,P < 0.01,两组差异有统计学意义。治疗1、2、4周后试验组靶皮损红斑、浸润、鳞屑单独积分以及皮损总面积百分比等指标改善方面均优于对照组。320例受试者中不良事件发生率为18.1%,不良反应发生率为13.1%,两组间差异无统计学意义。药物不良反应主要为与皮肤有关的轻中度反应如瘙痒、毛囊炎、红斑等。结论 钙泊三醇倍他米松软膏治疗稳定期寻常性银屑病患者具有起效快、疗效好和用药方便、相对安全的特点。     

Therapy of psoriasis with retinoid plus PUVA: Clinical and histologic data

Summary In a group of 40 patients suffering from wide-spread psoriasis oral administration of a retinoid (Ro 10-9359) was followed by PUVA therapy. The clearance rate was increased by 30% as compared to PUVA alone. Except for cheilitis no side effects were seen. Histological analysis in 20 patients before, during and after therapy revealed an intensification of psoriatic tissue changes after retinoid treatment. Loss of corneal layers, massive exoserosis, and neutrophil migration were prominent features. Mitotic counts were not increased by the pretreatment. The increased susceptibility of diseased skin to PUVA as produced by this drug appears to be based on several factors related to the tissue changes revealed by histology.Presented at the Niels-Stenson-Symposion, Appenrade, Denmark, October 28, 1978     

Oral liarozole in the treatment of palmoplantar pustular psoriasis: a randomized, double-blind, placebo-controlled study

BACKGROUND: Palmoplantar pustular psoriasis (PPP) is a chronic, relapsing condition often recalcitrant to therapy. Synthetic retinoids have been found to be efficacious in the treatment of PPP, but their use is limited by side-effects. Liarozole is an imidazole-like compound that inhibits the retinoic acid (RA) 4-hydroxylase-mediated breakdown of all-trans RA, causing elevation of plasma and cutaneous levels of RA. Thus liarozole acts as a retinoid-mimetic drug. Liarozole has already been found to be effective in the treatment of retinoid-responsive conditions such as chronic plaque psoriasis and ichthyoses. OBJECTIVES: To assess the efficacy and side-effect profile of liarozole in the treatment of PPP. METHODS: We performed a double-blind, randomized, placebo-controlled trial of oral liarozole 75 mg twice daily for 12 weeks in the treatment of PPP. The trial was conducted at two centres and involved 15 patients. RESULTS: Using the PPP Area and Severity Index we found a statistically significant (P = 0.02) improvement in PPP in subjects on liarozole (median 3, range 1.8-14.1) as compared with placebo (median 12.1, range 5-18) by the end of the treatment phase. There was also a statistically significant difference (P = 0.006) in the number of fresh pustules after treatment for the two study groups (liarozole median 2, range 0-18; placebo median 38, range 2-75). The severity of disease (on a scale of 0-8) between the two groups was significantly different at the end of treatment (liarozole median 1, range 1-5; placebo median 3, range 2-6; P = 0.04). No patients withdrew from the trial because of adverse events. The most commonly reported side-effects were pruritus, cheilitis and xerosis but these were rarely severe and resolved rapidly on discontinuation of treatment. Laboratory results, including haematology, liver function tests and serum cholesterol and triglycerides were not significantly different between the liarozole and placebo groups. CONCLUSIONS: The results of this pilot study suggest that liarozole 75 mg twice daily is an effective and well-tolerated therapy for PPP. In addition, the pharmacokinetics of liarozole may help to circumvent side-effects associated with synthetic retinoids and allow its use in premenopausal women.     

