Brodalumab, an anti-interleukin-17-receptor antibody for psoriasis.

BACKGROUND: In this phase 2, randomized, double-blind, placebo-controlled, dose-ranging study, we assessed the efficacy and safety of brodalumab (AMG 827), a human anti-interleukin-17-receptor monoclonal antibody, for the treatment of moderate-to-severe plaque psoriasis. METHODS: We randomly assigned patients with a score of 12 or higher on the psoriasis area-and-severity index (PASI, on which scores range from 0 to 72, with higher scores indicating more severe disease) and with 10% or more of their body-surface area affected by psoriasis to receive brodalumab (70 mg, 140 mg, or 210 mg at day 1 and weeks 1, 2, 4, 6, 8, and 10 or 280 mg monthly) or placebo. The primary end point was the percentage improvement from baseline in the PASI score at week 12. Secondary end points included improvement of at least 75% and at least 90% in the PASI score and the score on the static physician's global assessment at week 12. RESULTS: A total of 198 patients underwent randomization. At week 12, the mean percentage improvements in the PASI score were 45.0% among patients receiving 70 mg of brodalumab, 85.9% among those receiving 140 mg, 86.3% among those receiving 210 mg, 76.0% among those receiving 280 mg, and 16.0% among those receiving placebo (P<0.001 for all comparisons with placebo). An improvement of at least 75% and at least 90% in the PASI score at week 12 was seen in 77% and 72%, respectively, of the patients in the 140-mg brodalumab group and in 82% and 75%, respectively, of the patients in the 210-mg group, as compared with 0% in the placebo group (P<0.001 for all comparisons). The percentage of patients with a static physician's global assessment of clear or minimal disease was 26%, 85%, 80%, and 69% with the 70-mg, 140-mg, 210-mg, and 280-mg doses, respectively, of brodalumab, as compared with 3% with placebo (P<0.01 for all comparisons with placebo). Two cases of grade 3 neutropenia were reported in the 210-mg brodalumab group. The most commonly reported adverse events in the combined brodalumab groups were nasopharyngitis (8%), upper respiratory tract infection (8%), and injection-site erythema (6%). CONCLUSIONS: Brodalumab significantly improved plaque psoriasis in this 12-week, phase 2 study. (Funded by Amgen; ClinicalTrials.gov number, NCT00975637.).

Prevalence of undiagnosed psoriatic arthritis among psoriasis patients: Systematic review and meta-analysis.

BACKGROUND: Skin psoriasis precedes the onset of psoriatic arthritis (PsA) in 84% of patients with psoriasis. Dermatologists have an important role to screen psoriasis patients for PsA. The efficiency of PsA screening remains unknown. OBJECTIVE: We sought to determine the point prevalence of undiagnosed PsA in patients with psoriasis using a systematic search of the literature and meta-analysis. METHODS: PubMed, Cochrane, and Embase database searches yielded 394 studies for review. No study aimed to determine the prevalence of undiagnosed PsA in patients with psoriasis. We assumed that the prevalence of newly diagnosed PsA in patients with psoriasis at the time they seek medical care could be a sound estimate of this value. Seven epidemiological studies and 5 studies on PsA screening questionnaires allowed us to clearly identify patients with newly diagnosed PsA and were selected for review. RESULTS: The prevalence of undiagnosed PsA was 15.5% when all studies were considered and 10.1% when only epidemiological studies were considered. LIMITATIONS: Data were obtained from studies not designed to address the question at hand. Heterogeneity was high (I(2) = 96.86%), and therefore a random effects model was used. CONCLUSION: The high prevalence of undiagnosed PsA in patients with psoriasis adds to the recommendation that dermatologists need to screen all patients with psoriasis for PsA.

A 52-week trial comparing briakinumab with methotrexate in patients with psoriasis.

