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Investigation of water bonding status of normal and psoriatic skin in vivo using diffuse reflectance spectroscopy.
Yang, CC, Yen, YY, Hsu, CK, Cheng, NY, Tzeng, SY, Chou, SJ, Chang, JM, Tseng, SH
Scientific reports. 2021;(1):8901
Abstract
Psoriasis affects more than 125 million people worldwide, and the diagnosis and treatment efficacy evaluation of the disease mainly rely on clinical assessments that could be subjective. Our previous study showed that the skin erythema level could be quantified using diffuse reflectance spectroscopy (DRS), and the hemoglobin concentration of most psoriatic lesion was higher than that of its adjacent uninvolved skin. While the compromised epidermal barrier function has been taken as the major cause of clinical manifestation of skin dryness and inflammation of psoriasis, very few methods can be used to effectively evaluate this function. In this study, we investigate the near infrared spectroscopic features of psoriatic (n = 21) and normal (n = 21) skin that could link to the epidermal barrier function. From the DRS measurements, it was found that the water bonding status and light scattering properties of psoriasis are significantly different from those of uninvolved or normal skin. The connection between these parameters to the epidermal barrier function and morphology will be discussed. Our results suggest that objective evaluation of epidermal barrier function of psoriasis could be achieved using a simple DRS system.
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Twice-weekly topical calcipotriene/betamethasone dipropionate foam as proactive management of plaque psoriasis increases time in remission and is well tolerated over 52 weeks (PSO-LONG trial).
Lebwohl, M, Kircik, L, Lacour, JP, Liljedahl, M, Lynde, C, Mørch, MH, Papp, KA, Perrot, JL, Gold, LS, Takhar, A, et al
Journal of the American Academy of Dermatology. 2021;(5):1269-1277
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BACKGROUND Topical psoriasis treatment relies on a reactive rather than a long-term proactive approach to disease relapse. OBJECTIVE Assess long-term efficacy and safety of proactive psoriasis management with twice-weekly calcipotriene 0.005%/betamethasone dipropionate 0.064% (Cal/BD) foam. METHODS Phase III trial (NCT02899962) included a 4-week open-label lead-in phase (Cal/BD foam once daily) and a 52-week, randomized, double-blind, maintenance phase. A total of 545 patients achieved treatment success (physician's global assessment "clear"/"almost clear," ≥2-grade improvement from baseline) and were randomized to proactive management (Cal/BD foam; n = 272) or reactive management (vehicle foam; n = 273) twice-weekly, with rescue treatment of Cal/BD foam once daily for 4 weeks upon relapse. Primary endpoint was time to first relapse (physician's global assessment "mild" or higher). RESULTS A total of 251 randomized patients (46.1%) completed the trial. Median time to first relapse was 56 days (proactive) and 30 days (reactive). Patients in the proactive group had an additional 41 days in remission compared with the reactive group over 1 year (P < .001). Number of relapses per year of exposure was 3.1 (proactive) and 4.8 (reactive). Cal/BD foam was well tolerated. LIMITATIONS Maintenance phase dropout rate (53.9%) was within the expected range but provides challenges in statistical analysis. CONCLUSION Long-term proactive management with Cal/BD foam demonstrated superior efficacy vs reactive management.
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Long-term safety results from a phase 3 open-label study of a fixed combination halobetasol propionate 0.01% and tazarotene 0.045% lotion in moderate-to-severe plaque psoriasis.
Lebwohl, MG, Sugarman, JL, Gold, LS, Pariser, DM, Lin, T, Pillai, R, Martin, G, Harris, S, Israel, R
Journal of the American Academy of Dermatology. 2019;(1):282-285
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Safety and efficacy of a fixed combination of halobetasol and tazarotene in the treatment of moderate-to-severe plaque psoriasis: Results of 2 phase 3 randomized controlled trials.
