Once weekly administration of etanercept 50 mg is efficacious and well tolerated in patients with moderate-to-severe plaque psoriasis: a randomized controlled trial with open-label extension

Background In previous studies, etanercept 25 mg twice weekly (BIW) or 50 mg BIW significantly reduced disease severity in patients with plaque psoriasis and demonstrated a favourable safety profile. Objectives To assess the efficacy and safety of etanercept 50 mg administered once weekly (QW) compared with placebo in patients with moderate‐to‐severe plaque psoriasis over 24 weeks. Methods This study was conducted in two parts: (i) a 12‐week, double‐blind, placebo‐controlled phase, in which patients received etanercept 50 mg QW or placebo QW; and (ii) a 12‐week, open‐label extension phase, in which all patients received etanercept 50 mg QW. Primary endpoint was a 75% or greater improvement from baseline in the Psoriasis Area and Severity Index (PASI 75) at week 12. Secondary endpoints included percentage PASI improvement and Physician’s Global Assessment (PGA). Results One hundred and forty‐two patients were analysed in the double‐blind phase; 126 patients entered the open‐label phase. At week 12, significantly more patients receiving etanercept 50 mg QW (37·5%) achieved PASI 75 response than patients receiving placebo (2·2%; P < 0·0001). At week 24, 71·1% in the etanercept–etanercept group and 44·4% in the placebo–etanercept group achieved PASI 75. Mean percentage of PASI improvement from baseline was 55·4% with etanercept vs. 9·4% worsening with placebo at week 12 (P < 0·0001), with 77·4% and 57·7% improvement in the etanercept–etanercept and placebo–etanercept groups at week 24. A PGA score of 0–1 (clear–almost clear) was achieved by 64% and 42% in the etanercept–etanercept and placebo–etanercept groups at week 24, respectively. Etanercept 50 mg QW was well tolerated. No deaths, serious infections, opportunistic infections (including tuberculosis), demyelinating disorders, malignancies or new safety signals were reported. Conclusions Nearly three‐quarters of patients with moderate‐to‐severe psoriasis receiving etanercept 50 mg QW achieved significant improvement in disease severity over 24 weeks. This study also showed a favourable tolerability and safety profile with etanercept 50 mg QW.     

Patient-reported outcomes of psoriasis improvement with etanercept therapy: results of a randomized phase III trial

BACKGROUND: Etanercept, a soluble tumour necrosis factor receptor, lessens the severity of psoriasis as measured by physician-reported clinical outcomes. Equally important is the patient perspective on the effect of etanercept therapy on daily life. OBJECTIVES: To assess patient-reported outcomes (PROs) in patients with psoriasis receiving etanercept therapy. METHODS: In this multinational, randomized, phase III trial, patients with psoriasis received placebo (n = 193), etanercept 50 mg per week (n = 196) or etanercept 50 mg twice weekly (n = 194) during the initial 12-week, double-blind period. Thereafter, all patients received open-label etanercept (50 mg per week). The following PROs were assessed: Dermatology Life Quality Index (DLQI), Short Form-36 Health Survey (SF-36), patient rating of pruritus, and patient global assessment of psoriasis. RESULTS: At week 12, DLQI total score improved by 65-70% in patients receiving etanercept compared with 6% in patients receiving placebo (P < 0.0001), and improvement in DLQI was clinically meaningful (> or = 5-point improvement or 0 score) for 72-77% of patients receiving etanercept therapy. All DLQI and SF-36 subscales and the SF-36 physical and mental component summary scores demonstrated significantly greater improvement with etanercept therapy than with placebo, illustrating that etanercept benefits patients with psoriasis across multiple domains that contribute to health-related quality of life. With etanercept therapy, distributions of patient ratings of pruritus and global assessment of disease shifted from moderate to severe (baseline) to minimal to good (week 12). Etanercept-induced benefits of PROs were maintained for patients who reduced their dose after 12 weeks. CONCLUSIONS: Etanercept therapy improves PROs in patients with psoriasis and makes a meaningful difference to their lives. These results support the efficacy profile of physician-reported clinical measures while providing a more complete understanding of the benefits experienced by patients with psoriasis treated with etanercept.     