BACKGROUND: Briakinumab is a monoclonal antibody against the p40 molecule shared by interleukin-12 and interleukin-23, which is overexpressed in psoriatic skin lesions. We assessed the efficacy and safety of briakinumab as compared with methotrexate in patients with psoriasis. METHODS: In this 52-week trial, we randomly assigned 317 patients with moderate-to-severe psoriasis to briakinumab, at a dose of 200 mg at weeks 0 and 4 and 100 mg at week 8 and every 4 weeks thereafter (154 patients), or methotrexate, at a dose of 5 to 25 mg weekly (163 patients). The primary end points were the percentages of patients with at least 75% improvement in the score on the psoriasis area-and-severity index (PASI) at weeks 24 and 52 and a score on the physician's global assessment of 0 (clear; i.e., no apparent disease) or 1 (minimal disease) at weeks 24 and 52. A total of 248 patients were enrolled in an ongoing 160-week open-label continuation study. RESULTS: At week 24, a total of 81.8% of the patients in the briakinumab group versus 39.9% in the methotrexate group had at least 75% improvement in the PASI score, and 80.5% versus 34.4% had a score of 0 or 1 on the physician's global assessment. The corresponding percentages at week 52 were 66.2% versus 23.9% with at least a 75% improvement in the PASI score and 63.0% versus 20.2% with a score of 0 or 1 on the physician's global assessment (P<0.001 for all comparisons). During the 52-week study, serious adverse events occurred in 9.1% of the patients in the briakinumab group (12.9 events per 100 patient-years) and in 6.1% in the methotrexate group (10.6 events per 100 patient-years). Serious infections occurred in 2.6% of the patients in the briakinumab group (4.1 events per 100 patient-years) and in 1.8% in the methotrexate group (2.7 events per 100 patient-years); cancers occurred in 1.9% (2.0 events per 100 patient-years) versus 0%. CONCLUSIONS: Briakinumab showed higher efficacy than methotrexate in patients with moderate-to-severe psoriasis. Serious infections and cancers occurred more frequently with briakinumab, but the differences were not significant. (Funded by Abbott Laboratories; ClinicalTrials.gov number, NCT00679731.).

Diagnosis and treatment monitoring of toenail onychomycosis by reflectance confocal microscopy: prospective cohort study in 58 patients.

BACKGROUND: The clinical presentation of onychomycosis is often nonspecific and can lead to inappropriate antifungal therapy. Available mycologic tests share many drawbacks. OBJECTIVE: We sought to evaluate the accuracy of reflectance confocal microscopy (RCM) for the diagnosis of onychomycosis compared with standard mycologic tests. METHODS: In all, 58 patients with suspected onychomycosis were enrolled prospectively. RCM, potassium hydroxide preparation, and fungal culture were performed at baseline and after treatment in patients with confirmed onychomycosis. RCM diagnosis of onychomycosis was based on the presence of filamentous and/or roundish structures in the nail plate, corresponding respectively to septate hyphae and/or arthroconidia. RESULTS: Of patients, 46 of 58 were correctly classified by RCM, with a diagnosis yield of 79.3%, sensitivity of 52.9%, specificity of 90.2%, positive predictive value of 69.2%, and negative predictive value of 82.2%. The use of a handheld RCM imager permitted a faster examination with the same accuracy. RCM performed after treatment in 9 patients showed a normal nail plate, and healing was confirmed by mycologic tests or by follow-up. LIMITATIONS: Existing RCM scanner heads are not intended for nail examination. CONCLUSION: RCM has excellent specificity and can be used as a rapid, office-based test to strengthen the prescription of antifungal therapy and for follow-up. Technical improvement could aid sensitivity.

The caspase-cleaved form of LYN mediates a psoriasis-like inflammatory syndrome in mice.

We showed previously that Lyn is a substrate for caspases, a family of cysteine proteases, involved in the regulation of apoptosis and inflammation. Here, we report that expression of the caspase-cleaved form of Lyn (LynDeltaN), in mice, mediates a chronic inflammatory syndrome resembling human psoriasis. Genetic ablation of TNF receptor 1 in a LynDeltaN background rescues a normal phenotype, indicating that LynDeltaN mice phenotype is TNF-alpha-dependent. The predominant role of T cells in the disease occurring in LynDeltaN mice was highlighted by the distinct improvement of LynDeltaN mice phenotype in a Rag1-deficient background. Using pan-genomic profiling, we also established that LynDeltaN mice show an increased expression of STAT-3 and inhibitory members of the NFkappaB pathway. Accordingly, LynDeltaN alters NFkappaB activity underlying a link between inhibition of NFkappaB and LynDeltaN mice phenotype. Finally, analysis of Lyn expression in human skin biopsies of psoriatic patients led to the detection of Lyn cleavage product whose expression correlates with the activation of caspase 1. Our data identify a new role for Lyn as a regulator of psoriasis through its cleavage by caspases.

