The combination of oral acitretin and bath PUVA for the treatment of severe psoriasis

We report four patients with severe erythrodermic, pustular psoriasis, or plaque-type psoriasis, who were treated with a combination of acitretin and bath PUVA, After 4 weeks out-patient treatment, the psoriasis in all patients had improved by ≥90%. No patient had relapsed when reviewed at 3 months. No significant side-effects were seen with the combined retinoid/bath PUVA treatment. Acitretin and bath PUVA may be safely combined for the treatment of severe psoriasis.     

Efficacy of acitretin in severe psoriasis

Acitretin (Soriatane, Roche Pharmaceuticals) is an aromatic retinoid, effective in the treatment of severe psoriasis. This study highlights data from two existing clinical trials to capture PASI 50 and PASI 75 responder rates which represent a common metric used in current psoriasis clinical trials. A review of pharmacokinetics, safety and a discussion of relapse rate establish acitretin as an efficacious, convenient, oral treatment for initial and maintenance therapy of severe psoriasis.     

Consensus conference: acitretin in combination with UVB or PUVA in the treatment of psoriasis

Although adjunctive treatment with retinoids in concert with either psoralen-ultraviolet A (PUVA) or ultraviolet B (UVB) phototherapy has been a treatment option for chronic, moderate to severe plaque psoriasis for nearly two decades, acitretin-UV therapy is an underutilized therapeutic modality. According to a recent member survey by the National Psoriasis Foundation, many psoriasis patients are frustrated with available treatment options, which they perceive as ineffective, inconvenient, and/or excessively conservative. Treatment of psoriasis with acitretin in concert with UVB or PUVA is emerging as a viable clinical strategy. Compared with either acitretin or UV light monotherapy alone, the combination regimen enhances efficacy and limits treatment frequency, duration, and cumulative doses. These effects translate into care that is more effective, better tolerated, more convenient, less costly, and, perhaps, safer during long-term treatment than phototherapy alone. Drawing from an extensive literature search and the expertise of its participants, this consensus conference advances clinical recommendations as well as "clinical pearls" for health providers who treat patients with chronic, moderate to severe plaque psoriasis and suggests avenues for future research.     

阿维A治疗严重类型银屑病临床疗效观察

目的:评价阿维A治疗严重类型银屑病的临床疗效。方法:23例银屑病患者,应用阿维A治疗,成人阿维A初始剂量为0.75～1.00mg/(kg·d),平均维持剂量为10～30mg/d,平均疗程4～6周;儿童阿维A初始剂量为1.00mg/(kg·d),起效后维持量为0.10～0.20mg/(kg·d),最大不超过35.00mg/d。结果:在严重的寻常型斑块状银屑病、红皮病型银屑病、泛发性脓疱型银屑病中的有效率分别为87.5%、83.3%、100.0%。而关节病型银屑病有效率仅为50.0%。对皮肤干燥、口干、瘙痒、唇炎、掌跖脱屑以及血脂增高等不良反应进行了对症处理,结果均好转或消失。结论:阿维A治疗严重类型的银屑病疗效显著。     

The efficacy of calcipotriol + acitretin combination therapy for psoriasis: comparison with acitretin monotherapy

Background: Although the use of an oral retinoid as monotherapy is an effective treatment for psoriasis, it is usually used in combination with other topical or systemic therapies including topical corticosteroids, UVB phototherapy, psoralens + UVA (PUVA) chemotherapy and cyclosporine mainly in an effort to reduce or avoid adverse effects. Aim: To compare the efficacy of the calcipotriol + acitretin combination treatment with acitretin alone over a long period in Korean patients with psoriasis. Methods: A randomized, bilateral paired comparison was conducted involving 40 patients with psoriasis who received calcipotriol + acitretin combination therapy and 20 psoriasis patients who received acitretin alone. The initial dose of acitretin was 10 or 20 mg/day. The dose was adjusted at each visit (2, 4 and 6 weeks) in steps of 10mg according to patient responsiveness and adverse effects. The maximum dose was 40 mg/day. The treatment duration for all patients ranged from 4–52 weeks. After 12 weeks, the efficacy of therapy, according to Psoriasis Area and Severity Index scores, was assessed. At the end of the study (52 weeks), we selected patients who had achieved complete clearance and compared the duration of treatment and total dose of acitretin used in both groups. Results: After 12 weeks, 16 patients (40%) achieved complete clearance in the calcipotriol + acitretin group and 3 patients (15%) in the acitretin monotherapy group (p < 0.05). After 52 weeks, 24 patients (60%) in the calcipotriol + acitretin group and 8 patients (40%) in the acitretin monotherapy group achieved complete clearance. The duration of treatment and total dose of retinoid required to achieve clearance were slightly lower in the calcipotriol + acitretin combination group, however, this was not statistically significant. With the exception of liver enzyme elevation (which affected more patients in the acitretin monotherapy group than in the combination group), adverse effects were not significantly different. Discussion: Our results showed that calcipotriol might enhance the clinical outcome of systemic acitretin therapy. More large, well-controlled, long-term studies need to be conducted to determine whether there is indeed a beneficial effect of the addition of calcipotriol to acitretin treatment and whether this effect is maintained over long-term periods.     