Efficacy and safety results from the randomized controlled comparative study of adalimumab vs. methotrexate vs. placebo in patients with psoriasis (CHAMPION)

BACKGROUND: Biologic therapies such as adalimumab, a tumour necrosis factor antagonist, are safe and effective in the treatment of moderate to severe chronic plaque psoriasis. OBJECTIVES: To compare a biologic agent with methotrexate, a traditional systemic agent, to define clearly the role of biologics in psoriasis. METHODS: Patients with moderate to severe plaque psoriasis were randomized to adalimumab (80 mg subcutaneously at week 0, then 40 mg every other week, n=108), methotrexate (7.5 mg orally, increased as needed and as tolerated to 25 mg weekly; n=110) or placebo (n=53) for 16 weeks. The primary efficacy endpoint was the proportion of patients achieving at least a 75% improvement in the Psoriasis Area and Severity Index (PASI 75) after 16 weeks. Safety was assessed at all visits through week 16. RESULTS: After 16 weeks, 79.6% of adalimumab-treated patients achieved PASI 75, compared with 35.5% for methotrexate (P<0.001 vs. adalimumab) and 18.9% for placebo (P<0.001 vs. adalimumab). Statistically significantly more adalimumab-treated patients (16.7%) than methotrexate-treated patients (7.3%) or placebo-treated patients (1.9%) achieved complete clearance of disease. The response to adalimumab was rapid, with a 57% improvement in mean PASI observed at week 4. Adverse events were similar across treatment groups. Adverse events leading to study discontinuation were greatest in the methotrexate group, primarily because of hepatic-related adverse events. CONCLUSIONS: After 16 weeks, adalimumab demonstrated significantly superior efficacy and more rapid improvements in psoriasis compared with either methotrexate or placebo.     

Improvement in quality of life with infliximab induction and maintenance therapy in patients with moderate-to-severe psoriasis: a randomized controlled trial

BACKGROUND: Psoriasis has a well-documented, markedly negative effect on patient quality of life. OBJECTIVES: To evaluate the impact of long-term infliximab maintenance therapy on health-related quality of life (HRQoL) in patients with psoriasis. METHODS: The Dermatology Life Quality Index (DLQI) and 36-item Short Form Health Survey (SF-36) were administered as part of the pivotal double-blind, placebo-controlled efficacy and safety EXPRESS study of infliximab in chronic plaque psoriasis. In total, 378 patients with moderate-to-severe psoriasis were enrolled at 32 centres in Europe and Canada. Patients were randomized to receive either placebo or infliximab 5 mg kg(-1) induction at weeks 0, 2 and 6 followed by maintenance every 8 weeks; placebo patients crossed over at week 24 to receive the infliximab induction and maintenance regimen. RESULTS: At week 10, infliximab-treated patients had significantly greater improvement in DLQI scores (P < 0.001) and SF-36 physical and mental component summary scores (P < 0.001) than placebo-treated patients. Significant improvement (P < 0.001) was also seen in all eight SF-36 subscales, and was greatest for the "Bodily Pain" and "Social Functioning" scales. Significant improvement in HRQoL persisted with maintenance infliximab treatment at week 24 (P < 0.001), with patients achieving a Psoriasis Area and Severity Index score of 0 reporting the greatest benefit. Treatment-related HRQoL improvement remained substantial at week 50. CONCLUSIONS: Infliximab induction and maintenance regimens resulted in rapid, substantial, sustained and clinically meaningful improvement in both dermatology-specific and general quality of life indices in patients with psoriasis, with total clearance resulting in maximum improvement.     