Cystinosin is a melanosomal protein that regulates melanin synthesis.

Cystinosis is a rare autosomal recessive disease characterized by cystine crystal accumulation leading to multiorgan dysfunctions and caused by mutation in CTNS. CTNS encodes cystinosin, a cystine/H(+) symporter that exports cystine out of the lysosomes. Patients with cystinosis frequently exhibit blond hair and fair complexion, suggesting an alteration in melanogenesis. However, the pigmentation singularities of these patients have not been studied, and the role of cystinosin in melanogenesis has remained unknown. In our study, a clinical evaluation of 27 patients with cystinosis showed that 44% had a cutaneous pigmentation dilution compared to their relatives. Analysis of the hair melanin content in these patients by HPLC demonstrated a 50% decrease in eumelanin (4360 vs. 9360 ng/mg), and a 2-fold increase in pheomelanin (53 vs. 20 ng/mg), the yellow/red pigments. Cystinosin-deficient mice also showed a 4-fold increase in hair pheomelanin content. In vitro studies showed that cystinosin was located at melanosomes. CTNS silencing led to a 75% reduction of melanin synthesis that was caused by a degradation of tyrosinase by lysosomal proteases. Our results objectify the pigmentation defect in patients with cystinosis. We also identify the role of CTNS in melanogenesis and add a new gene to the list of the genes involved in the control of skin and hair pigmentation.

In vivo reflectance confocal microscopy of the skin: a noninvasive means of assessing body cystine accumulation in infantile cystinosis.

BACKGROUND: Patients with infantile nephropathic cystinosis have progressive accumulation of cystine in tissues leading to delayed extrarenal complications. No simple tool is available to evaluate the level of body cystine accumulation. OBJECTIVE: We sought to determine the value of in vivo reflectance confocal microscopy of the skin in patients with infantile nephrogenic cystinosis. METHODS: Nine patients and control subjects were recruited for this study. Images were acquired by means of a near-infrared reflectance confocal laser scanning microscope. RESULTS: Scattered bright particles within the papillary dermis were observed in all patients but not in control subjects. The density of particles ranged from numerous (+++) to very few (+/-) and their distribution was heterogeneous. Electron microscopy confirmed that these particles corresponded to cystine crystal deposits within dermal fibroblasts. The density of cystine crystals within the dermis was greater in older patients, in patients with a high leukocyte cystine concentration, and with delayed cysteamine therapy. There was no correlation between the density of cystine deposits and renal disease or hypopigmentation but high levels of deposition occurred in association with extrarenal manifestations. LIMITATIONS: This is a preliminary study on a small sample of patients. Repeated examination and longer follow-up is necessary. CONCLUSION: In vivo reflectance confocal microscopy of the skin appears to be a noninvasive means of assessing body cystine accumulation in infantile cystinosis and could be used as a complementary marker of treatment response in addition to leukocyte cystine measurement.

Signalling and chemosensitivity assays in melanoma: is mutated status a prerequisite for targeted therapy?

Selection for targeted therapies in melanoma is currently based on the search for mutations in selected genes. We aimed at evaluating the interest of signalling and chemosensitivity studies in addition to genotyping for assessing the best suitable treatment in an individual patient. We extracted genomic DNA and melanoma cells from tumor tissue of a skin metastasis of a 17-year-old woman with stage IV melanoma progressing despite three successive lines of treatment. Despite the absence of mutation in BRAF, NRAS cKIT, the MAPK pathway was activated and a significant response to sorafenib, a mitogen-activated protein kinase (MAPK)/RAF inhibitor, was found in signalling and chemosensitivity assays. A treatment combining sorafenib and dacarbazine produced a partial response for 9 months, with marked necrosis in some lesions. Chemosensitivity assays and signalling pathway studies could be of great value in addition to genotyping for assessing the most appropriate treatment in melanoma.

Reliability assessment and validation of the Melasma Area and Severity Index (MASI) and a new modified MASI scoring method.

