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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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Abstract
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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Efficacy and safety of HAT1 compared with calcipotriol in the treatment of patients with mild to moderate chronic plaque psoriasis: results from an open-label randomized comparative pilot clinical study.
Alex, P, Williams, S, Sutton, L, Yesudas, T, Sutton, C, Thomas, S, Centola, M
Clinical and experimental dermatology. 2020;(3):318-322
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Abstract
Psoriasis is commonly treated with topical corticosteroids, oral cytotoxic drugs and biologic agents, which can be associated with significant adverse effects (AEs), high cost and response attenuation. Additionally, patients often use alternative therapies ad hoc, which can be challenging to integrate into a treatment regimen, owing to a lack of adequately powered controlled trials assessing efficacy and safety. We developed a novel topical botanical complex, herbal anti-inflammatory treatment (HAT1), through extensive preclinical in vitro and in vivo modelling to define key mechanisms of action and clinical potential. To assess the efficacy and safety of HAT1 in psoriasis, we performed a 10-week, open-label, pilot clinical trial comparing topical treatment of HAT1 with calcipotriol 0.005% in adult patients with mild to moderate psoriasis. Primary and secondary endpoints included the percentage of patients obtaining improvement of ≥ 75% in Psoriasis Area and Severity Index (PASI 75), Physician's Global Assessment (PGA) response, and evaluation of tolerability and safety of HAT1. In the HAT1 arm, 85.7% of study patients reached PASI 75 compared with 21.4% in the calcipotriol comparator group. Additionally, 78.6% of patients in the HAT1 arm achieved a 'clear' or 'minimal' PGA response. HAT1 was well tolerated, with no AEs observed throughout the trial. These results suggest that HAT1 reduces psoriasis disease activity in a clinically relevant manner. Ongoing studies, including well-powered, double-blind, randomized controlled trials will be required to assess the potential of HAT1 in psoriasis.
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Effect of Calcipotriene/Betamethasone Dipropionate 0.005%/0.064% Foam on Target Lesions in Plaque Psoriasis: A Post-Hoc Analysis.
Veverka, KA, Patel, DS, Anger, T, Hansen, B, Del Rosso, J, Kircik, LH
Journal of drugs in dermatology : JDD. 2020;(2):121-126
Abstract
Objective: Investigate the effect of fixed-combination calcipotriene 0.005% plus betamethasone dipropionate 0.064% (Cal/BD) foam on target lesion severity in plaque psoriasis. Design: Post-hoc analysis was conducted on data from a Phase 3, randomized, double-blind, multicenter clinical study of Cal/BD foam in the treatment of psoriasis vulgaris for 4 weeks (PSO-FAST; NCT01866163). Participants: In PSO-FAST, 426 patients (≥18 years) with psoriasis vulgaris (≥mild severity) were randomized 3:1 to Cal/BD foam (n=323) or vehicle foam (n=103), applied once daily. Measurements: Assessments included (1) target lesion severity (redness, scaliness, and thickness) at baseline and weeks 1, 2, and 4; and (2) the proportion of patients with ≥50% reduction in total sign score (TSS-50) from baseline at weeks 1, 2, and 4. Results: A greater proportion of patients achieved considerable improvement (a score of 0 or 1) in the severity of target lesions after 4 weeks of treatment with Cal/BD foam vs vehicle foam at week 4 (redness: 76.2% vs 21.4%; P<.001; scaliness: 91.3% vs 61.2%; P<.001; and thickness: 83.3% vs 35.0%; P<.001, respectively). Rapid onset of efficacy was observed as early as week 1. Significantly more patients also achieved TSS-50 at week 4 with Cal/BD foam vs vehicle foam for their target lesions regardless of treatment area, including the elbows and knees (P<.05 for all). Conclusions: Significant improvements in target lesion severity were achieved with up to 4 weeks of treatment with once-daily Cal/BD foam for adults with plaque psoriasis versus vehicle foam, with rapid onset of efficacy observed at week 1. J Drugs Dermatol. 2020;19(2)121-126. doi:10.36849/JDD.2020.4750
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Iontophoretic delivery of methotrexate in the treatment of palmar psoriasis: A randomised controlled study.
