Moderate Plaque Psoriasis Research Articles

Biologic Therapy in Psoriasis: Safety Profile.

This review focuses on the emerging concepts concerning the efficacy profile of biological drugs in psoriasis ranging from moderate to severe, and attempts to provide the most recent individual positioning of biologics in treating psoriasis. Biologic agents targeting towards specific immune mediators have emerged as treatment options for patients with moderate to-severe plaque psoriasis unresponsive or intolerant to traditional systemic agents. Data on the safety of biologics are available for up to 5 years in psoriasis and are on the whole reassuring. National registries are still evolving and will provide data on safety, to help the long-term monitoring of patients with psoriasis ongoing biological treatment. Although several biologics have demonstrated good efficacy and tolerability in short-term trials, treatment guidelines recommend them as third line therapies due to relative lack of long-term safety data, especially for those who have been commercialized recently. Here, we have reviewed the long-term safety data obtained from National Registries, randomized controlled trials, open-label extension studies and meta-analyses on etanercept, infliximab, adalimumab, and ustekinumab in the treatment of adults with moderate to severe plaque psoriasis.

Should self-destructive behavior affect a patient's access to scarce medical resources?

A 35-year-old man with moderate plaque psoriasis and psoriatic arthritis that has been well controlled on methotrexate (MTX) 20 mg weekly for the last 4 months presents for follow-up. He recently heard about adalimumab, and asks about starting treatment with this drug. He explains that although he has abstained from drinking while taking MTX, he craves alcohol. He had previously been on acitretin for years, during which time he was usually abstinent, but during the transition from acitretin to MTX, he was frequently intoxicated. Today, his skin is clear. He has not had any side effects while on MTX, but he states, ‘‘I want to live the way I want to,’’ including engaging in binge drinking. What is the clinician’s best course of action? A. Agree to switch the patient to adalimumab because he wishes to freely drink alcohol and have less laboratory monitoring. B. Continue MTX because it has controlled his disease and has not caused any adverse effects. C. Advise the patient that he can safely drink less than 100 g of alcohol per week while taking MTX, but will still need laboratory monitoring. D. Tell the patient that you cannot continue treating him unless he enrolls in an alcohol treatment program.

Topical Turmeric Microemulgel in the Management of Plaque Psoriasis; A Clinical Evaluation.

Psoriasis is an autoimmune and recurrent chronic inflammatory skin disease. About 1-3% of the world wide populations are affected. The characteristic features are hyperprolifration of keratinocytes leading to redness, thickening and scaling of epidermis followed with itching and appearance of the lesions which in most cases bother the patients medically and psychologically. Psoriasis is symptomatically treated by the range of oral and topical medications, however, major side effects in some cases are associated with them. Based on several studies, Curcuma longa can inhibit several inflammatory enzymes mainly involved in the inflammatory process of Psoriasis. Therefore, we decided to target this well-known herbal agent with fantastic safety profile to be formulated as a novel topical microemulgel. The clinical and therapeutic benefit of this novel topical formulation was evaluated on 34 patients with mild to moderate plaque psoriasis in a randomized, prospective intra-individual, right-left comparative, placebo-controlled, double-blind clinical trial. The Dermatology Life Quality Index (DLQI) Questionnaire and Psoriasis area & severity index (PASI) score as well as photos before and after treatment was used to evaluate the outcomes. The results show that the clinical and quality of life parameters in treated lesions in comparison with untreated lesions have improved (P<0.05). The reported side effects were also recorded and were trivial. Based on our findings, the proposed microemulgel may well be considered as an alternative in some patients and most likely as an add-on therapeutic option for many patients suffering with plaque psoriasis.