The effect of inositol supplements on the psoriasis of patients taking lithium: a randomized, placebo-controlled trial

BACKGROUND: Lithium carbonate is the most widely used long-term treatment for bipolar affective disorders, but its ability to trigger and exacerbate psoriasis can become a major problem in patients for whom lithium is the only treatment option. Inositol depletion underlies the action of lithium in bipolar affective disorders and there are good theoretical reasons why the use of inositol supplements might be expected to help this group of patients. OBJECTIVES: To determine whether inositol supplements improve the psoriasis of patients on lithium therapy. METHODS: Fifteen patients with psoriasis, who were taking lithium, took part in a randomized, double-blind, placebo-controlled, crossover clinical trial comparing the effect of inositol supplements with those of a placebo (lactose). Changes in the severity of their psoriasis were measured by Psoriasis Area and Severity Index scores recorded before and after the different courses of treatment. The effect of inositol supplements on the psoriasis of 11 patients who were not taking lithium was evaluated in the same way. RESULTS: The inositol supplements had a significantly beneficial effect on the psoriasis of patients taking lithium. No such effect was detected on the psoriasis of patients not on lithium. CONCLUSIONS: The use of inositol supplements is worth considering for patients with intractable psoriasis who need to continue to take lithium for bipolar affective disorders.     

Two years of experience with etanercept in recalcitrant psoriasis

BACKGROUND: The safety and efficacy of etanercept have been demonstrated in patients with rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis. Placebo-controlled trials have indicated the efficacy of etanercept in moderate to severe psoriasis. OBJECTIVES: To observe the efficacy and safety profile of etanercept in patients with severe psoriasis resistant to other systemic agents over a 2-year period. METHODS: In this retrospective study, 49 patients were treated with etanercept between March 2004 and March 2006. All patients were screened for tuberculosis with tuberculin test and a chest X-ray. Thirty-nine patients started on etanercept 25 mg twice weekly (BIW) and 10 started at 50 mg BIW when judged to be clinically indicated. In 19 of those on 25 mg BIW, the dose was increased to 50 mg BIW because of poor response and psoriasis flaring. Response to treatment was assessed by Psoriasis Area and Severity Index (PASI) and static Physician Global Assessment (PGA). Patients were reviewed at 8-week intervals, when clinical response and adverse effects were noted. RESULTS: Forty-four patients (90%) had chronic plaque psoriasis, two (4%) were suberythrodermic, one (2%) had palmoplantar pustular psoriasis and two (4%) had acrodermatitis continua of Hallopeau. At least 75% reduction in PASI was achieved in 47% of patients at week 24 and 66% at week 48. At week 24, 44% had a PGA score of excellent, and at week 48, 58% scored excellent. In 12 who cleared, etanercept was stopped. Ten of these relapsed and etanercept was recommenced, while two remained in remission (mean 12.5 weeks). One patient developed extrapulmonary tuberculosis. CONCLUSIONS: Etanercept was effective in severe psoriasis recalcitrant to other systemic medication. The drug was well tolerated. Development of tuberculosis in one patient underlines the need for rigorous tuberculosis screening.     

Efficacy of sirolimus (rapamycin) administered concomitantly with a subtherapeutic dose of cyclosporin in the treatment of severe psoriasis: a randomized controlled trial

BACKGROUND: The identification of a highly potent immunosuppressive/antiproliferative agent with an acceptable toxicity profile has long been a goal for the management of severe plaque psoriasis. OBJECTIVES: To investigate the efficacy and safety of sirolimus (Rapamune) for severe psoriasis when given alone or in association with cyclosporin. METHODS: In a randomized, double-blind, eight parallel group, pilot study in 24 out-patient centres in seven European countries, 150 patients, 18 years and older, with severe chronic plaque psoriasis were given sirolimus 0.5, 1.5 and 3.0 mg m(-2) daily for 8 weeks, either alone or in association with a subtherapeutic dose of cyclosporin (1.25 mg kg(-1) daily). Cyclosporin 5 mg kg(-1) daily was the positive control and cyclosporin 1.25 mg kg(-1) daily the negative control. The primary efficacy variable was the mean percentage reduction in Psoriasis Area and Severity Index (PASI). Safety assessments included monitoring of adverse events, clinical laboratory parameters and sirolimus/cyclosporin blood concentrations. RESULTS: The greatest mean percentage decreases in PASI were seen with cyclosporin 5.0 mg kg(-1) daily (70.5%) and with sirolimus 3.0 mg m(-2) daily + cyclosporin 1.25 mg kg(-1) daily (63.7%). Both groups demonstrated significantly better results than cyclosporin 1.25 mg kg(-1) daily (mean decrease 33.4%). Serum creatinine levels were significantly lower for groups with sirolimus alone and sirolimus plus reduced-dose cyclosporin when compared with cyclosporin 5.0 mg kg(-1) daily. Adverse events associated with sirolimus included thrombocytopenia (5%), hyperlipidaemia (9%), aphthous stomatitis (9%) and acne (13%), whereas adverse events associated with cyclosporin included hot flushes (12%), hyperlipidaemia (9%) and increased serum creatinine (9%). CONCLUSIONS: The concomitant administration of sirolimus with a subtherapeutic dose of cyclosporin in severe psoriasis may permit a reduction in their respective toxicities, notably cyclosporin-induced nephrotoxicity.     