BACKGROUND: The Melasma Area and Severity Index (MASI), the most commonly used outcome measure for melasma, has not been validated. OBJECTIVE: We sought to determine the reliability and validity of the MASI. METHODS: After standardized training, 6 raters independently rated 21 patients with mild to severe melasma once daily over a period of 2 days to determine intrarater and interrater reliability. Validation was performed by comparing the MASI with the melasma severity scale. The darkness component of the MASI was validated by comparing it with the difference between mexameter scores for affected versus adjacent normal-appearing skin. The area component of the MASI was validated by comparing it with the area of each section of the face determined by computer-based measurement software. RESULTS: The MASI score showed good reliability within and between raters and was found to be valid when compared with the melasma severity scale, mexameter scores, and area measurements. Homogeneity assessment by raters showed the least agreement and can be removed from the MASI score without any loss of reliability. LIMITATIONS: Patients were limited to Hispanic, African, and Asian backgrounds. CONCLUSION: The MASI is a reliable measure of melasma severity. Area of involvement and darkness are sufficient for accurate measurement of the severity of melasma and homogeneity can be eliminated.

Clinical and cytological effects of pimecrolimus cream 1% after resolution of active atopic dermatitis lesions by topical corticosteroids: a randomized controlled trial.

BACKGROUND: Topical pimecrolimus may maintain remissions of atopic dermatitis (AD) by inhibiting subclinical inflammation. OBJECTIVE: To evaluate clinical and cytological effects of pimecrolimus in topical corticosteroid-treated and resolved AD lesions. METHODS: Patients (n=67) with resolved AD lesions were randomized to 3-week double-blind treatment with either pimecrolimus cream 1% or vehicle cream. Outcome measures were reduction in Eczema Area and Severity Index (EASI) and number of leukocytes in skin biopsies in all randomized patients who were evaluable at the end of study. RESULTS: The proportion of patients with a localized EASI<2 at the end of study was higher with pimecrolimus cream 1% than with vehicle cream (73.5 vs. 39.4%, respectively). There was a significant decrease in the number of infiltrating CD45+ cells in pimecrolimus cream 1% compared with placebo cream (-88.2 vs. 43.2 cells/mm(2), respectively, p=0.047) and a slight but nonsignificant reduction in the number of dermal dendritic cells, Langerhans cells, T cells and macrophages with pimecrolimus versus vehicle cream. LIMITATIONS: This was an exploratory study. CONCLUSION: Topical pimecrolimus was effective at maintaining betamethasone-17α-valerate-induced AD remission by inhibiting recurrences of the inflammatory infiltrate in the skin.

A pilot study using reflectance confocal microscopy (RCM) in the assessment of a novel formulation for the treatment of melasma.

INTRODUCTION: Melasma is a common pigmentary disorder caused by abnormal melanin deposits within the skin. Hydroquinone (HQ) is presently the most popular depigmenting agent, however the treatment of melasma remains unsatisfactory, resulting in a need to evaluate new depigmenting agents. OBJECTIVE: The objective of this study was to assess, using standard methods and a novel technique, in vivo Reflectance Confocal Microscopy (RCM), the efficacy and safety of a new non-HQ bleaching agent Dermamelan® (Mesoestetic, Barcelona, Spain) in the treatment of melasma. METHODS: Ten women with melasma were enrolled in an open-label trial lasting four months. Patients were of Fitzpatrick skin types II-IV. A non-HQ depigmenting agent (Dermamelan) was applied once-daily for three months. Melasma Area and Severity Indices (MASI) were measured. Standard and UV-light photographs were taken and in vivo RCM, which detects pigmentary changes at a cellular level, was done. Evaluations were performed before treatment, on the first, second and third month of treatment and one month after treatment. Upon cessation of the trial, patients completed a questionnaire regarding efficacy and tolerance. RESULTS: At baseline, RCM detected hyperpigmented keratinocytes in all patients, dendritic cells in 2/10 patients, and melanophages in 2/10 patients. Based on the MASI score, Dermamelan treatment improved melasma by 50 percent. This was confirmed by standard and UV-light photography. Maximum therapeutic effect was usually reached by one month of treatment and was maintained at one month following its completion. Interestingly Dermamelan treatment also induced a statistically significant decrease of pigmented epidermal keratinocytes as detected by RCM. Patients with melanophages on RCM at baseline had a poorer outcome, but not those with dendritic cells. Mild irritation was the only adverse event observed during treatment. The majority of patients were satisfied with the result. CONCLUSION: This study suggests that Dermamelan produces significant rapid improvement of melasma at a clinical and cellular level and demonstrates the potential of RCM to monitor and possibly predict efficacy of a new depigmenting agent in the treatment of melasma.