Microvascular Dysfunction is Evident in the Cutaneous Circulation of Psoriatic Patients

Vascular dysfunction in conduit and resistance vessels is evident in adults with plaque psoriasis, a chronic systemic inflammatory disease. However, potential impairments of cutaneous microvascular function in psoriatic patients remain incompletely understood. We hypothesized that microvascular function would be impaired in the cutaneous circulation (non‐lesional) of psoriatic patients. One intradermal microdialysis fiber was placed in the forearm skin of 5 healthy adults (NP: 1M, 4F; 49 ± 1 yr) and 5 adults with moderate (&gt;5% body surface area affected) plaque psoriasis (P: 1M, 4F; 48 ± 1 yr). The site was perfused with lactated Ringer's while red blood cell flux was measured using laser‐Doppler flowmetry during standardized local heating (42°C) to elicit eNOS‐dependent vasodilation. NO‐dependent vasodilation was further quantified after the perfusion of 20 mM L‐NAME (nonspecific NO‐synthase inhibitor). Data were expressed as a percentage of maximum cutaneous vascular conductance (%CVCmax; 28 mM SNP). The local heating‐induced plateau was attenuated in psoriatic patients (NP: 99 ± 1 %CVCmax vs. P: 75 ± 9 %CVCmax; p&lt;0.05). Quantified eNOS‐dependent vasodilation appears to be reduced in the psoriatic group (NP: 57 ± 8 %CVCmax vs. P: 41 ± 8 %CVCmax; p=0.15). These preliminary results suggest that microvascular dysfunction is evident in psoriatic patients and may be mediated by reduced NO bioavailability. Further, the assessment of cutaneous vascular function has particular relevance for this clinical population because the skin‐related symptomology represents the outward manifestation of this systemic inflammatory disease process.FUNDING: Penn State College of HHD Grant

Hydrocortisone cream once daily plus emollient, keratolytic, keratoplastic, and antinflammatory cream in comparison with hydrocortisone twice daily for mild to moderate plaque psoriasis: An intrapatient, randomized, assessor-blinded, ultrasound evaluation

Hydrocortisone cream once daily plus emollient, keratolytic, keratoplastic, and antinflammatory cream in comparison with hydrocortisone twice daily for mild to moderate plaque psoriasis: An intrapatient, randomized, assessor-blinded, ultrasound evaluation

Clinical and laboratory parameters associated with metabolic syndrome in Turkish patients with psoriasis

To assess clinical and laboratory parameters associated with metabolic syndrome in Turkish patients with moderate or severe plaque-type psoriasis and nonpsoriatic controls. Patients with moderate or severe plaque psoriasis (patient group) or with nonpsoriatic dermatological disease (controls) were included. Waist circumference, weight, height and arterial blood pressure were measured, together with fasting blood glucose, triglyceride, high density lipoprotein (HDL), fibrinogen, homocysteine and adiponectin levels. Metabolic syndrome was diagnosed using National Cholesterol Education Program-Adult Treatment Panel III criteria. Out of 90 patients (50 with psoriasis; 40 controls), metabolic syndrome was more frequent in the patient group than in controls. In terms of metabolic syndrome parameters, only hypertension was more frequent in patients with psoriasis compared with controls. There was no statistically significant difference between the patient and control groups for obesity, hypertriglyceridaemia, HDL levels or hyperglycaemia. Fibrinogen levels were increased and adiponectin levels were decreased in the psoriasis group. No between-group difference in homocysteine levels was found. In this small study, metabolic syndrome was found to be more frequently identified in Turkish patients with psoriasis than in controls; metabolic syndrome could lead to increased cardiovascular disease risk in patients with moderate to severe psoriasis.

Good response to moderate plaque psoriasis with ustekinumab in a patient with demyelinating disease and metabolic syndrome

Good response to moderate plaque psoriasis with ustekinumab in a patient with demyelinating disease and metabolic syndrome

Patients' impressions of calcitriol for treatment of mild to moderate plaque psoriasis: Results from patient questionnaires

Patients' impressions of calcitriol for treatment of mild to moderate plaque psoriasis: Results from patient questionnaires

Efficacy and safety of topical WBI‐1001 in patients with mild to moderate psoriasis: results from a randomized double‐blind placebo‐controlled, phase II trial

