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1.
Psoriasis in those planning a family, pregnant or breast-feeding. The Australasian Psoriasis Collaboration.
Rademaker, M, Agnew, K, Andrews, M, Armour, K, Baker, C, Foley, P, Frew, J, Gebauer, K, Gupta, M, Kennedy, D, et al
The Australasian journal of dermatology. 2018;(2):86-100
Abstract
The Australasian Psoriasis Collaboration has reviewed the evidence for managing moderate to severe psoriasis in those who are pregnant or are breast-feeding, or planning a family. The severity of the psoriasis, associated comorbidities and specific anti-psoriasis treatment, along with other exposures, can have a deleterious effect on pregnancy outcomes. Psoriasis itself increases the risk of preterm and low birthweight babies, along with spontaneous and induced abortions, but no specific birth defects have been otherwise demonstrated. The baseline risk for a live born baby to have a major birth defect is 3%, and significant neuro-developmental problem is 5%. In Australia, pregnant women with psoriasis are more likely to be overweight or obese, depressed, or smoke in their first trimester, and are also less likely to take prenatal vitamins or supplements. Preconception counselling to improve maternal, pregnancy and baby health is therefore strongly encouraged. The topical and systemic therapies commonly used in psoriasis are each discussed separately, with regards to pregnancy exposure, breast-feeding and effects on male fertility and mutagenicity. The systemic therapies included are acitretin, adalimumab, apremilast, certolizumab, ciclosporin, etanercept, infliximab, ixekizumab, methotrexate, NBUVB, prednisone, PUVA, secukinumab and ustekinumab. The topical therapies include dithranol (anthralin), calcipotriol, coal tar, corticosteroids (weak, potent and super-potent), moisturisers, salicylic acid, tacrolimus, and tazarotene. As a general recommendation, effective drugs that have been widely used for years are preferable to newer alternatives with less foetal safety data. It is equally important to evaluate the risks of not treating, as severe untreated disease may negatively impact both mother and the foetus.
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2.
What do Cochrane systematic reviews say about interventions for treating psoriasis?
Pacheco, RL, Hosni, ND, Latorraca, COC, Martimbianco, ALC, Pachito, DV, Yarak, S, Riera, R
Sao Paulo medical journal = Revista paulista de medicina. 2018;(4):354-360
Abstract
CONTEXT AND OBJECTIVE Psoriasis is a common chronic inflammatory skin disease characterized by abnormal and increased growth of the cells that produce keratin and abnormal functioning of the immune system. We aimed to summarize the evidence available regarding interventions for patients with psoriasis. DESIGN AND SETTING Review of systematic reviews, developed in the Discipline of Evidence-Based Medicine, Escola Paulista de Medicina, Universidade Federal de São Paulo. METHODS A systematic search was conducted to identify Cochrane systematic reviews that fulfilled the eligibility criteria. Two authors screened titles and abstracts that had been retrieved through the search strategy. The results from all the Cochrane systematic reviews that were included were summarized and presented in a narrative synthesis. RESULTS We included six Cochrane systematic reviews assessing interventions for treating psoriasis. The findings from high-quality evidence were that (a) etanercept reduced the psoriasis severity index, compared with placebo and (b) steroids plus vitamin D, compared with vitamin D alone, improved the skin clearance rate, as assessed by investigators, but was associated with a higher proportion of participants who dropped out due to adverse events. For all other comparisons, the quality of the evidence ranged from moderate to very low. CONCLUSION This review included six Cochrane systematic reviews that provided evidence ranging in quality from unknown to high, regarding management of psoriasis. Further randomized controlled trials are imperative to reduce the uncertainties relating to several treatments that are already used in clinical practice.
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3.
Combining Biologics in Inflammatory Bowel Disease and Other Immune Mediated Inflammatory Disorders.