Reflectance confocal microscopy for pigmentary disorders.

In vivo reflectance confocal microscopy (RCM) is a non-invasive, repetitive imaging tool that provides real-time images at nearly cellular histological resolution. Application of this technology to skin imaging during the last decade has been a great advance in dermatology. As melanin is the strongest endogenous contrast in human skin, pigmentary disorders caused by abnormal amounts of melanin in the skin could be the most suitable candidates for RCM examination. This article reviewed the RCM applications in the characterization and management of pigmentary disorders. The application of RCM in pigmentary disorders has been expanded to describe hyper- and hypopigmentary disorders as well as pigmented skin tumors. The great advantages of non-invasive and repetitive examination of RCM may provide its usefulness not only in the diagnosis and management of pigmentary disorders, but also in researching pathogenesis of pigmentary disorders.

Effectiveness of cross polarized light and fluorescence diagnosis for detection of sub-clinical and clinical actinic keratosis during imiquimod treatment.

BACKGROUND: During treatment of actinic keratosis (AK) lesions with imiquimod sub-clinical lesions often become visible. It is, however, unclear whether these sub-clinical lesions would be detectable beforehand. OBJECTIVE: The aim of this pilot study was to compare two techniques, cross polarized light photography (CPL) and fluorescence diagnosis (FD) using methyllevulinic acid and illumination with Wood's lamp for their ability to detect sub-clinical lesions. These findings were also compared with biopsy results taken before and after treatment with imiquimod 5% cream or vehicle. METHODOLOGY: Twelve patients with at least five clinically visible AK lesions in a single contiguous 20 cm(2) area on the head were recruited. Patient eligibility was determined at the screening visit, when they were randomized to treatment. The randomization was 3:1, active to vehicle (nine treated with imiquimod, three with vehicle cream) for a total duration of 24 weeks (six clinic visits). Patients were assessed for baseline AK lesion counts (clinical and sub-clinical) at the screening visit and final counts at week 20. RESULTS: The number of clinically observed AK lesions was significantly lower at week 12 and week 20 compared with baseline following imiquimod treatment versus vehicle. The number of counted lesions were significantly higher using the CPL method compared with clinical counting with imiquimod treatment at baseline (8.3 +/- 3.4 vs 5.8 +/- 1.3; P = 0.027) and week 20 (4.8 +/- 2.4 vs 3.0 +/- 1.7; P = 0.02) but not in the vehicle group. The FD lesion counting method did not show a significant increase in the number of detected lesions compared with clinical analysis in the imiquimod and placebo groups but when comparisons were performed using pooled data (treatments and visits combined) the results were significant. CONCLUSION: The number of sub-clinical and clinical AK lesions detected during treatment with imiquimod can be better demonstrated using the methods of CPL and FD, but statistical significance was reached only using the CPL method. This is only a preliminary study with a small number of patients and as a result it is difficult to conclude both statistical and clinical significance. However, results were encouraging and indicate that larger studies are needed to demonstrate the relevance of these two new methods for improved detection of clinical and especially sub-clinical AK lesions.

In vivo reflectance confocal microscopy detects pigmentary changes in melasma at a cellular level resolution.