There is a need for the development of novel non-steroidal topical drugs for the treatment of psoriasis. To assess the efficacy and safety of topical 1.0% WBI-1001 in patients with mild to moderate plaque psoriasis. A total of 61 patients with 1-10% body surface area (BSA) covered with plaque psoriasis and a physician's global assessment score (PGA) of 2-4 were randomized (2:1) to receive either 1% WBI-1001 in a cream formulation or placebo, applied twice daily for 12 weeks. Efficacy was evaluated using PGA, BSA and Psoriasis Area and Severity Index (PASI). The primary endpoint was the change from baseline (Day 0) in PGA at week 12. The improvement in PGA at week 12 was 62.8% for patients randomized to WBI-1001 when compared with 13.0% for patients randomized to placebo (P<0.0001). At week 12, the proportion of patients who achieved a PGA of clear or almost clear and the mean improvement in BSA were 67.5% and 79.1%, respectively, for patients randomized to WBI-1001, when compared with 4.8% (P<0.0001) and an increase of 9.4% (P<0.0001), respectively, for patients randomized to placebo. More application site adverse drug reactions were observed in patients randomized to WBI-1001 than in those randomized to placebo. These adverse drug reactions were all mild or moderate in intensity. Topical WBI-1001 induces rapid and significant improvement in patients with plaque psoriasis.

The Role of Vitamin D in Psoriasis

The function of vitamin D in regulating the inflammation, proliferation, and differentiation of keratinocytes has led to the use of topical vitamin D analogs for the treatment of plaque psoriasis. Both calcipotriene, a synthetic form of vitamin D, and calcitriol, a naturally occurring form of vitamin D, are commonly prescribed topical agents that have demonstrated significant improvement in the treatment of mild to moderate plaque psoriasis compared with vehicle alone. The most effective use of vitamin D analogs for plaque psoriasis has been in combination with topical corticosteroids. The low side-effect profile of these topical vitamin D agents also makes them an important therapeutic option for plaque psoriasis. This article summarizes the major studies involving topical vitamin D analogs for plaque psoriasis with suggestions for areas of future study.

Study on the use of omega-3 fatty acids as a therapeutic supplement in treatment of psoriasis

Previous studies have suggested a benefit for patients with plaque psoriasis when omega-3 fatty acids are added to topical treatment. This study evaluated the efficacy of a nutritional complement rich in omega-3 fatty acids in patients with mild or moderate plaque psoriasis. Thirty patients were recruited, 15 of whom were given topical treatment with tacalcitol, forming the control group. The remaining 15 patients were given topical tacalcitol and 2 capsules of Oravex® daily. Three visits, the baseline, intermediate (week 4), and final (week 8), were held over an 8-week period. The main efficacy endpoints were the Psoriasis Area and Severity Index (PASI), Nail Psoriasis Severity Index (NAPSI) and Dermatological Life Quality Index (DLQI). A clear and significant improvement was observed in all the efficacy endpoints in both groups between the baseline visit and the end visit. This improvement was significantly greater in the group treated additionally with Oravex® than in the control group. Supplementary treatment with omega-3 fatty acids complements topical treatment in psoriasis, and makes a significant contribution to reducing PASI and NAPSI and improving DLQI; and to reducing scalp lesion and pruritus, erythema, scaling, and infiltration of the treated areas.

Topical steroids versus PUVA therapy in moderate plaque psoriasis: A clinical trial along with cost analysis

Background: Psoriasis is a common chronic disease. It is estimated that between US$1.6 billion and US$3.2 billion is spent per year to treat psoriasis. Objective: To compare psoralen plus UV-A (PUVA) therapy with topical steroids in moderate plaque psoriasis. Methods: In this randomized, clinical trial with cost analysis, 88 patients with moderate plaque psoriasis were recruited in two equal groups to receive either PUVA therapy or topical steroids. The induction phase was applied for 4 months and the patients were followed-up for another 3 months, while the maintenance therapy continued. Outcome, direct cost (related to medications, phototherapy, laboratory tests, and medical consultation), indirect cost (related to transportation and other extra expenditures) and total cost (direct plus indirect costs) were compared between the two groups. Results: The outcome was equally satisfactory in both groups. The indirect cost was significantly higher in the PUVA group, while the direct and total costs as well as the patients' satisfaction rate were comparable. Recurrence was significantly more frequent in the topical group. Conclusion: Although both PUVA therapy and topical steroids are equally efficient and cost-effective in moderate plaque psoriasis, the recurrence rate is higher in the latter group.