Gold, LS, Lebwohl, MG, Sugarman, JL, Pariser, DM, Lin, T, Martin, G, Pillai, R, Israel, R, Ramakrishna, T
Journal of the American Academy of Dermatology. 2018;(2):287-293
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BACKGROUND Topical corticosteroids are the mainstay of psoriasis treatment, with long-term safety considerations limiting their use. Combining them with tazarotene may optimize their efficacy and minimize safety and tolerability concerns. OBJECTIVE To investigate the safety and efficacy of halobetasol propionate 0.01% plus tazarotene 0.045% (HP/TAZ) lotion in moderate-to-severe plaque psoriasis. METHODS Two multicenter, randomized, double-blind, vehicle-controlled phase 3 studies (N = 418) were conducted. Subjects were randomized (2:1) to HP/TAZ lotion or vehicle once daily for 8 weeks with a 4-week follow-up. The primary efficacy assessment end point was treatment success (at least a 2-grade improvement from baseline in Investigator's Global Assessment score and a score of clear or almost clear). Safety and treatment-emergent adverse events were evaluated throughout. RESULTS HP/TAZ lotion demonstrated statistically significant superiority over vehicle within as few as 2 weeks. By week 8, 35.8% (study 1) and 45.3% (study 2) of subjects were treatment successes compared with 7.0% and 12.5% of those treated with vehicle (P < .001). HP/TAZ lotion was also superior in reducing signs and symptoms of psoriasis and body surface area affected by psoriasis. The most frequently reported treatment-related adverse events were contact dermatitis (6.3%), application site pain (2.6%), and pruritus (2.2%). LIMITATIONS Studies did not include subjects with more than 12% of their body surface area affected by psoriasis. CONCLUSIONS HP/TAZ lotion was associated with significant reductions in the severity of the clinical signs of psoriasis, with no safety concerns.
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Efficacy and Safety of Calcipotriol Plus Betamethasone Dipropionate Aerosol Foam Compared with Betamethasone 17-Valerate-Medicated Plaster for the Treatment of Psoriasis.
Queille-Roussel, C, Rosen, M, Clonier, F, Nørremark, K, Lacour, JP
Clinical drug investigation. 2017;(4):355-361
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BACKGROUND Fixed combination calcipotriol as hydrate (Cal) 50 µg/g plus betamethasone as dipropionate (BD) 0.5 mg/g aerosol foam is an alcohol-free treatment for psoriasis. Betamethasone 17-valerate 2.25 mg (BV)-medicated plasters are recommended for treating psoriasis plaques localized in difficult-to-treat (DTT; elbow, knee, anterior face of the tibia) areas. OBJECTIVE The aim of this study was to compare the efficacy of Cal/BD foam with BV-medicated plaster in patients with plaque psoriasis. METHODS In this phase IIa, randomized, single-center, investigator-blinded, 4-week study, both Cal/BD foam and BV-medicated plaster were applied once daily to six test sites (three for each treatment). The primary efficacy endpoint was absolute change in total clinical score (TCS; sum of erythema, scaling, and infiltration); secondary endpoints were changes from baseline in each individual clinical score, ultrasonographic changes (total skin and echo-poor band thickness), and safety; and post hoc analysis was change from baseline in TCS on DTT areas. RESULTS Thirty-five patients were included. Least-squares mean change in TCS from baseline was significantly greater for Cal/BD foam (-5.8) than BV-medicated plaster (-3.7; difference -2.2; 95% confidence interval -2.6 to -1.8; p < 0.001); greater changes for Cal/BD foam were observed from day 8 for each clinical sign. Absolute total skin and echo-poor band thickness change was significantly greater for Cal/BD foam than for BV-medicated plaster (both p < 0.001). Post hoc analyses showed that Cal/BD foam was significantly more effective than BV-medicated plaster on DTT areas after 4 weeks (p < 0.001), and both treatments were well tolerated. CONCLUSION Cal/BD foam demonstrated superior efficacy versus BV-medicated plasters, including on DTT areas, in patients with plaque psoriasis. CLINICAL TRIAL REGISTRATION NUMBER NCT02518048.
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Safety and pharmacodynamics of dalazatide, a Kv1.3 channel inhibitor, in the treatment of plaque psoriasis: A randomized phase 1b trial.