Melasma is a frequent pigmentary disorder caused by abnormal melanin deposits in the skin. In vivo reflectance confocal microscopy (RCM) is a repetitive imaging tool that provides real-time images of the skin at nearly histological resolution. As melanin is the strongest endogenous contrast in human skin, pigmentary disorders are the most suitable candidates for RCM examination but RCM features of melasma have never been reported. This study investigates the pilot use of RCM in melasma to provide a set of well-described morphological criteria with histological correlations. RCM images were acquired from melasma skin and compared to adjacent control skin in 26 patients. Skin biopsies were obtained from eight patients. In the epidermis, RCM showed in all patients a significant increase in hyperrefractile cobblestoning cells. These cells corresponded to hyperpigmented basal keratinocytes in histology. In six patients, dendritic cells corresponding to activated melanocytes were also found in the epidermis. In the dermis, RCM identified in nine patients plump bright cells corresponding to melanophages. Interestingly, for a given patient, the topographic distribution of melanophages in melasma lesions was very heterogeneous. RCM also showed a significant increase in solar elastosis and blood vessels in the dermis. RCM is a non-invasive technique that detects pigmentary changes in melasma at a cellular level resolution. Therefore, RCM provides an innovative way to classify melasma by pigment changes.

The safety profile and sustained remission associated with response to multiple courses of intramuscular alefacept for treatment of chronic plaque psoriasis.

BACKGROUND: Safety and efficacy of up to 3 courses of alefacept intramuscular (IM) in the treatment of chronic plaque psoriasis have been demonstrated in earlier trials. OBJECTIVE: We sought to determine the safety and efficacy of up to 5 courses of alefacept IM in treating plaque psoriasis. METHODS: A standard treatment course was defined as 15 mg of alefacept IM once weekly for 12 weeks, followed by 12 weeks of treatment-free observation. Patients with chronic plaque psoriasis, who had previously received alefacept IM, received up to 3 additional courses (A, B, and C). Efficacy was evaluated by Physician Global Assessment. RESULTS: Safety profiles were similar to those for a single course of treatment. There were no cumulative adverse effects. At 2 weeks postdosing, 16%, 22%, and 19% of patients were rated clear or almost clear by Physician Global Assessment in courses A, B, and C, respectively, with 35%, 42%, and 42% achieving this response at any time during these courses. Patients who achieved clear or almost clear at 2 weeks postdosing remained so for a median duration of 214 and 126 days after courses A and B, respectively. LIMITATIONS: This was an extension study and therefore contained no control group. CONCLUSIONS: Up to 5 courses of alefacept IM may provide extended treatment-free, symptom-free periods in responders while maintaining the safety profile.

Ustekinumab significantly improves symptoms of anxiety, depression, and skin-related quality of life in patients with moderate-to-severe psoriasis: Results from a randomized, double-blind, placebo-controlled phase III trial.

BACKGROUND: Anxiety, depression, and impaired health-related quality of life (HRQoL) are common in patients with psoriasis. OBJECTIVE: We sought to analyze the effect of ustekinumab on these conditions in patients with moderate-to-severe psoriasis. METHODS: Patients with moderate-to-severe psoriasis (n = 1230) were randomized 1:1:1 to receive 45 mg of ustekinumab, 90 mg of ustekinumab, or placebo. The Hospital Anxiety and Depression Scale was used to measure anxiety and depression, and the Dermatology Life Quality Index to measure HRQoL. RESULTS: At baseline, 40.3% and 26.7% of patients reported symptoms of anxiety and depression, respectively, and 54.6% reported Dermatology Life Quality Index scores greater than 10, indicating a very high impact of disease on HRQoL. Greater improvements at week 12 in mean Hospital Anxiety and Depression Scale-Anxiety (13.9%), Hospital Anxiety and Depression Scale-Depression (29.3%), and Dermatology Life Quality Index (76.2%) scores were reported in ustekinumab groups compared with placebo (P < .001 each). LIMITATIONS: Results for these measures are reported only through 24 weeks. CONCLUSION: Patients receiving ustekinumab reported significant improvements in symptoms of anxiety, depression, and HRQoL.

Skin and nail responses after 1 year of infliximab therapy in patients with moderate-to-severe psoriasis: a retrospective analysis of the EXPRESS Trial.