Andanooru Chandrappa, NK, Channakeshavaiah Ravikumar, B, Rangegowda, SM
The Australasian journal of dermatology. 2020;(2):140-146
Abstract
BACKGROUND/OBJECTIVES Palmoplantar psoriasis is a localised variant of psoriasis. Topical therapy is the preferred treatment modality, but in severe and recalcitrant cases, systemic drugs like methotrexate are prescribed, with potential for significant adverse effects. Iontophoresis is gaining popularity in enhancing the transdermal delivery of drugs in ionic state. This study was undertaken to evaluate and compare the efficacy of topical methotrexate by iontophoresis technique with clobetasol propionate 0.05% ointment in the treatment of palmar psoriasis. METHODS This was a prospective randomised controlled study conducted on patients with palmar psoriasis. Group 1 patients (n = 31) were treated with once weekly iontophoretic delivery of methotrexate over 6 sittings, and group 2 patients (n = 31) were treated with clobetasol propionate 0.05% ointment, twice daily for 6 weeks. Severity of palmar psoriasis was assessed by modified Palmoplantar Pustular Psoriasis Area and Severity Index (m-PPPASI), and treatment was considered as satisfactory when there was >50% improvement. RESULTS Sixty two patients were recruited, of which 50 completed the study. Eight out of 25 (32%) patients in group 1 and 12 out of 25 (48%) patients in group 2 showed satisfactory improvement at the end of 6 weeks. However, this difference was statistically not significant (P = 0.25). Burn injury was noted in 12 (48%) group 1 patients with no adverse effects in group 2. CONCLUSION Iontophoretic delivery of methotrexate is a promising therapeutic modality, the efficacy of which is comparable to that of clobetasol propionate ointment in the treatment of palmar psoriasis.
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Vasoconstrictor potency of fixed-dose combination calcipotriol (50 μg/g) and betamethasone dipropionate (0.5 mg/g) cutaneous foam versus other topical corticosteroids used to treat psoriasis vulgaris.
Queille-Roussel, C, Nielsen, J, Lacour, JP
The Journal of dermatological treatment. 2019;(6):529-533
Abstract
Background: It is important to determine the vasoconstrictor potencies of topical corticosteroids used to treat psoriasis to ensure appropriate clinical use. Objective: To compare the vasoconstrictive potencies of fixed-dose combination calcipotriol (50 μg/g) and betamethasone dipropionate (0.5 mg/g) (Cal/BD) cutaneous foam with other topical corticosteroids. Methods: In this Phase I, single-center, healthy volunteer study, Cal/BD foam, clobetasol propionate 0.05% cream (CP; very potent), BD 0.05% ointment (potent), mometasone furoate 0.1% cream (MF; potent), hydrocortisone-17-butyrate 0.1% ointment (HB; moderately potent), and foam vehicle were applied, then removed after 16 h. Skin blanching was visually assessed 2 h later (scale of 0-4). Results: Thirty-six volunteers were randomized. Skin blanching with Cal/BD foam (median [range], 2.00 [0.75-3.00]) was significantly lower than CP cream (3.00 [1.75-4.00]; p < .001), was not significantly different from BD ointment (1.75 [0.75-3.00]; p = .30) and MF cream (2.00 [1.00-3.75]; p = .22), and was significantly greater than HB ointment (1.25 [0.50-3.00]; p < .001) and vehicle (0 [0-0.50]; p < .001). There were no local tolerability reactions or adverse events. Conclusions: The corticosteroid potency of Cal/BD foam was not significantly different from BD ointment and MF cream, significantly stronger than HB ointment, but weaker than CP cream in healthy volunteers.
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Discovery of increased epidermal DNAH10 expression after regeneration of dermis in a randomized with-in person trial - reflections on psoriatic inflammation.
Lagus, H, Klaas, M, Juteau, S, Elomaa, O, Kere, J, Vuola, J, Jaks, V, Kankuri, E
Scientific reports. 2019;(1):19136
Abstract
Because molecular memories of past inflammatory events can persist in epidermal cells, we evaluated the long-term epidermal protein expression landscapes after dermal regeneration and in psoriatic inflammation. We first characterized the effects of two dermal regeneration strategies on transplants of indicator split-thickness skin grafts (STSGs) in ten adult patients with deep burns covering more than 20% of their body surface area. After fascial excision, three adjacent areas within the wound were randomized to receive a permanent dermal matrix, a temporary granulation-tissue-inducing dressing or no dermal component as control. Control areas were covered with STSG immediately, and treated areas after two-weeks of dermis formation. Epidermis-dermis-targeted proteomics of one-year-follow-up samples were performed for protein expression profiling. Epidermal expression of axonemal dynein heavy chain 10 (DNAH10) was increased 20-fold in samples having had regenerating dermis vs control. Given the dermal inflammatory component found in our dermal regeneration samples as well as in early psoriatic lesions, we hypothesized that DNAH10 protein expression also would be affected in psoriatic skin samples. We discovered increased DNAH10 expression in inflammatory lesions when compared to unaffected skin. Our results associate DNAH10 expression with cell proliferation and inflammation as well as with the epidermal memory resulting from the previous regenerative signals of dermis. This study (ISRCTN14499986) was funded by the Finnish Ministry of Defense and by government subsidies for medical research.