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.     

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.     

Low-dose acitretin is associated with fewer adverse events than high-dose acitretin in the treatment of psoriasis

OBJECTIVE: In practice, lower dose acitretin therapy (25 mg/d) seems to be better tolerated and associated with fewer abnormalities found after laboratory testing. Here we revisit the original phase 3 trials for acitretin to evaluate the evidence for low-dose therapy producing fewer adverse effects than the 50 mg/d dosage. DESIGN: We retrospectively analyzed pooled data from 2 large pivotal trials, each including a randomized, placebo-controlled, 8-week double-blind phase followed by a 16-week open-label phase. SETTING: Multicenter pivotal trial of subjects in referral centers and private practice. PARTICIPANTS: Subjects with severe psoriasis requiring systemic therapy were recruited according to inclusion/exclusion criteria. INTERVENTION: During the double-blind phase, subjects received placebo or one of several fixed acitretin doses. Dose adjustment was allowed during the open-label phase, during which high-dose treatment was defined as a mean dosage of 50 mg/d and low-dose treatment was defined as a mean dosage of 25 mg/d. MAIN OUTCOME MEASURES: The frequency of anomalies found after laboratory testing and clinical adverse events were the outcomes of interest. RESULTS: Common adverse effects (dry skin, alopecia, rhinitis, etc) were 2 to 3 times more frequent in subjects receiving 50-mg/d acitretin than in those receiving 25 mg/d. Increases in hepatic enzymes and triglycerides in subjects receiving low-dose therapy were minimal compared with levels in those receiving high-dose therapy. CONCLUSIONS: We have shown low-dose therapy (25 mg/d) to be an effective strategy for substantially reducing acitretin-associated adverse effects. Many adverse effects associated with acitretin therapy are dose dependent and can limit the usefulness of this potentially beneficial therapy.     

Efficacy of low-dose acitretin in the treatment of psoriasis

Abstract Objectives: Clinical experience favors low doses of acitretin to reduce adverse events but still maintain efficacy. We revisited the pivotal acitretin trials to compare the efficacy of high- versus low-dose acitretin. Materials and Methods: We analyzed data from two large randomized trials which had an 8-week, double-blinded (DB), placebo-controlled phase followed by a 16-week open-label (OL) phase. During the DB phase, patients received placebo, 10, 25, 50, or 75 mg of acitretin daily. Dose adjustment was allowed during the OL phase, during which high-dose treatment was defined as approximately 50 mg/day and low-dose as approximately 25 mg/day. Primary end points were improvement of psoriasis based on investigator static global assessment (ISGA) and reduction in affected body surface area (BSA). Results: At the end of the OL phase (week 24), treatment success rates were similar among all groups (29%-33%) - with the exception of the group receiving low-dose treatment for both DB and OL phases (47% success). Decrease in BSA was also highest in this group (73% vs. 28% to 54%). Conclusion: Individualization of acitretin dosing is crucial to minimize side effects and should lead to improved adherence and efficacy. This analysis supports the utility of low-dose acitretin for psoriasis over extended treatment periods.     