Safety and efficacy of two regimens involving clobetasol spray, 0.05% and calcitriol ointment, 3 μg/g for moderate plaque psoriasis

Safety and efficacy of two regimens involving clobetasol spray, 0.05% and calcitriol ointment, 3 μg/g for moderate plaque psoriasis

A psoriasis-specific model to support decision making in practice – UK experience

Objectives:The balance of service provision for people with psoriasis across community and hospital sectors is inappropriate in many localities. Disease-specific models are being used by policy makers to inform public health decision making and guide their long-term budgets. The aim of the present study was to develop an interactive psoriasis model to compare the 2-year outcomes of topical treatment strategies in patients with moderately severe psoriasis in real-world settings.Research design and methods:A previously published 1-year economic analysis of the two-compound formulation (TCF) calcipotriol plus betamethasone dipropionate and other commonly used topical agents in plaque psoriasis was adapted. Literature review and an interview programme identified additional relevant data to inform model assumptions. The model estimated local psoriasis costs and resources in accord with decision makers’ priorities. A key element of the model was the facility for all default input data to be adapted to reflect local circumstance. Model validation was not undertaken. The UK experience is described.Results:Topical treatment with high-efficacy first-line therapies is a cost-effective treatment strategy in moderate plaque psoriasis. The model predicts potential savings in psoriasis care for a UK population of £126 million over 2 years if all psoriasis patients received the TCF in a community setting. A frequently used feature of the model was to identify ways of reducing inappropriate referrals to hospital, and so enabling secondary care resources to be focussed on the most resilient psoriasis cases.Conclusions:The present study psoriasis disease model could facilitate collaboration between healthcare professionals to optimise healthcare in the UK. Psoriasis management strategies in primary care can be compared in a variety of realistic clinical settings, allowing the identification of optimal treatment regimens. This model is adaptable to tailor inputs to reflect local situations, providing an attractive tool to GP commissioners. Country-specific adaptations are being researched in other European countries.

A Cost-effectiveness Comparison of Liquor Carbonis Distillate Solution and Calcipotriol Cream in the Treatment of Moderate Chronic Plaque Psoriasis

A Cost-effectiveness Comparison of Liquor Carbonis Distillate Solution and Calcipotriol Cream in the Treatment of Moderate Chronic Plaque Psoriasis

Efficacy and Tolerability of a Cosmetically Acceptable Coal Tar Solution in the Treatment of Moderate Plaque Psoriasis

Topical coal tar is a well known and effective treatment for psoriasis, but the messiness, staining, odor, and inconvenience associated with its use make patient satisfaction and compliance a challenge. To determine the efficacy, patient tolerability, and cosmetic acceptability of a new topical liquor carbonis distillate (LCD) 15% solution compared with calcipotriene (calcipotriol) cream in patients with moderate, chronic plaque psoriasis. A randomized, single-blind, active-controlled, parallel-group, clinical trial consisting of a 12-week treatment phase and a 6-week post-treatment follow-up phase. Outpatient dermatology research unit in an academic hospital. Sixty adults with moderate, chronic plaque psoriasis (3-15% body surface area affected) not receiving other psoriasis therapies. Patients were randomized to apply either an LCD 15% solution (Psorent) or a commercially available calcipotriene 0.005% cream (Dovonex) to their psoriasis areas (excluding the head) twice daily at home for 12 weeks. A blinded investigator evaluated the patients' psoriasis using a modified Psoriasis Area and Severity Index (PASI) that excluded the head, and a Physician's Global Assessment (PGA) scale at weeks 0 (baseline), 2, 4, 8, and 12 (end of treatment), and 18 (6 weeks after treatment was withdrawn). Patients assessed their psoriasis symptoms and quality of life and completed a cosmetic acceptability survey about their medication. The changes in the baseline PASI scores after 12 weeks of treatment were compared between LCD and calcipotriene groups. Additional comparisons were performed for success rates during treatment (PASI 75 and PASI 50), changes in PGA scores, patient-reported psoriasis symptom scores, patients' quality-of-life scores, and recurrence rates during post-treatment follow-up. Both treatment groups showed improvement in psoriasis severity and quality of life. However, the LCD group had greater mean reductions in PASI scores: 58% vs 37% in the calcipotriene group (p < 0.05) at week 12. Additionally, the LCD group had more patients (14/27) with absent or minimal psoriasis on the PGA scale than the calcipotriene group (6/28) by the end of treatment (p < 0.05). LCD-treated patients also maintained their improvement better than calcipotriene-treated patients through week 18 after treatment was withdrawn for 6 weeks. Both treatments were well tolerated and cosmetically acceptable to patients. The newly formulated LCD solution, applied twice daily at home for 12 weeks, was more effective and as well tolerated and cosmetically acceptable as the calcipotriene cream over 12 weeks of treatment and 6 weeks of follow-up. The LCD solution is a patient-accepted and effective corticosteroid-sparing treatment alternative for psoriasis patients.