Topical becocalcidiol for the treatment of psoriasis vulgaris: a randomized, placebo-controlled, double-blind, multicentre study

BACKGROUND: Becocalcidiol is a vitamin D(3) analogue which has not caused hypercalcaemia or significant irritation in preclinical trials. OBJECTIVES: To evaluate the efficacy and safety of two dosing regimens of becocalcidiol ointment (low dose = 75 microg g(-1) once daily for 8 weeks; high dose = 75 microg g(-1) twice daily for 8 weeks) in the treatment of plaque-type psoriasis. METHODS: One hundred and eighty-five subjects with chronic plaque-type psoriasis affecting 2-10% of their body surface area took part in a multicentre, double-blind, parallel-group, vehicle-controlled, randomized controlled trial comparing topical application of placebo, becocalcidiol 75 microg g(-1) once daily (low dose) or becocalcidiol twice daily (high dose) for 8 weeks. Main outcomes included Physician's Static Global Assessment of Overall Lesion Severity (PGA) score; Psoriasis Symptom Severity (PSS) score; adverse events; and laboratory assessment. RESULTS: In the intent-to-treat population at week 8, high-dose becocalcidiol was statistically superior to vehicle [P = 0.002; 95% confidence interval (CI) 6.7-32.2], with 16 of 61 (26%) subjects achieving a PGA score of clear or almost clear. Greater improvement in PSS score was seen with high-dose becocalcidiol than with vehicle, but this result did not quite achieve statistical significance (P = 0.052; 95% CI -16.2 to 0.1). In all groups, therapy was safe and well tolerated, with fewer subjects experiencing irritation than is reported in studies using calcipotriol. CONCLUSIONS: Treatment with high-dose topical becocalcidiol for 8 weeks led to almost or complete clearing of moderate plaque-type psoriasis in over a quarter of patients. Therapy was safe and well tolerated.     

A randomized, double-blind, placebo-controlled study to evaluate the addition of methotrexate to etanercept in patients with moderate to severe plaque psoriasis

Background Etanercept plus methotrexate combination therapy has not been adequately investigated in psoriasis. Objectives To evaluate etanercept plus methotrexate vs. etanercept monotherapy in patients with moderate to severe plaque psoriasis who had not failed prior methotrexate or tumour necrosis factor‐inhibitor therapy. Methods Patients received etanercept 50 mg twice weekly for 12 weeks followed by 50 mg once weekly for 12 weeks and were randomized 1 : 1 to receive methotrexate (7·5–15 mg weekly) or placebo. The primary endpoint was the proportion of patients achieving ≥75% improvement in Psoriasis Area and Severity Index (PASI 75) at week 24. Results In total, 239 patients were enrolled in each arm. PASI 75 was significantly higher at week 24 for the combination therapy group compared with the monotherapy group (77·3% vs. 60·3%; P < 0·0001). Other PASI improvement scores at week 12 [PASI 75, 70·2% vs. 54·3% (P = 0·01); PASI 50, 92·4% vs. 83·8% (P = 0·01); and PASI 90, 34·0% vs. 23·1% (P = 0·03)] showed similar results as did week 24 PASI 50 (91·6% vs. 84·6%; P = 0·01) and PASI 90 (53·8% vs. 34·2%; P = 0·01). Significantly more patients receiving combination therapy than monotherapy had static Physician’s Global Assessment of clear/almost clear at week 12 (65·5% vs. 47·0%; P = 0·01) and week 24 (71·8% vs. 54·3%; P = 0·01). Adverse events (AEs) were reported in 74·9% and 59·8% of combination therapy and monotherapy groups, respectively; three serious AEs were reported in each arm. Conclusions Combination therapy with etanercept plus methotrexate had acceptable tolerability and increased efficacy compared with etanercept monotherapy in patients with moderate to severe psoriasis.     