Secukinumab efficacy and safety in Japanese patients with moderate‐to‐severe plaque psoriasis: Subanalysis from ERASURE,a randomized,placebo‐controlled,phase 3 study

Secukinumab, a fully human anti‐IL‐17A monoclonal antibody, neutralizes IL‐17A, a key cytokine in the pathogenesis of psoriasis. Efficacy and safety of secukinumab was evaluated in Japanese patients with moderate‐to‐severe plaque psoriasis as part of a large Phase 3 global study (ERASURE). In this 52‐week, double‐blind study (ClinicalTrials.gov Identifier: NCT01365455, JapicCTI‐111529), 87 patients from Japan (11.8% of 738 patients randomized in the overall study population) were equally randomized to receive secukinumab 300 mg or 150 mg, or placebo once weekly at baseline and at Weeks 1, 2, 3 and 4, then every 4 weeks. Co‐primary endpoints (Week 12) were ≥75% improvement in psoriasis area‐and‐severity index (PASI 75) from baseline and a score of 0 (clear) or 1 (almost clear) on a 5‐point Investigator's Global Assessment scale (IGA mod 2011 0/1) versus placebo. PASI 75 and IGA mod 2011 0/1 responses at Week 12 were superior with secukinumab 300 mg (82.8% and 55.2%, respectively) or 150 mg (86.2% and 55.2%, respectively) versus placebo (6.9% and 3.4%, respectively; P < 0.0001 for all). Greater than 90% improvement in PASI (PASI 90) was also superior with secukinumab 300 mg (62.1%) or 150 mg (55.2%) versus placebo (0.0%) at Week 12 (P < 0.0001 for both). Clinical responses were sustained up to Week 52 in the majority of patients. During a 12‐week induction period, adverse event incidences were 48.3% with secukinumab 300 mg, 55.2% with 150 mg, and 41.4% with placebo. Secukinumab showed robust and sustainable efficacy in symptom reduction for moderate‐to‐severe plaque psoriasis in the Japanese patients.     

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。     

A randomized controlled trial of narrowband ultraviolet B vs bath-psoralen plus ultraviolet A photochemotherapy for psoriasis

BACKGROUND: In 1991, consensus guidelines recommended psoralen plus ultraviolet A photochemotherapy (PUVA) for those requiring second-line therapy for psoriasis. Narrowband (TL-01) UVB has since become more widely available, replacing the less effective broadband sources. Objectives To compare the efficacy of TL-01 UVB phototherapy and trimethoxypsoralen (TMP) bath-PUVA for chronic plaque psoriasis. PARTICIPANTS AND METHODS: A randomized, observer-masked, intraindividually controlled, paired (half-body) study was done in the Photo(chemo)therapy Unit in Ninewells Hospital and Medical School, Dundee. The study comprised 28 patients (skin phototypes I-III) with chronic plaque psoriasis. Each patient's body halves (sagittal plane) were treated independently, one-half with TL-01 UVB, the other with bath-PUVA. Both treatments were administered according to standard, optimized regimens. Treatment was continued until clearance or minimal residual activity (MRA), or a maximum of 30 treatments. The main outcome measures were treatments and time to clearance/MRA, the proportion reaching clearance/MRA, change in psoriasis severity score (scaling, erythema and induration) and remission durations. RESULTS: Of 18 who completed the study, all reached clearance/MRA with TL-01, but three were still not clear after 30 PUVA exposures. TL-01 achieved clearance/MRA a median of 11 (6.5-25; P = 0.001) days more quickly than PUVA, but required a median of 24.5 compared with 19 exposures [95% confidence interval (CI) for difference 1.5-5.5; P = 0.01]. Ten patients were withdrawn (four because of inadequate response of PUVA-treated halves). Analysed on an intention-to-treat basis, 21 of 28 (75%) of all participants reached clearance/MRA with TL-01 compared with 15 of 28 (54%) with PUVA (95% CI for difference 4-37%; P = 0.03). Remission durations did not differ. CONCLUSIONS: When administered according to these regimens in a skin phototype I-III population, TL-01 UVB is more efficacious than TMP bath-PUVA in the treatment of chronic plaque psoriasis.     