阿维A及雷公藤治疗重度斑块状银屑病疗效分析

摘要：目的 观察阿维A和雷公藤治疗重度斑块状银屑病的疗效和安全性;方法：将101例斑块状银屑病患者随机分为3组,阿维A组予阿维A胶囊0.5㎎/（㎏.d）,雷公藤组予雷公藤片,2片,每日3次。联合组同时予雷公藤和阿维A治疗,剂量同单用组,三组均外用10%尿素霜,每日2次。疗程均为8周,治疗前后分别予PASI和DLQI评分。结果：3组患者的PASI和DLQI评分较治疗前明显下降（ P < 0.01）,联合组治疗后的PASI和DLQI评分较单用组比较差异显著（P < 0.05）,联合组有效率较与单用组比较差异显著（P < 0.01）,DLQI 改善率与PASI 改善率亦呈显著正相关( P < 0.01)。结论：单用和联合阿维A和雷公藤治疗重度寻常型银屑病均有疗效,但联合组疗效更好,不良反应无增加且均可耐受,联合PASI和DLQI评分评价银屑病相对更可靠,准确。     

Successful treatment of severe recalcitrant psoriasis with combination infliximab and methotrexate

Plaques of psoriasis contain increased levels of cytokines, including tumour necrosis factor-alpha (TNF-alpha), which are thought to be essential to the maintenance of the psoriatic process. We report the successful treatment of severe, recalcitrant psoriasis when infliximab (a monoclonal antibody to TNF-alpha) was used in combination with methotrexate.     

Methotrexate and ciclosporin combination for the treatment of severe psoriasis

BACKGROUND: Psoriasis is a chronic skin disease that often requires long-term therapy to control the symptoms. Combination therapies for severe psoriasis have advantages for disease control and are thought to reduce long-term side-effects. OBJECTIVE: To assess the efficacy and side-effects of methotrexate plus ciclosporin used in combination for the treatment of severe psoriasis. METHODS: In this prospective study, 20 patients were treated with the combination of methotrexate and ciclosporin. Methotrexate was given intramuscularly as a single weekly dose of 10 mg and ciclosporin at a dose of 3.5 mg/kg/day in two equally divided doses. Clinical response was assessed according to clinical outcome and the Psoriasis Area and Severity Index which were evaluated at the beginning of therapy (PASI1), after cessation of one agent (PASI2), and at the end of therapy (PASI3). RESULTS: All the patients had previously received one or more systemic treatment. There were 10 women and 10 men (mean age 44 years). The median (minimum to maximum) duration of methotrexate and ciclosporin treatments were 12.5 (4-55) and 14.0 (4-80) weeks, respectively. Median duration of combination therapy was 9.5 weeks (range 4-50). The median of previously used and end-of-study cumulative doses of methotrexate were 181.8 mg (range 0-785) and 330.8 mg (range 50-845), respectively. The median PASI scores were decreased by 77.4% (range 51.2-90.2) and 75.9% (range 10.1-100) at PASI2 and PASI3, respectively. CONCLUSION: Patients with severe psoriasis had clinically significant improvement after the initiation of combination therapy. Healing rate was decreased upon cessation of one of the medications. Short-term side-effects were minor, transient and manageable. Long-term follow-up of patients treated with this combination is needed.     

Combined treatment of psoriasis with acitretin and UVB phototherapy compared with acitretin alone and UVB alone

The administration of UVB phototherapy and low-dose acitretin (0.34-0.44 mg/kg body weight) was compared with the effect of acitretin alone and UVB phototherapy alone in 41 patients with plaque-type psoriasis. Of these patients, 32 received standard UVB phototherapy without acitretin. The other nine were treated with acitretin and the effect of UVB irradiation (Sylvania UV 21-tubes), applied to one half of the body, was assessed. Clearance was defined as 80-100% improvement and this occurred in eight out of the nine patients (89%) treated with acitretin-UVB (ReUVB) and, in two of them (23%), on the untreated side. Clearance occurred in 20 of the 32 (62.5%) patients given UVB alone. The improvement score was significantly higher for the ReUVB side than the acitretin side. Patients treated with ReUVB showed a statistically higher therapeutic score (95-100% clearance) than those receiving UVB alone. However, taking 80-100% improvement as the criterion, no significant difference was found. The number of treatments to clearance was significantly less for the patients treated with ReUVB than for the UVB (19.3 as compared with 24.9). The total UVB dose and the number of minimal erythema doses (MEDs) could be reduced by approximately 20% in the ReUVB group relative to the UVB group.     