Immunologic implications of PUVA therapy in psoriasis vulgaris

Summary During the combined effects of psoralen and UVA irradiation (PUVA therapy) a significant decrease (P<0.005 in T cells has been noted in 10 psoriasis patients and 10 healthy controls especially after four exposures. Based on the fact that the total number of circulating lymphocytes of the patients and the PUVA-treated healthy controls remained within the normal range, this decrease may be due to temporary physicochemical changes of the membranes of these cells but not to T cell lysis. After eight exposures these decreased T cell values returned to starting range. The starting T cell range in psoriasis patients is significantly lower (P<0.005) compared to that of healthy controls.It is of importance that before PUVA therapy in all the patients antibodies reactive with a basal cell nuclear antigen belonging to the four main Ig classes (IgM, IgD, IgE, and IgA) could be removed from the membrane of circulating lymphocytes by means of acid elution. In contrast, mainly the IgA antinuclear basal cell antibody could be eluted from circulating PMN leukocytes in the patients under investigation. After eight PUVA exposures, however, corresponding antibodies, belonging to the three main Ig classes (IgM, IgD and IgE) could also be eluted from the membranes of circulating PMN-leukocytes of the same patients. This implies an exchange of molecules during photochemotherapy. Finally, it could be shown that after effective PUVA therapy antinuclear basal cell antibodies of the psoriasis patients under study were reactive not only with the nuclei of the basal cell layer but also with almost all the nucleic of the epidermis of the uninvolved and lesional skin. The latter finding points to the fact that PUVA treatment causes at least antigenic changes of nuclear proteins in all the nuclei of the epidermis of the PUVA treated skin. Moreover, inflammatory cells with Fab fragments within the cells present in the lesional skin before PUVA disappear during this treatment.Based on a poster session presented at the occasion of the seventh joint meeting of the ESDR, Amsterdam, The Netherlands, May 1977     

XP-828l in the treatment of mild to moderate psoriasis: randomized, double-blind, placebo-controlled study

BACKGROUND: XP-828L, a protein extract obtained from sweet whey, has demonstrated potential benefit for the treatment of mild to moderate psoriasis in an open-label study. OBJECTIVE: To study in a randomized, double-blind, placebo-controlled study the safety and efficacy of XP-828L in the treatment of mild to moderate psoriasis. DESIGN: XP-828L 5 g/d (group A, n = 42) or placebo (group B, n = 42) was given orally for 56 days followed by XP-828L 5 g/d in group A and by XP-828L 10 g/d in group B for an additional 56 days. RESULTS: Patients receiving XP-828L 5 g/d for 56 days had an improved Physician's Global Assessment (PGA) score compared with patients under placebo (p < .05). Considering the data of group A only, the PGA score improved from day 1 to day 56 (p < .01); the Psoriasis Area and Severity Index score improved as well, but to a lesser extent (p < .05). CONCLUSION: Oral administration of 5 g/d XP-828L compared with a placebo significantly improved the PGA score of patients with mild to moderate psoriasis.     

【开放获取】丙酸氟替卡松乳膏单独或联合卡泊三醇软膏治疗轻中度斑块状银屑病的随机自身对照研究

【摘要】 目的 评价0.05%丙酸氟替卡松乳膏单独应用及与0.005%卡泊三醇软膏联合应用治疗轻中度斑块状银屑病的短期疗效和安全性。方法 2020年10月至2021年1月,于北京友谊医院对30例轻中度斑块状银屑病患者采用随机、开放、自身对照临床研究,一侧肢体皮损处早上外用0.005%卡泊三醇软膏、晚上外用0.05%丙酸氟替卡松乳膏（联合用药组）,对侧肢体皮损处每日外用2次0.05%丙酸氟替卡松乳膏（丙酸氟替卡松组）,疗程4周。分别于治疗前、治疗1、2、4周随访,采集静态临床医生整体评估（sPGA）、银屑病面积和严重程度指数（PASI）等临床指标,并记录不良事件。采用重复测量的方差分析、多变量方差分析、Mann-Whitney U秩和检验和独立样本t检验进行疗效和安全性评价。结果 治疗前,两组sPGA评分、PASI评分差异均无统计学意义（均P > 0.05）。治疗1周,丙酸氟替卡松组sPGA（1.10 ± 0.31）分、PASI评分（1.05 ± 0.51）分显著低于联合用药组［sPGA（1.73 ± 0.45）分,PASI评分（1.38 ± 0.69）分,F = 40.74、4.38,均P < 0.05］;治疗2、4周,联合用药组sPGA为（0.83 ± 0.46）、（0.23 ± 0.43）分,PASI评分为（0.53 ± 0.47）、（0.23 ± 0.50）分,均显著低于丙酸氟替卡松组（F = 4.88、56.14、15.21、26.36,均P < 0.05）。治疗1周,丙酸氟替卡松组浸润/肥厚严重程度评分显著低于联合用药组（U = 165.00,P < 0.05）;治疗2、4周,联合用药组红斑、鳞屑严重程度评分均显著低于丙酸氟替卡松组（U = 540.00、765.00、825.00、795.00,均P < 0.05）。结论 单用0.05%丙酸氟替卡松乳膏治疗银屑病起效快,0.05%丙酸氟替卡松乳膏与0.005%卡泊三醇软膏联合用药治疗2、4周效果更好,两种方法安全性均可。     