Combining etanercept and acitretin in the therapy of chronic plaque psoriasis: a 24-week, randomized, controlled, investigator-blinded pilot trial

Background Combination treatments may increase efficacy while reducing dosages and side‐effects of individual agents. No randomized controlled trials have been published combining biologics with conventional agents for psoriasis. Objectives To investigate the efficacy and safety of the association of acitretin and etanercept in the treatment of moderate to severe chronic plaque psoriasis. Methods A 24‐week, randomized, controlled, investigator‐blinded pilot trial was conducted. Sixty adult patients with moderate to severe chronic plaque psoriasis were randomized into three groups to receive etanercept 25 mg twice weekly subcutaneously, oral acitretin 0·4 mg kg^?1 daily or etanercept 25 mg once weekly plus acitretin 0·4 mg kg^?1 daily. The primary end point was a 75% or greater improvement in Psoriasis Area and Severity Index (PASI) from baseline (PASI 75) at week 24. Results At week 24, PASI 75 response was achieved by 10 of 22 patients in the etanercept group (45%), six of 20 in the acitretin group (30%) and eight of 18 (44%) in the group treated with etanercept plus acitretin (P = 0·001 for both etanercept groups compared with acitretin alone). A 50% or greater improvement from baseline in PASI was achieved by 15 of 22 (68%), 10 of 20 (50%) and 12 of 18 (67%) patients, respectively (P = 0·001). The safety profiles of the three groups were similar. Conclusions A combined therapeutic regimen with etanercept 25 mg once weekly and acitretin 0·4 mg kg^?1 daily is as effective as etanercept 25 mg twice weekly, and more effective than acitretin alone. Although larger studies are needed to confirm these results, the etanercept/acitretin association could offer several advantages in the therapy of moderate to severe chronic plaque psoriasis.     

Efficacy and safety of calcipotriol plus betamethasone dipropionate scalp formulation compared with calcipotriol scalp solution in the treatment of scalp psoriasis: a randomized controlled trial

Background Current topical therapies for scalp psoriasis are difficult or unpleasant to apply, resulting in decreased adherence and efficacy. Objectives To compare the efficacy and safety of once‐daily treatment with a combination of calcipotriol 50 μg g^?1 plus betamethasone 0·5 mg g^?1 (as dipropionate) (Xamiol^®; LEO Pharma A/S, Ballerup, Denmark) and twice‐daily calcipotriol 50 μg mL^?1 scalp solution in patients with scalp psoriasis. Methods This 8‐week, multicentre, randomized, investigator‐blind, parallel‐group study compared two‐compound calcipotriol/betamethasone scalp formulation with calcipotriol scalp solution in patients with moderately severe scalp psoriasis. Primary efficacy outcome was the proportion of patients who achieved ‘clear’ or ‘minimal’ disease severity according to investigator’s global assessment of disease severity at week 8. Secondary efficacy outcomes and adverse events were also evaluated. Relapse and rebound were assessed in an 8‐week, post‐treatment observation phase. Results In total, 207 patients received the two‐compound scalp formulation and 105 patients received calcipotriol scalp solution. The proportion of patients with ‘clear’ or ‘minimal’ disease at week 8 was significantly greater in the two‐compound scalp formulation group (68·6%) than in the calcipotriol scalp solution group (31·4%; P < 0·001). Improvement was more rapid with the two‐compound scalp formulation than with calcipotriol scalp solution. Further evidence of the superiority of the two‐compound scalp formulation over the scalp solution was demonstrated through greater improvements in clinical signs and fewer adverse events. Conclusions A once‐daily combination of calcipotriol plus betamethasone dipropionate was significantly more effective and better tolerated than twice‐daily calcipotriol scalp solution in the treatment of scalp psoriasis.     