Hirten, RP, Iacucci, M, Shah, S, Ghosh, S, Colombel, JF
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2018;(9):1374-1384
Abstract
Current therapies used in the treatment of inflammatory bowel disease (IBD) are not effective in all patients. Biologic agents result in approximately 40% remission rates at 1 year in selected populations, prompting a growing interest in combining biologic therapy to improve outcomes. There are limited published data regarding the efficacy and safety of combination targeted therapy in IBD specifically, which include only 1 exploratory randomized control trial and 3 case reports or series. This review evaluates the published literature regarding this therapeutic paradigm in IBD and its extensive utilization in the treatment of other immune-mediated inflammatory disorders. The combination of biologic therapies demonstrates variable degrees of efficacy and highlights some safety concerns, depending upon the agents used and the disease state treated. A trial (Clinical Trials.gov Identifier: NCT02764762) combining vedolizumab and adalimumab is currently underway evaluating the effectiveness and safety of this approach in patients with Crohn's disease, which should provide further insight into this treatment concept. While combination biologic therapy is an attractive strategy, the lack of consistent superior efficacy as well as safety concerns militates the need for further trials prior to its general application in IBD.
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4.
Can an app supporting psoriasis patients improve adherence to topical treatment? A single-blind randomized controlled trial.
Svendsen, MT, Andersen, F, Andersen, KH, Andersen, KE
BMC dermatology. 2018;(1):2
Abstract
BACKGROUND Topical corticosteroid or corticosteroid/calcipotriol preparations are recommended first-line topical treatments of psoriasis, but a main cause for the lack of efficacy of topical treatments is considered low rates of adherence to topical drugs. Patient support by the use of applications (apps) for smartphones is suggested to improve medical adherence. METHODS/DESIGN Design: An investigator-initiated, single-center, single-blind, parallel-group, phase-4 clinical superiority randomized controlled trial (RCT). PARTICIPANTS 134 patients 18 to 75 years of age with mild-to-moderate psoriasis, who are capable of reading English language, own a smartphone, and are candidates for the study drug calcipotriol and betamethasone dipropionate (Cal/BD) cutaneous foam once daily prn (pro re nata). INTERVENTION A 28-day adherence-supporting app providing compulsory daily treatment reminders that pop-up on the smartphone screen with a short alert sound. The app synchronizes through Bluetooth® to an electronic monitor (EM) attached to the medication canister. The EM contains a chip registering the amount of foam, day and time the patient use the foam dispenser. The information is displayed in a diary that shows the amount of Cal/BD cutaneous foam used and the number of applied treatment sessions. The app has an optional diary with the patient's rating of symptoms. Non-intervention: Use of Cal/BD cutaneous foam and EM without the app. All participants are prescribed Cal/BD cutaneous foam prn for the entire study period. Primary outcome obtained in week 4: rates of adherence measured by patient report, weight of medication canisters, and number of treatment sessions measured by the EM. Secondary outcomes obtained at baseline, weeks 4, 8, and 26: Lattice System Physician's Global Assessment (LS-PGA) and Dermatology Quality of Life Index (DLQI). DISCUSSION This trial tests of whether an app can improve rates of adherence to a topical antipsoriatic drug. If the app improves rates of adherence and reduces the burden of psoriasis in a clinically significant way, the app could easily be implemented as a standard routine of care in the clinic. TRIAL REGISTRATION NCT02858713 , registered on August 3, 2016. EudraCT number 2016-002143-42.
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Turmeric tonic as a treatment in scalp psoriasis: A randomized placebo-control clinical trial.