A novel micronutrient supplement in skin aging: a randomized placebo-controlled double-blind study

Background Skin aging, a combination of intrinsic and environmentally induced processes, predominantly ultraviolet (UV) light from the sun, results in characteristic tissue alterations, such as the degradation of collagen and the formation of visible fine lines and wrinkles. Objective To test the efficacy and safety of a novel micronutrient supplement (Estime^®) in skin aging. Methods A 4‐month randomized double‐blind controlled study including 40 subjects where the supplement was tested against placebo for 3 months followed by a 1‐month supplement‐free period for both groups to assess lasting effects. Efficacy measurements included skin surface evaluation, ultrasound measurement of sun‐exposed and protected areas of the skin (back of the hand and ventral forearms, respectively), and photographic assessment. Results All investigated parameters showed a continuous and significant improvement in the active group during the 3 months of supplementation as compared to placebo. Photographs showed visible improvement of the overall skin appearance and reduction of fine lines. Ultrasound measurements showed an increase in dermis density of up to 78% in the active group (P < 0.0001). The final assessment after 1 month without supplementation showed no further improvements, but a slight decrease was observed in most improved parameters. No treatment‐related side effects were reported. Conclusion The study demonstrated that the supplement appears to be effective and safe as an oral supplement to protect the skin and support its repair process. Recommendations are made for further evaluations.     

A double-blind comparison of acitretin and etretinate in combination with bath PUVA in the treatment of extensive psoriasis

Thirty-four patients with extensive psoriasis were treated in a double-blind parallel fashion with either acitretin plus bath PUVA (trimethylpsoralen bath + UVA) or etretinate plus bath PUVA. Each group consisted of 17 patients. The dose of retinoid was 40 mg/day during the 2-week monotherapy phase and subsequently 20 mg/day during the combination treatment. Bath PUVA was given three times a week starting with a UVA dose of 0.06 J/cm2. Remission (greater than 90% improvement) was achieved in all patients in 6-10 weeks. There were no significant differences in clinical response between the two groups; the mean +/- SD PASI score (psoriasis area and severity index) before treatment was 22.6 +/- 7.1 in the acitretin-PUVA group and 19.4 +/- 7.8 in the etretinate-PUVA group. The corresponding figures after treatment were 0.6 +/- 0.6 and 1.0 +/- 0.5, respectively. Side-effects related to retinoid treatment were frequent in both groups but they were usually mild and well-tolerated. There was only one case of diffuse alopecia after 8 weeks in the etretinate-PUVA group. Scaling of the palms and soles was seen in six patients in the acitretin-group but only in two patients in the etretinate-group. Triglycerides were elevated in about half of the patients in both groups. The present study shows that acitretin is as effective as etretinate in the combination with bath PUVA.     