BACKGROUND: The EXPRESS study demonstrated the initial efficacy of infliximab in psoriasis affecting the skin and nails. OBJECTIVE: To further assess how patients with a positive initial response to infliximab respond to 1 year of continuous infliximab treatment. METHODS: A retrospective analysis of patients with moderate-to-severe plaque and nail psoriasis who initiated and continued infliximab treatment up to week 46 was conducted. RESULTS: Among all nail psoriasis patients receiving 1 year of infliximab (n = 186), 74.6 and 54.1% achieved at least 75 or 90% improvement in the Psoriasis Area and Severity Index (PASI) at week 50. These PASI-75 (n = 138) and PASI-90 (n = 100) responders had respective mean improvements from baseline to week 50 of 93.6 and 97.3% for the PASI, 90.6 and 94.1% for the Dermatology Life Quality Index (DLQI) and 78.2 and 80.3% for the Nail Psoriasis Severity Index (NAPSI). CONCLUSIONS: Infliximab treatment for 1 year produced sustained improvement in PASI, DLQI and NAPSI scores.

Comparison of two different dose combinations of calcipotriol/hydrocortisone ointment used once daily for the treatment of psoriasis vulgaris on the face and body.

A calcipotriol/hydrocortisone combination ointment has been developed for treating psoriasis on sensitive skin areas such as the face. The efficacy and safety of two calcipotriol/hydrocortisone dose combinations were compared with two concentrations of calcipotriol in the same ointment vehicle in patients with psoriasis on the face and body. Patients were randomised to receive 8 weeks once daily treatment with calcipotriol 25 mcg/g or 50 mcg/g, either alone or combined with hydrocortisone 10 mg/g. On the body and face overall, no statistically significant differences in efficacy were observed between the calcipotriol/hydrocortisone formulations versus the calcipotriol alone formulations nor between the two concentrations of calcipotriol (50 mcg/g versus 25 mcg/g). On the face alone, calcipotriol/hydrocortisone was significantly more effective than calcipotriol alone (P < 0.001) but no consistent significant difference was found between the two concentrations of calcipotriol. There was a significant benefit of combining hydrocortisone with calcipotriol in the incidence of adverse drug reactions on the body and face (P = 0.006) and on the face (P < 0.001) but no significant difference was found between the two concentrations of calcipotriol either on the body and face or on the face. In facial psoriasis, combining hydrocortisone with calcipotriol resulted in an improved efficacy and tolerability compared to calcipotriol alone.

Long-term safety and efficacy of etanercept in patients with psoriasis: an open-label study.

BACKGROUND: In two previous phase 3 studies, up to 60 weeks of etanercept therapy significantly improved the symptoms of psoriasis and was well tolerated. OBJECTIVE: To evaluate the long-term safety of etanercept in an open-label extension study for up to 72 weeks in patients with moderate-to-severe plaque psoriasis. METHODS: A total of 912 patients received 50 mg subcutaneous etanercept once weekly (OW) for the first 12 weeks of this extension study. Thereafter, eligible patients could maintain the 50 mg QW dose (n = 321) or escalate to 50 mg twice weekly (BIW; n = 591) anytime thereafter based on one of three predetermined criteria. RESULTS: Etanercept was well tolerated during 1056 patient-years of exposure; no difference was observed between the 50 mg QW and 50 mg BIW dosages in rates of adverse events and infections. Improvement in skin disease was maintained throughout the study. Patients who stopped and then restarted etanercept also showed improvement in psoriasis. CONCLUSION: Psoriatic patients continued to benefit from open-label etanercept treatment, both continuous and interrupted therapy, which was generally well tolerated after a combined 2.5 years of experience.

Juvenile psoriasis and its clinical management: a European expert group consensus.

BACKGROUND: Psoriasis, an inflammatory disorder of the skin, can significantly impact on a patient's quality of life, affecting their daily activities and families. The onset of psoriasis in childhood is quite common; however, the treatment of moderate-to-severe disease in this population is challenging, with a paucity of data reported and few licensed agents available. METHODS: A Delphi survey was conducted among a panel of European expert dermatologists and physicians with a particular interest in pediatric inflammatory disorders. The survey covered the aspects of psoriasis types, psoriatic arthritis, diagnosis and treatment options in childhood. RESULTS: A series of consensus opinions were reached, detailing the current practice in Europe for the diagnosis and treatment of psoriasis in childhood. These opinions are presented in the context of evidence from the literature and the current licensure status and indications of therapies for psoriasis in childhood. CONCLUSIONS: These data provide detailed information on the current practices in Europe for treating psoriasis in childhood.