Combination of skin,joint and quality of life outcomes with etanercept in psoriasis and psoriatic arthritis in the PRESTA trial

Background Psoriasis and psoriatic arthritis (PsA) affect skin, and/or joints and quality of life (QoL). Objective To better assess the success in multiple attributes in subjects with both active psoriasis and PsA, the objective was to quantify the proportion of those who achieved substantial improvement in a composite measure of skin symptoms, joint manifestations, and QoL, on one of two treatment regimens. Methods Subjects (n = 752) with psoriasis and PsA (mean age: 46.5 years, 62.9% male) received etanercept (ETN) 50 mg twice weekly (BIW; n = 379) or 50 mg weekly (QW; n = 373) for 12 weeks, followed by open‐label ETN 50 mg QW for 12 weeks. Skin and joint symptoms and QoL were assessed using psoriasis area and severity index (PASI), American College of Rheumatology criteria (ACR) and Euro‐QoL (EQ‐5D), respectively. Results By week 24, 30.6% and 25.8% of subjects receiving ETN 50 mg BIW/QW and ETN 50 mg QW/QW, respectively (P = 0.198) achieved the composite measure of efficacy for skin plus joints plus QoL (PASI 75 + ACR 50 + EQ‐5D VAS >82). Conclusion At 24 weeks, 25.8–30.6% met the triad of rigorous efficacy outcomes. Evaluation of treatment efficacy should address the multiple components of this disease complex; therefore it may be important to consider this composite measure in future trials.     

Safety and efficacy of alefacept, efalizumab, etanercept and infliximab in treating moderate to severe plaque psoriasis: a meta-analysis of randomized controlled trials

Background The relatively recent introduction of biological agents to treat psoriasis presents clinicians with the need to objectively compare and contrast these agents to allow more effective treatment of their patients. Objectives To evaluate and compare the efficacy and safety of biological agents in the treatment of plaque psoriasis. Methods (i) Data sources: Four parallel systematic reviews conducted through July 2006, including peer‐reviewed data and U.S. Food and Drug Administration (FDA) reports. (ii) Study selection: Randomized, controlled, double‐blind, monotherapy trials of alefacept (n = 3), efalizumab (n = 5), etanercept (n = 4) and infliximab (n = 4); 16 studies comprising 7931 patients met inclusion criteria. (iii) Data extraction: Efficacy was measured by Psoriasis Area and Severity Index (PASI) 75 achievement after 10–14 weeks of treatment, using intention‐to‐treat analysis. Safety was evaluated by the incidence of one or more adverse event(s) (AEs) and serious adverse event(s) (SAEs) during 10–30 weeks of treatment. Results Pooled relative risk (RR) and number needed to treat (NNT) of PASI 75 achievement compared with placebo was computed using Mantel–Haenszel methods and the random effects model. All biological agents for psoriasis were efficacious (P < 0·001); however, there was a graded response for achievement of PASI 75: infliximab (RR = 17·40, NNT = 2), etanercept (RR = 11·73, NNT = 3), efalizumab (RR = 7·34, NNT = 4) and alefacept (RR = 3·70, NNT = 8). The risk of one or more AEs was evaluated by RR and number needed to harm (NNH). This was increased in the alefacept (RR = 1·09, P = 0·03, NNH = 15), efalizumab (RR = 1·15, P < 0·001, NNH = 9) and infliximab (RR = 1·18, P < 0·001, NNH = 9) groups compared with placebo. SAEs were increased in a sensitivity analysis of four efalizumab trials (n = 2443, RR = 1·92, P = 0·03, NNH = 60). Conclusions The decreasing rank order for pooled efficacy was infliximab, etanercept, efalizumab and alefacept when compared with placebo. Pooling safety data revealed a previously unreported increased risk of AEs for alefacept, efalizumab and infliximab.     