Bahraini, P, Rajabi, M, Mansouri, P, Sarafian, G, Chalangari, R, Azizian, Z
Journal of cosmetic dermatology. 2018;(3):461-466
Abstract
BACKGROUND Psoriasis is an autoimmune and recurrent chronic inflammatory skin disorder with a strong genetic basis. The characteristic features are hyperproliferation of keratinocytes, leading to redness, thickening, and scaling of the epidermis followed by itching and the appearance of lesions, which in most cases can affect the patients both medically and psychologically. The scalp is one of the most common sites for psoriasis. This condition is predominantly managed with steroids, which are associated with various side effects. Turmeric (Curcuma longa L.), a spice commonly used throughout the world, has been shown to exhibit anti-inflammatory, antimicrobial, antioxidant, and antineoplastic properties. It has been reported to exhibit inhibitory activity on potassium channels in T cells and plays a key role in psoriasis. AIM: We were prompted to investigate the turmeric tonic as an immune modulation and anti-inflammatory therapy on scalp psoriasis. METHOD Forty patients with mild-to-moderate scalp psoriasis who fulfilled the inclusion criteria were randomly allocated into two groups. The case group received turmeric tonic twice a day for 9 weeks, whereas the other group received a placebo applied in the same manner. Patients were evaluated at the following points: baseline, weeks 3, 6, and 9. The dermatology life quality index (DLQI) questionnaire and PASI (psoriasis area & severity index) scores, as well as medical photos before, during and after treatment were also evaluated. The probable adverse effects were also recorded and reported. RESULTS Compared to the placebo, turmeric tonic significantly reduced the erythema, scaling and induration of lesions (PASI score), and also improved the patients' quality of life (P value < .05). CONCLUSIONS The clinical effects of turmeric tonic on scalp psoriasis were satisfactory overall. This formulation could be considered as a treatment for scalp psoriasis.
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The Evolution of Topical Formulations in Psoriasis.
Kuehl, B, Shear, NH
Skin therapy letter. 2018;(4):5-9
Abstract
Most people with mild-to-moderate psoriasis manage their disease with topical therapies. However, adherence to topical treatment remains a challenge, as the daily application creates a significant treatment burden. New topical therapeutic options need to offer higher efficacy and better patient acceptability, including easier application, to reduce treatment burden and enhance patient adherence. Topical foam vehicles are innovative alternatives to creams and ointments, addressing many patient challenges with traditional vehicles. Well-designed foam vehicles are easily spread over large areas of the skin, while importantly not leaving a greasy or oily film on the skin after application. Calcipotriol/betamethasone diproprionate aerosol foam is a new psoriasis treatment option that is rapidly effective, offers greater efficacy versus ointment and gel formulations, and has been shown to increase patient treatment satisfaction. Hence, by addressing the several crucial unmet clinical needs in patients with mild-to-moderate psoriasis, this optimized foam formulation is poised to improve treatment follow-through.
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7.
Clinical use of dimethyl fumarate in moderate-to-severe plaque-type psoriasis: a European expert consensus.
Mrowietz, U, Barker, J, Boehncke, WH, Iversen, L, Kirby, B, Naldi, L, Reich, K, Tanew, A, van de Kerkhof, PCM, Warren, RB
Journal of the European Academy of Dermatology and Venereology : JEADV. 2018;:3-14
Abstract
Fumaric acid esters (FAEs) are a group of small molecules that were first investigated for the treatment of psoriasis in 1959. The first fumarate-based drug - Fumaderm® - was approved in Germany in 1994 for severe psoriasis and then in 2008, the label was expanded to include moderate psoriasis. Fumaderm is a combination of different FAEs: dimethyl fumarate (DMF), which is regarded as the main active component, plus calcium, magnesium and zinc salts of monoethyl fumarate (MEF). FAEs are the most frequently used first-line systemic psoriasis treatment in Germany, with an overall treatment experience comprising more than 220 000 patient-years. FAEs have demonstrated good, sustained clinical efficacy with an acceptable safety profile for the long-term treatment of patients with moderate-to-severe psoriasis. Indeed, the European S3-Guideline on the systemic treatment of Psoriasis vulgaris recommends FAEs for induction and long-term treatment. Until recently, FAEs were only licensed (for the psoriasis indication) in Germany, but were imported to many other European countries, such as The Netherlands, UK, Ireland, Austria and Italy, for the treatment of psoriasis. In 2017, the European Medicines Agency (EMA) approved Skilarence® , a new oral formulation of DMF, for the treatment of adult patients with moderate-to-severe chronic plaque psoriasis in need of systemic therapy. Skilarence only contains DMF and is the first FAE for the treatment of psoriasis that has been approved by the EMA. This approval has given rise to a new oral treatment option for patients with moderate-to-severe plaque psoriasis across Europe. Here, we report the results of an expert meeting which was convened to deliver clinician-agreed consensus and real-world guidance on the clinical use of DMF in moderate-to-severe chronic plaque psoriasis. Guidance on appropriate patient selection, DMF dosage considerations, monitoring and side-effect management is offered based upon available evidence and collective real-world clinical experience.