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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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Abstract
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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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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Efficacy, safety, and cost-effectiveness of all-trans retinoic acid/Clobetasol Propionate Compound Ointment in the treatment of mild to moderate psoriasis vulgaris: A randomized, single-blind, multicenter clinical trial.
Xia, L, Li, R, Wang, Y, Lin, Z, Zheng, J, Li, X, Lu, Q, Zhang, J, Jin, H, Fu, L, et al
Dermatologic therapy. 2018;(5):e12632
Abstract
To assess the efficacy, safety, and cost-effectiveness of all-trans retinoic acid/Clobetasol Propionate Compound Ointment and calcipotriol/betamethasone dipropionate ointment in the treatment of mild-to-moderate patients with psoriasis vulgaris. This was a randomized, single-blind, multicenter clinical trial. A total of 240 patients were randomized to receive twice-daily all-trans retinoic acid/Clobetasol Propionate Compound Ointment (treatment group) or once-daily calcipotriol/betamethasone dipropionate ointment (control group) for 4 weeks. The efficacy, safety, and cost-effectiveness were assessed at Weeks 2 and 4. After 4 weeks, both groups showed a significant clinical improvement compared to baseline (88.33% vs. 89.83%, respectively, p = .7112). But PASI 75 response in the treatment group was superior to the control group (44.12% vs. 28.57%, respectively, p = .0200), at Week 4. SSRI improvement rate in the treatment group was also superior to control group (67.11% vs. 59.43%, respectively, p = .0119) at Week 4. All-trans retinoic acid/Clobetasol Propionate Compound Ointment showed a significant clinical improvement in erythema, infiltration, and scales of skin lesions and PASI score compared to baseline. 1.67% of patients (treatment group) reported adverse reactions compared to 2.50% (control group) with no statistical significance. In addition, the cost-effectiveness assessment showed a higher cost-effectiveness of the treatment group compared to the control group in 4 weeks (199.25 vs. 801.51). All-trans retinoic acid/Clobetasol Propionate Compound Ointment was effective and safe in the treatment of psoriasis vulgaris with similar efficacy as calcipotriol/betamethasone dipropionate ointment and lower treatment costs.
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Safety of Adalimumab in Pediatric Patients with Polyarticular Juvenile Idiopathic Arthritis, Enthesitis-Related Arthritis, Psoriasis, and Crohn's Disease.
Horneff, G, Seyger, MMB, Arikan, D, Kalabic, J, Anderson, JK, Lazar, A, Williams, DA, Wang, C, Tarzynski-Potempa, R, Hyams, JS
The Journal of pediatrics. 2018;:166-175.e3
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Abstract
OBJECTIVE To evaluate the safety of adalimumab in pediatric patients who participated in clinical trials of juvenile idiopathic arthritis (polyarticular juvenile idiopathic arthritis and pediatric enthesitis-related arthritis), psoriasis, and Crohn's disease. STUDY DESIGN This analysis included data from 7 global, randomized, and open-label AbbVie-sponsored clinical trials of adalimumab and their open-label extensions conducted between September 2002 and December 31, 2015 (cutoff date for ongoing studies). Patients who received ≥1 dose of adalimumab subcutaneously were included. Adverse events that occurred after the first dose of adalimumab and up to 70 days (5 half-lives) after the last dose were reported and events per 100 patient-years were calculated. RESULTS The analysis included 577 pediatric patients, representing 1440.7 patient-years of adalimumab exposure. Across indications, the most commonly reported adverse events (events/100 patient-years) were upper respiratory tract infections (24.3), nasopharyngitis (17.3), and headache (19.9). Serious infections (4.0 events/100 patient-years) were the most frequent serious adverse events across indications; the most commonly reported was pneumonia (0.6 events/100 patient-years). Serious infection rates were 2.7, 0.8, and 6.6 events/100 patient-years in patients with juvenile idiopathic arthritis, psoriasis, and Crohn's disease, respectively. No events of malignancies were reported. One death (accidental fall) occurred in a patient with psoriasis. CONCLUSIONS The safety profile of adalimumab in pediatric patients with polyarticular juvenile idiopathic arthritis, enthesitis-related arthritis, psoriasis, and Crohn's disease was generally similar across indications; no new safety signals were identified in the treatment of pediatric patients with adalimumab. TRIAL REGISTRATION Clinicaltrials.gov: NCT00048542, NCT00775437, NCT00690573, NCT01166282, NCT01251614, NCT00409682, and NCT00686374.