Tarcha, EJ, Olsen, CM, Probst, P, Peckham, D, Muñoz-Elías, EJ, Kruger, JG, Iadonato, SP
PloS one. 2017;(7):e0180762
Abstract
BACKGROUND Dalazatide is a specific inhibitor of the Kv1.3 potassium channel. The expression and function of Kv1.3 channels are required for the function of chronically activated memory T cells, which have been shown to be key mediators of autoimmune diseases, including psoriasis. OBJECTIVE The primary objective was to evaluate the safety of repeat doses of dalazatide in adult patients with mild-to-moderate plaque psoriasis. Secondary objectives were to evaluate clinical proof of concept and the effects of dalazatide on mediators of inflammation in the blood and on chronically activated memory T cell populations. METHODS Patients (n = 24) were randomized 5:5:2 to receive dalazatide at 30 mcg/dose, 60 mcg/dose, or placebo twice weekly by subcutaneous injection (9 doses total). Safety was assessed on the basis of physical and neurological examination and laboratory testing. Clinical assessments included body-surface area affected, Psoriasis Area and Severity Index (PASI), and investigator and patient questionnaires. RESULTS The most common adverse events were temporary mild (Grade 1) hypoesthesia (n = 20; 75% placebo, 85% dalazatide) and paresthesia (n = 15; 25% placebo, 70% dalazatide) involving the hands, feet, or perioral area. Nine of 10 patients in the 60 mcg/dose group had a reduction in their PASI score between baseline and Day 32, and the mean reduction in PASI score was significant in this group (P < 0.01). Dalazatide treatment reduced the plasma levels of multiple inflammation markers and reduced the expression of T cell activation markers on peripheral blood memory T cells. LIMITATIONS The study was small and drug treatment was for a short duration (4 weeks). CONCLUSION This study indicates that dalazatide is generally well tolerated and can improve psoriatic skin lesions by modulating T cell surface and activation marker expression and inhibiting mediators of inflammation in the blood. Larger studies of longer duration are warranted.
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Superior efficacy of calcipotriene and betamethasone dipropionate aerosol foam versus ointment in patients with psoriasis vulgaris--A randomized phase II study.
Koo, J, Tyring, S, Werschler, WP, Bruce, S, Olesen, M, Villumsen, J, Bagel, J
The Journal of dermatological treatment. 2016;(2):120-7
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BACKGROUND An aerosol foam formulation of fixed combination calcipotriene 0.005% (as hydrate; Cal) plus betamethasone dipropionate 0.064% (BD) was developed to improve psoriasis treatment. OBJECTIVES To compare the efficacy and safety of Cal/BD aerosol foam with Cal/BD ointment after 4 weeks. METHODS In this Phase II, multicenter, investigator-blind, 4-week trial, adult patients with psoriasis vulgaris were randomized to Cal/BD aerosol foam, Cal/BD ointment, aerosol foam vehicle or ointment vehicle (3:3:1:1). The primary efficacy endpoint was the proportion of patients at week 4 who achieved treatment success (clear or almost clear with at least a two-step improvement) according to the physician's global assessment of disease severity. RESULTS In total, 376 patients were randomized. At week 4, significantly more patients using Cal/BD aerosol foam achieved treatment success (54.6% versus 43.0% [ointment]; p = 0.025); mean modified (excluding the head, which was not treated) psoriasis area and severity index score was significantly different between Cal/BD aerosol foam and Cal/BD ointment (mean difference -0.6; p = 0.005). Rapid, continuous itch relief occurred with both active treatments. One adverse drug reaction was reported with Cal/BD aerosol foam (application site itch). CONCLUSIONS Cal/BD aerosol foam demonstrates significantly greater efficacy and similar tolerability compared with Cal/BD ointment for psoriasis treatment.
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Cholesterol efflux capacity in humans with psoriasis is inversely related to non-calcified burden of coronary atherosclerosis.
Salahuddin, T, Natarajan, B, Playford, MP, Joshi, AA, Teague, H, Masmoudi, Y, Selwaness, M, Chen, MY, Bluemke, DA, Mehta, NN
European heart journal. 2015;(39):2662-5
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AIMS: Cholesterol efflux capacity (CEC) was recently shown to predict future cardiovascular (CV) events. Psoriasis both increases CV risk and impairs CEC. However, whether having poor CEC is associated with coronary plaque burden is currently unknown. We aimed to assess the cross-sectional relationship between coronary plaque burden assessed by quantitative coronary computed tomography angiography (CCTA) with CEC in a well-phenotyped psoriasis cohort. METHODS AND RESULTS Total burden and non-calcified burden (NCB) plaque indices were assessed in 101 consecutive psoriasis patients using quantitative software. Cholesterol efflux capacity was quantified using a cell-based ex vivo assay measuring the ability of apoB-depleted plasma to mobilize cholesterol from lipid-loaded macrophages. Cholesterol efflux capacity was inversely correlated with NCB (unadjusted β-coefficient -0.33; P < 0.001), and this relationship persisted after adjustment for CV risk factors (β -0.24; P < 0.001), HDL-C levels (β -0.22; P < 0.001), and apoA1 levels (β -0.19; P < 0.001). Finally, we observed a significant gender interaction (P < 0.001) whereby women with low CEC had higher NCB compared to men with low CEC. CONCLUSIONS We show that CEC is inversely associated with prevalent coronary plaque burden measured by quantitative CCTA. Low CEC may therefore be an important biomarker for subclinical coronary atherosclerosis in psoriasis. CLINICALTRIALSGOV NCT01778569.