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Factors influencing cardiometabolic risk profile in patients with psoriasis.
Curcó, N, Barriendos, N, Barahona, MJ, Arteaga, C, García, M, Yordanov, S, De La Barrera, O, Prat, C, Vives, P, Giménez, N
The Australasian journal of dermatology. 2018;(2):e93-e98
Abstract
BACKGROUND Psoriasis has been associated with metabolic syndrome and with an increased cardiovascular risk especially in patients with severe disease. The goal of this study was to estimate the prevalence of metabolic syndrome and other cardiovascular risk factors and its association with the psoriasis severity, sex and age. METHODS Consecutive patients with psoriasis were enrolled in a prospective study over a 1-year period. Blood samples were collected. Psoriasis area and severity index (PASI) and body surface area scores and two dermatology quality of life (DQOL) questionnaires were used to evaluate psoriasis severity and the impact of the disease. RESULTS Altogether 178 patients were included, of whom 44% had moderate-severe psoriasis. The overall prevalence of metabolic syndrome was 30% (men 34%, women 26%) without significant differences between patients with severe and mild disease. Age and menopause appeared to increase the risk for metabolic syndrome. Patients with severe psoriasis smoked more heavily, were more likely to have diabetes or insulin resistance and had higher homocysteine and lower high density lipoprotein cholesterol (HDL-C) levels than patients with mild psoriasis (P < 0.05). In women, a higher waist circumference was observed. Women had higher HDL-C levels and lower smoking and alcohol consumption rates. In accordance with the systematic coronary risk evaluation system, 18% of the patients had a high 10-year risk of fatal cardiovascular disease. CONCLUSIONS Psoriasis severity was associated with diabetes, insulin-resistance, smoking habit and higher cardiovascular risk. Metabolic syndrome was related to age and menopause but not to psoriasis severity.
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Tazarotene Revisited: Safety and Efficacy in Plaque Psoriasis and Its Emerging Role in Treatment Strategy.
Tanghetti, E, Lebwohl, M, Stein Gold, L
Journal of drugs in dermatology : JDD. 2018;(12):1280-1287
Abstract
Background: Psoriasis is a chronic, immune-mediated disease that varies widely in its clinical expression. Treatment options focus on relieving symptoms, reducing inflammation, induration, and scaling, and controlling the extent of the disease. While significant data on tazarotene in psoriasis has been available for over 20 years, its main utility is in acne. Objective: To review the clinical studies with tazarotene in psoriasis and establish its future role in the management of this chronic, incurable condition. Methods: An English language literature review was performed utilizing Medline, EMBASE, and the Web of Science to identify relevant articles, both clinical trials and reviews. Results: Tazarotene is a very effective treatment for plaque psoriasis, with significant reductions in both plaque elevation and scaling after 12 weeks. Efficacy appears to be dose and formulation dependent, and erythema less responsive. Tazarotene sustains clinical response posttreatment and may have an important role in maintenance therapy. The most common side effect is mild-to-moderate local irritation, which limited its role as a single agent for psoriasis. Efficacy is enhanced through combination with topical corticosteroids (TCS). Tazarotene may circumvent the problem of TCS tachyphylaxis, due to its sustained efficacy and provide tolerability benefits; tazarotene increases epidermal thickness and may reduce the risk of steroid-induced atrophy. In addition, tazarotene-induced irritation is reduced by the anti-inflammatory effect of TCS. A new fixed combination, well-tolerated tazarotene/halobetasol topical formulation is now available, which provides synergistic efficacy that is both rapid and sustained posttreatment. Conclusions: Tazarotene is a highly effective psoriasis treatment whose efficacy and tolerability can be enhanced through combination therapy with TCS, and a new fixed combination topical formulation of tazarotene and halobetasol may provide an optimal management approach. J Drugs Dermatol. 2018;17(12):1280-1287.