New drugs: Ustekinumab, tocilizumab, and telavancin hydrochloride

Agent for psoriasis Psoriasis is an autoimmune disease characterized by inflammatory skin lesions/plaques that are often painful and can be debilitating. Although milder forms of psoriasis can often be effectively treated with topical corticosteroids and other topically applied agents, moderate to severe forms of the disease often require systemic therapy or phototherapy. Advances in the treatment of psoriasis have included the use of medications that have immunosuppressive activity such as methotrexate; cyclosporine; alefacept (Amevive), which interferes with T-cell activation; and the tumor necrosis factor (TNF) antagonists etanercept (Enbrel), adalimumab (Humira), and infliximab (Remicade). Interleukin (IL)-12 and -23 are naturally occurring proteins that are involved in the psoriatic inflammatory process by activating natural killer cells and T-cells. Ustekinumab (Stelara—Centocor Ortho Biotech) is a human monoclonal antibody that is the first medication to selectively bind to these cytokines. It binds with high affinity to the p40 protein subunit of IL-12 and -23, thereby preventing them from binding with their respective receptors and resulting in a decreased inflammatory response. The new drug is indicated for the treatment of adult patients with moderate or severe plaque psoriasis who are candidates for phototherapy or systemic therapy. The efficacy of ustekinumab was demonstrated in two placebo-controlled studies in which approximately 70% of the patients treated with the drug experienced at least a 75% reduction in the Psoriasis Area and Severity Index (PASI) score (PASI 75) after two doses compared with less than 5% of those receiving placebo. In one of these studies, patients were evaluated for a longer period and approximately 90% of the patients having an initial reduction in PASI score of at least 75% maintained this response through 1 year of treatment. In a study in which ustekinumab was compared with etanercept, 68% and 74% of patients treated with 45 and 90 mg ustekinumab dosages, respectively, experienced at least a 75% reduction in PASI score compared with 57% of the patients treated with etanercept. Of the patients who did not have a response to etanercept, almost 50% had at least a 75% reduction in PASI score within 12 weeks following subsequent treatment with ustekinumab. The risks and adverse events associated with the use of ustekinumab are generally similar to those of the TNF antagonists. Of greatest concern is the potential for serious infection, and treatment with ustekinumab should not be initiated in patients with a clinically important active infection. If a serious infection develops during treatment, treatment with ustekinumab should be suspended until the infection is adequately treated or resolves. Patients should be evaluated for the presence of a tuberculosis (TB) infection before initiating treatment with ustekinumab. The drug should not be used in patients with active TB, and if latent TB is identified, antitubercular treatment should be initiated before administering ustekinumab. Individuals who have a genetic deficiency of IL-12 and -23 are at greater risk of disseminated infections caused by mycobacteria, salmonella, and Bacillus CalmetteGuerin (BCG) vaccinations. Whether patients experiencing inhibition of these ILs as a result of ustekinumab treatment will be more vulnerable to these infections is not known. However, it is recommended that BCG vaccines not be administered during treatment with ustekinumab or for 1 year before initiating treatment or 1 year following discontinuation of treatment. Before initiating treatment with ustekinumab, patients should have already received the immunizations recommended by current guidelines, and they should not receive live vaccines during treatment. Like other medications that exhibit an immunosuppressant action, ustekinumab may increase the risk of malignancies. The safety of its use in patients who have a known malignancy or a history of malignancy has not been evaluated. In the clinical studies with ustekinumab, which included more than 3,500 patients, one patient developed reversible posterior leukoencephalopathy syndrome (RPLS). Treatment was discontinued, and the patient fully recovered with appropriate management. If neurologic or other manifestations suggestive of RPLS occur in patients treated with the new drug, therapy should be discontinued. The adverse events experienced most often in the clinical studies with ustekinumab include nasopharyngitis (7%), headache (5%), upper respiratory tract infection (4%), and fatigue (3%). As with all biological therapies, a concern exists regarding immunogenicity. Because ustekinumab has such a long half-life and its presence in the blood interferes with the antibody assay, many of the test results were inconclusive. Of the approximately 2,000 patients screened, less than 5% had positive antibody results, indicating a low risk of immunogenicity. Ustekinumab is classified in Pregnancy Category B and should only be