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Betamethasone valerate dressing is non-inferior to calcipotriol-betamethasone dipropionate ointment in the treatment of patients with mild-to-moderate chronic plaque psoriasis: results of a randomized assessor-blinded multicentre trial.
Ortonne, JP, Esposito, M, Chimenti, S, Kapińska-Mrowiecka, M, Grodzińska, A, Naldi, L, Frangione, V
Journal of the European Academy of Dermatology and Venereology : JEADV. 2014;(9):1226-34
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BACKGROUND A ready-to-use betamethasone valerate 0.1% (BMV) dressing was found to be superior to placebo dressing and a reference 0.1% BMV cream in the treatment of patients with chronic plaque psoriasis (CPP). METHODS This multicentre, prospective, randomized, investigator-blinded, controlled, non-inferiority trial compared the efficacy and safety of the BMV dressing to the calcipotriol-betamethasone dipropionate (CBD) ointment during a 4-week treatment of patients with mild to moderate CPP. The primary efficacy endpoint was the 4-item psoriasis total severity score (TSS-4) at week 4, and the associated non-inferiority margin was 1 point. Secondary outcome measures included the psoriasis global assessment (PGA) score and patients' quality of life (QoL). Safety was assessed through adverse events (AE) reporting in each treatment group. RESULTS Of 325 screened patients, 324 were randomized to BMV (N = 165) or CBD (N = 159), and were considered evaluable for the safety and intention-to-treat (ITT) efficacy analyses. Per protocol (PP) populations included 133 and 131 patients in the BMV and CBD groups respectively. The mean adjusted TSS-4 significantly decreased through the study from baseline in both groups. The PP (primary) analysis of week 4 data revealed a -0.288 (95% CI: -0.610 to 0.034) not significant between-group difference in adjusted means, demonstrating non-inferiority of BMV to CBD. Non-inferiority was also demonstrated in the ITT analysis. The PGA and other secondary outcomes were significantly improved from baseline in both groups at week 4. The QoL score was slightly better in the CBD group at week 4, but no difference was observed at follow-up. No safety or tolerability concerns were observed in either group. CONCLUSIONS BMV dressing is non-inferior to CBD ointment in patients with mild to moderate CPP. Both treatments significantly improve patients' psoriasis and QoL.
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Safety and efficacy of calcipotriol plus betamethasone dipropionate gel in the treatment of scalp psoriasis in adolescents 12-17 years of age.
Gooderham, M, Debarre, JM, Keddy-Grant, J, Xu, Z, Kurvits, M, Goodfield, M
The British journal of dermatology. 2014;(6):1470-7
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BACKGROUND Plaque psoriasis has a relatively high prevalence in adolescence, resulting in a significant impact on quality of life, including social interactions. OBJECTIVES The primary objective was to assess the safety of once-daily application of fixed-combination calcipotriol plus betamethasone dipropionate gel in adolescent scalp psoriasis. Assessment of efficacy was a secondary objective. METHODS This phase II, multicentre, single-arm, open-label, 8-week trial included patients aged 12-17 years with moderate-to-very severe scalp psoriasis according to Investigator's Global Assessment (IGA) (≥ 10% of the scalp area affected). RESULTS Seventy-eight patients received treatment. Twenty-seven patients (35%) reported a total of 64 adverse events (AEs); most were mild (33/64) or moderate (22/64) in severity and there were no serious AEs. No cases of hypercalcaemia were reported, and the mean changes from baseline to end of treatment in albumin-corrected serum calcium (0·00 mmol L(-1)), 24-h urinary calcium excretion (-0·03 mmol per 24 h) and urinary calcium-to-creatinine ratio (-0·12 mmol g(-1)) were not considered clinically relevant. At the end of treatment 66 patients (85%) were clear or almost clear according to IGA. There was an 80% improvement in mean Total Sign Score from baseline to end of treatment. In total, at the end of treatment, 87% of patients rated their scalp psoriasis as clear or very mild, and 75 (96%) had no or mild pruritus compared with 14 (18%) at baseline. CONCLUSIONS Once-daily calcipotriol plus betamethasone dipropionate gel is well tolerated and efficacious for scalp psoriasis in adolescents.