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.     

Optimization of photodynamic therapy with a novel self-adhesive 5-aminolaevulinic acid patch: results of two randomized controlled phase III studies

Background  Photodynamic therapy (PDT) is increasingly used for treatment of actinic keratoses (AKs) but is a cumbersome procedure. A thin self-adhesive patch (PD P 506 A) containing 5-aminolaevulinic acid (5-ALA) was developed to facilitate PDT.
Objectives  To investigate efficacy and safety of the patch in comparison with placebo–PDT (superiority design, observer-blinded; study AK 03) and standard therapy, cryosurgery (noninferiority design, open; study AK 04).
Methods  Two separate confirmatory randomized parallel-group phase III studies were set up. In total, 449 patients with up to eight mild to moderate AK study lesions located on the head were treated in 29 German study centres (study AK 03: 103 patients; study AK 04: 346 patients).
Results  Twelve weeks after treatment, 5-ALA patch–PDT proved to be superior to placebo–PDT ( P  < 0·001) and cryosurgery ( P  = 0·007). Efficacy rates on a lesion basis were 82% (AK 03) and 89% (AK 04) for PDT, 77% for cryosurgery and 19% (AK 03) and 29% (AK 04) for placebo–PDT. Local reactions at the treatment site occurred in almost all patients treated with 5-ALA patch–PDT or cryosurgery. Headache was the only side-effect not related to the treatment site which occurred in more than one patient.
Conclusions  PD P 506 A is an innovative, easy-to-handle 5-ALA patch for PDT of mild to moderate AK lesions. Compared with current PDT procedures, pretreatment (e.g. curettage) is not needed and handling is considerably facilitated. A single PDT treatment results in efficacy rates being statistically significantly superior to placebo and cryosurgery.     

Optimizing the frequency of outpatient short-contact dithranol treatment used in combination with broadband ultraviolet B for psoriasis: a randomized, within-patient controlled trial

BACKGROUND: Recent concerns over the side-effects of psoralen plus ultraviolet (UV) A, immunosuppressive and cytotoxic treatments have led to increased interest in dithranol for treatment of psoriasis. Few studies have investigated how frequently dithranol should be applied. Dithranol-induced inflammation is maximal at 48-72 h, suggesting that daily application of dithranol may not be optimal. OBJECTIVES: To investigate the effectiveness of five times weekly application of short-contact dithranol (SCD) compared with three times weekly application in a dedicated hospital outpatient treatment unit. METHODS: A randomized, within-patient, controlled study was performed. Patients had SCD applied five times weekly to one half of the body, and three times weekly to the other side. Whole-body UVB irradiation was given 5 days a week. Patients were assessed weekly for 8 weeks. Principal outcome measures were percentage reduction in modified Psoriasis Area and Severity Index (mPASI) at the end of study and time to 50% improvement in mPASI score. RESULTS: Twenty-nine patients were recruited; four were excluded from analysis. Mean percentage reduction in mPASI score at the end of study for five times weekly application was 57.3% (95% confidence interval, CI 39.6-75.0%) and for three times weekly application was 55.4% (95% CI 37.8-73.1%; P = 0.34). Mean time to 50% improvement in mPASI for five times weekly treatment was 4.1 weeks and for three times weekly treatment was 4.0 weeks (P = 0.50). There was no difference in the frequency or severity of burning episodes for each side. CONCLUSIONS: This study suggests that three times weekly application of SCD may be as effective as five times weekly when used in conjunction with UVB administered five times weekly. Large studies of whole-body comparisons are warranted to assess further the optimal frequency of SCD and UVB therapy for psoriasis.     