Dead sea bath salt for the treatment of psoriasis vulgaris: a double-blind controlled study

Back-ground The beneficial effect of the Dead Sea (DS) area in psoriasis is attributed in part to the DS water, which has a high content of minerals, Aim The aim of the study was 10 evaluate the sole therapeutic effect of DS salt in psoriasis. Patients and Methods Thirty patients wild psoriasis vulgaris, involving >15% body area, were included in the study, which was conducted in a double-blind controlled manner. Treatment consisted of once daily baths, heated lo 35°C, of 20 min duration, for 3 weeks, of cither DS bath salt (group I) or common salt (group II). Clinical evaluation was based on Psoriasis Area and Severity Index (PASI) score determination before and after treatment Results Twenty-five patients 113 in group 1 and I 2 in group II) terminated the treatment protocol. In both groups, treated by US hath salt and common salt, respectively, the mean PASI score before treatment (18.6, ± 9.4 and 15.7 ± 7.1. respectively) decreased significantly al the end of the treatment (11.4 ± 6.1 and 11.4± 6.6, respectively). The mean percentage reduction of PASI score at the end of the treatment regimen, was higher in patients treated with IDS bath salt (34.8%) compared to patients treated with common salt (27.5%) (P > 0.05). The mean percentage reduction a month after termination of the treatment protocol was higher in patients treated with DS hath salt (43.6%) than in those treated with common salt (24%) (P > 0.05). Conclusions The present study implies a beneficial effect to bathing wish either DS hath salt or common salt as a sole therapy for psoriasis vulgaris. However, we observed an enhanced beneficial effect of DS hath salt compared to common salt.     

Ustekinumab治疗中重度斑块状银屑病的系统评价

银屑病是一种慢性复发性炎症性皮肤病,在我国患病率约0.123％［１］,因其慢性、顽固难愈、复发率高,成为皮肤科领域重点研究防治的疾病之一。Ustekinumab在2009年获准治疗中重度斑块状银屑病,它可与人体白介素12/白介素23的p40亚单位结合,抑制其生物活性,达到治疗银屑病的作用［2］,但其疗效结论尚不统一,且缺乏长期有效性及安全性评价［3］。我们检索文献,对Ustekinumab治疗中重度斑块状银屑病的疗效和安全性进行系统评价……     

Infliximab treatment results in significant improvement in the quality of life of patients with severe psoriasis: a double-blind placebo-controlled trial

Background Psoriasis is a chronic disease that significantly diminishes the health‐related quality of life (HRQOL). Infliximab is a chimeric, tumour necrosis factor α monoclonal antibody that has been shown to improve the signs and symptoms of plaque psoriasis. Objectives The objective of this study was to evaluate the effect of infliximab induction therapy on the HRQOL of patients with severe plaque psoriasis. Methods In this double‐blind, placebo‐controlled trial, 249 patients were randomly assigned to receive intravenous infusions of 3 or 5 mg kg^?1 of infliximab or placebo and were treated at weeks 0, 2 and 6. Patients completed the Dermatology Life Quality Index (DLQI) at baseline and week 10. Results Infliximab induction therapy resulted in a substantial improvement in HRQOL. At week 10, patients in the infliximab 3‐ and 5‐mg kg^?1 groups showed a median percentage improvement in DLQI scores of 84·0% and 91·0%, respectively, compared with 0% in the placebo group (P < 0·001). The median decrease from baseline in DLQI score at week 10 was 8·0 and 10·0 for the 3 and 5 mg kg^?1 infliximab groups, respectively, compared with 0 in the placebo group (P < 0·001). Thirty‐three per cent and 40% of patients in the 3 and 5 mg kg^?1 infliximab groups, respectively, had a DLQI score of 0 at week 10, compared with 2% in the placebo group (P < 0·001). There was a strong correlation between the percentage change from baseline at week 10 in Psoriasis Area and Severity Index (PASI) scores and the percentage change in DLQI scores during the same period (Spearman's correlation, 0·61, P < 0·001). When the infliximab and placebo treatment groups were combined, patients with at least 75% improvement in PASI scores between baseline and week 10 had a greater mean improvement in DLQI scores (81%) than those with 50–75% improvement in PASI during the same period (60%). Conclusions Infliximab induction therapy resulted in significant improvement in HRQOL in patients with severe psoriasis.