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Effect of RNA Interference Targeting STAT3 Gene Combined with Ultrasonic Irradiation and SonoVue Microbubbles on Proliferation and Apoptosis in Keratinocytes of Psoriatic Lesions.
Ran, LW, Wang, H, Lan, D, Jia, HX, Yu, SS
Chinese medical journal. 2018;(17):2097-2104
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Abstract
BACKGROUND Signal transducer and activator of transcription 3 (STAT3) was strongly expressed and activated in psoriatic keratinocytes (KCs) and correlated with the severity of psoriasis. The study aimed to investigate the effects of STAT3 small interfering RNA (siRNA) combined with ultrasonic irradiation and SonoVue microbubbles on the proliferation and apoptosis in KCs of psoriatic lesions and the relative mechanisms. METHODS Psoriatic KCs were transfected under four experimental conditions: (1) STAT3 siRNA carried by Lipofectamine 3000 combined with ultrasonic irradiation and SonoVue microbubbles (LUS group); (2) STAT3 siRNA only carried by Lipofectamine 3000 (L group); (3) the negative control of siRNA carried by Lipofectamine 3000 combined with ultrasonic irradiation and SonoVue microbubbles (siRNA-NC); (4) not treated as Blank. Cell Counting Kit-8 assay was used to evaluate the cell proliferation. Cell cycle analysis was detected with cycle test Plus DNA reagent kit associated with flow cytometer. FITC Annexin V apoptosis detection kit associated with flow cytometer was applied for apoptosis analysis. Fluo calcium indicator associated with flow cytometer was used to analyze intracellular free calcium concentration ([Ca2+]i). The expressions of cyclin D1 and Bcl-xL were detected both at the mRNA level by real-time reverse transcription-polymerase chain reaction (RT-PCR) and at the protein level by Western blotting. The obtained data were statistically evaluated by two-way analysis of variance. RESULTS STAT3 siRNA inhibited the growth of KCs in a time-dependent manner showing the highest proliferation inhibition in LUS group with proliferation ratio of 45.38% ± 5.85% at 72h (P < 0.05 vs. L group, siRNA-NC, or Blank). STAT3 siRNA induced an altered cell cycle distribution of KCs showing the highest increases in G2/M-phase population up to 18.06% ± 0.36% in LUS group (P < 0.05 vs. L group, siRNA-NC, or Blank). STAT3 siRNA induced late apoptosis of KCs with the highest late apoptosis percentage of 22.87% ± 1.28% in LUS group (P < 0.05 vs. L group, siRNA-NC, or Blank). STAT3 siRNA induced the elevation of [Ca2+]iof KCs with the highest calcium fluorescence intensity mean of 1213.67 ± 60.51 in LUS group (P < 0.05 vs. L group, siRNA-NC, or Blank). STAT3 siRNA induced the downregulation of cyclin D1 and Bcl-xL expressions of KCs at mRNA and protein levels with the lowest expressions in LUS group with cyclin D1 expression of 51.81% ± 9.58% and 70.17% ± 4.22% at mRNA level and at protein level, respectively, and with Bcl-xL expression of 37.58% ± 4.92% and 64.06% ± 7.78% at mRNA level and at protein level, respectively (P < 0.05 vs. L group, siRNA-NC, or Blank). CONCLUSIONS STAT3 siRNA inhibited the growth and induced the apoptosis in psoriatic KCs likely partly through altering cell cycle distribution, elevating [Ca2+]i, and downregulating cyclin D1 and Bcl-xL expressions. Silencing the target gene STAT3 in psoriatic KCs with siRNA combined with ultrasonic irradiation and microbubbles would contribute to a significant innovation as a new clinical therapy for psoriasis.