Efficacy of betamethasone valerate mousse in comparison with standard therapies on scalp psoriasis: an open,multicentre, randomized,controlled, cross-over study on 241 patients

BACKGROUND: The scalp is a common area for plaque psoriasis. Corticosteroid-based lotions are the most widely used therapy in this clinical setting. A new formulation of betamethasone valerate 0.12% in a thermophobic, low-residue foam vehicle (Bettamousse trade mark, Mipharm, Italy; BVM) is available for the treatment of scalp dermatoses. OBJECTIVES: In an open, investigator-blinded, multicentre (28 dermatology clinics), randomized, cross-over study, the efficacy, safety and patient acceptability of BVM in scalp psoriasis were evaluated in comparison with standard therapies (ST, i.e. corticosteroids or vitamin D analogues). ST were chosen by each centre according to its usual therapeutic protocols. METHODS: In total, 241 patients with moderate to severe scalp psoriasis participated in the trial. After a 2-week run-in period, each active treatment (BVM or ST) was applied for 4 weeks, with a wash-out period between the two active treatment phases of at least 4 weeks. Efficacy was evaluated by investigators unaware of treatment sequence analysing a 'target' lesion for erythema, scaling, itching and burning using a five-point grading score. Patient treatment acceptability and assessment of the influence on Psoriasis Disability Index were evaluated using an eight-item modified Finlay-Khan questionnaire at baseline and at the end of each treatment period. Safety was evaluated by recording any adverse event occurring during the study duration. BVM was applied twice daily, and ST were applied once or twice daily, according to the approved scheduled regimens. RESULTS: Analyses were by intention-to-treat. Two hundred and ten patients concluded the study. Fifteen patients withdrew from the study during BVM treatment, and 16 during ST (not significantly different). Both treatments were well tolerated. At baseline, the mean +/- SD clinical global score (the 'Sum' score = erythema + scaling + itching + burning) was 7.6 +/- 2.6. The ST chosen were topical corticosteroids (55% of cases; mainly mometasone and betamethasone dipropionate) or calcipotriol lotion (45% of cases). At the end of active treatments, BVM was significantly superior to ST (P < 0.001) in reducing, as compared with baseline, the mean +/- SD Sum score (1.5 +/- 1.9 with BVM and 3.1 +/- 2.7 with ST). During BVM treatment, 88% (95% confidence interval, CI 82-94%) of patients had a complete or nearly complete resolution of scaling in comparison with 66% (95% CI 58-74%) during ST therapy (P < 0.001). BVM was also considered an easier and more convenient formulation to use in comparison with ST (P < 0.01). CONCLUSIONS: BVM is more effective than lotion-based ST commonly used in the treatment of scalp psoriasis, and has higher patient acceptability.     

Narrowband ultraviolet B therapy in psoriasis: randomized double‐blind comparison of high‐dose and low‐dose irradiation regimens

Background Ultraviolet (UV) B phototherapy is an established treatment option for psoriasis. The optimum dosage regimen still has to be determined. Within‐subject comparisons do not take into account the systemic effects of UVB phototherapy. The area of the body treated with low‐dose UVB may benefit from the systemic effects of the site treated with a higher UVB dose. Objectives To study the time to clearance in patients with psoriasis in a randomized controlled trial, in which patients were treated with narrowband UVB in either a high‐dose or a low‐dose regimen. Methods One hundred and nine patients were randomized to a high‐dose regimen (group 1) or to a low‐dose regimen (group 2). Patients of group 1 and 2 were irradiated with 40% and with 20% incremental doses, respectively, three times weekly. Psoriasis Area and Severity Index (PASI) was measured at baseline and at every 4‐week control visit. Treatment was stopped in cases of clearance (90% reduction of baseline PASI). Results No significant differences were found in the number of patients achieving clearance. The high‐dosage scheme resulted in four fewer treatments with no significant differences in cumulative UV dose, although more protocol adjustments were required in the beginning of the study because of erythema. After 3 months a significantly better clinical outcome was seen after high‐dose UVB therapy. Conclusions High‐dose UVB therapy results in fewer treatments with better long‐term efficacy, with cost‐effective benefits for hospital and patients. Therefore UVB phototherapy in a high‐dose regimen for psoriasis is recommended. However, a protocol adjustment in the second week with a high‐dose regimen is desirable to prevent erythema.