A prospective, randomized clinical trial comparing topical aloe vera with 0.1% triamcinolone acetonide in mild to moderate plaque psoriasis

Topical aloe vera (AV) has been used to treat various skin conditions, including psoriasis, with good results. This study aims to compare the efficacy of AV and 0.1% triamcinolone acetonide (TA) in mild to moderate plaque psoriasis. A randomized, comparative, double-blind, 8-week study was designed. Eighty patients randomly received AV or 0.1% TA cream and their clinical response were evaluated using the Psoriasis Area Severity Index (PASI) and the Dermatology Life Quality Index (DLQI). After 8 weeks of treatment, the mean PASI score decreased from 11.6 to 3.9 (-7.7) in the AV group and from 10.9 to 4.3 (-6.6) in the TA group. Between-group difference was 1.1 (95% confidence interval -2.13, -0.16, P = 0.0237). The mean DLQI score decreased from 8.6 to 2.5 (-6.1) in the AV group and from 8.1 to 2.3 (-5.8) in the TA group. Between-group difference was 0.3 (95% confidence interval -1.18, -0.64, P = 0.5497). There was no follow-up period after the 8-week treatment. AV cream may be more effective than 0.1% TA cream in reducing the clinical symptoms of psoriasis; however, both treatments have similar efficacy in improving the quality of life of patients with mild to moderate psoriasis.

Vitamin D analogue-based therapies for psoriasis

Topical vitamin D3 analogues are a mainstay of treatment in mild to moderate plaque psoriasis. Vitamin D3 analogues exert their effect in psoriasis via binding nuclear vitamin D3 receptors on genes involved in cellular proliferation, differentiation and inflammation. Currently available synthetic vitamin D3 analogues include calcipotriol, maxacalcitol, tacalcitol and calcitriol. These agents are only minimally systemically absorbed and therefore have few systemic side effects. Local irritation is the most frequently noted side effect and can be managed by combining vitamin D3 analogues with other topical or systemic therapies, such as topical corticosteroids or narrow-band UVB phototherapy. The use of a vitamin D agent helps improve the efficacy of topical corticosteroids for psoriasis and helps minimize the potential for adverse events associated with topical corticosteroid treatment. Care should be taken when combining with other topical therapies due to potential inactivation of either agent. Topical vitamin D3 analogues can be a cost-effective addition to a psoriasis treatment regimen, especially when compliance is encouraged by the tolerability of these agents and more costly systemic agents are avoided.

Diminished Neural and Cognitive Responses to Facial Expressions of Disgust in Patients with Psoriasis: A Functional Magnetic Resonance Imaging Study

Psoriasis produces significant psychosocial disability; however, little is understood about the neurocognitive mechanisms that mediate the adverse consequences of the social stigma associated with visible skin lesions, such as disgusted facial expressions of others. Both the feeling of disgust and the observation of disgust in others are known to activate the insula cortex. We investigated whether the social impact of psoriasis is associated with altered cognitive processing of disgust using (i) a covert recognition of faces task conducted using functional magnetic resonance imaging (fMRI) and (ii) the facial expression recognition task (FERT), a decision-making task, conducted outside the scanner to assess the ability to recognize overtly different intensities of disgust. Thirteen right-handed male patients with psoriasis and 13 age-matched male controls were included. In the fMRI study, psoriasis patients had significantly (P<0.005) smaller signal responses to disgusted faces in the bilateral insular cortex compared with healthy controls. These data were corroborated by FERT, in that patients were less able than controls to identify all intensities of disgust tested. We hypothesize that patients with psoriasis, in this case male patients, develop a coping mechanism to protect them from stressful emotional responses by blocking the processing of disgusted facial expressions.