Treatment of severe nail psoriasis with acitretin: an impressive therapeutic result

Nail psoriasis is common in adult psoriatic patients. Although several new drugs have recently been introduced for the treatment of skin psoriasis, treatment of nail psoriasis still remains a challenge. Topical treatments (e.g., corticosteroids, tazarotene, 5‐fluorouracil, calcipotriol) are the first line in the management of skin psoriasis. The efficacy of these drugs in nail disease, however, is limited, mainly due to the difficulty in penetrating the nail bed and nail matrix. In cases of nail disease resistant to topical treatment, methotrexate, ciclosporin, acitretin, or biological agents can be used. The present authors introduce a 73‐year‐old patient affected by impressive psoriatic nail disease involving all her fingernails and toenails treated by acitretin, a traditional systemic treatment. After 2 months of treatment there was a marked improvement. The clinical improvement of the nails was progressive and 6 months later it was stable and satisfactory. The remarkable response to treatment in this case suggests that oral acitretin, in association to urea nail lacquer, might be useful in the management of disabling severe nail psoriasis even in absence of severe cutaneous involvement.     

小剂量阿维A与MTX联合治疗重症寻常型银屑病随机对照研究

目的:观察小剂量阿维A与甲氨蝶呤(MTX)联合治疗重症寻常型银屑病的疗效与不良反应。方法:观察组:阿维A0.3mg(kg·d),MTX2.5mg,12h1次,每周连服3次,辅以叶酸5mgd,维生素E300mgd,用药6周。对于6周内临床治愈的病人,先停用MTX,阿维A减半维持治疗2周,停药。对照组1:阿维A0.3mg(kg·d),3～5d后加至0.5mg(kg·d),叶酸和维生素E同观察组,用药6周;对照组2:MTX5mg,12h1次,每周连服3次,叶酸和维生素E同观察组,用药6周。结果:观察组、对照组1和对照组2的有效率分别为96.23%、65.54%和66.67%。三组相比有显著性差异(χ2=9.97,P<0.01)。三组间不良反应发生率分别为11.32%、33.33%和27.27%,有显著性差异(χ2=8.67,P<0.05)。结论:小剂量阿维A与小剂量MTX联合治疗重症寻常型银屑病疗效好,不良反应发生率低。     

阿维A治疗斑块状银屑病临床疗效观察

目的:观察阿维A治疗中、重度斑块状银屑病的疗效.方法:将中、重度斑块状银屑病患者随机分成两组,分别给予阿维A和海棠合剂治疗,疗程均为8周,以银屑病面积和严重度指数(PASI)和皮肤病生活质量指数(DLQI)作为观察指标,比较两种药物的疗效.结果:治疗后,两组患者的PASI评分和DLQI评分与治疗前比较均显著下降(P＜0.01),但PASI改善率和DLQI改善率两组间比较差异无统计学意义,PASI50和PASI75有效率亦无统计学意义(P＞0.05).结论:阿维A治疗中、重度斑块状银屑病有效.     

阿维A治疗重症银屑病的系统评价

目的系统评价阿维A治疗重症银屑病的有效性与安全性。方法计算机检索MEDLINE、Cochrane图书馆、EM-base、CBM、CNKI和万方数字化期刊全文数据库,语种限于英、中文,根据纳入与排除标准筛选文献,纳入阿维A治疗重症银屑病的随机对照试验（Randomized Controlled Trial,RCT）。采用RevMan5．0软件进行Meta分析。结果共纳入6个RCT,包括497例患者,其中试验组338例,对照组159例。总体Meta分析结果显示常规剂量阿维A口服（≥30mg／d）与对照组疗效无统计学差异（[RR=2．15,95％ci（o．72,6．42）],P〉0．05）。亚组分析结果提示无论常规量阿维A单独口服或联合其它药物疗效均与对照组无统计学差异;阿维A单独口服10mg／d及25mg／d时,其疗效均差于依曲替酯口服（[RR=0．62,95％CI（O．43,0．89）],P〈0．05及[RR=0．50,95％CI（0．33,0．77）],P〈0．05）;阿维A联合中波紫外线治疗疗效优于安慰剂对照组（[RR=2．24,95％CI（1．44,3．48）],P〈0．05）。阿维A治疗最常见不良反应为唇炎、皮肤干燥、脱屑、脱发、甲脆,还包括一过性的血脂升高、肝功能异常。结论阿维A单独口服或联合其它药物治疗重症银屑病的疗效不确定,阿维A联合中波紫外线治疗重症银屑病可能有效。阿维A治疗不良反应轻微。由于本系统评价存在局限性,结论尚需高质量、大规模、多中心、大样本的RCT加以证实．