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Efficacy and Safety of a Fixed-Dose Clindamycin Phosphate 1.2%, Benzoyl Peroxide 3.1%, and Adapalene 0.15% Gel for Moderate-to-Severe Acne: A Randomized Phase II Study of the First Triple-Combination Drug.
Stein Gold, L, Baldwin, H, Kircik, LH, Weiss, JS, Pariser, DM, Callender, V, Lain, E, Gold, M, Beer, K, Draelos, Z, et al
American journal of clinical dermatology. 2022;(1):93-104
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BACKGROUND A three-pronged approach to acne treatment-combining an antibiotic, antibacterial, and retinoid-could provide greater efficacy and tolerability than single or dyad treatments, while potentially improving patient compliance and reducing antibiotic resistance. OBJECTIVES We aimed to evaluate the efficacy and safety of triple-combination, fixed-dose topical clindamycin phosphate 1.2%/benzoyl peroxide (BPO) 3.1%/adapalene 0.15% (IDP-126) gel for the treatment of acne. METHODS In a phase II, double-blind, multicenter, randomized, 12-week study, eligible participants aged ≥ 9 years with moderate-to-severe acne were equally randomized to once-daily IDP-126, vehicle, or one of three component dyad gels: BPO/adapalene; clindamycin phosphate/BPO; or clindamycin phosphate/adapalene. Coprimary endpoints were treatment success at week 12 (participants achieving a ≥ 2-grade reduction from baseline in Evaluator's Global Severity Score and clear/almost clear skin) and least-squares mean absolute changes from baseline in inflammatory and noninflammatory lesion counts to week 12. Treatment-emergent adverse events and cutaneous safety/tolerability were also assessed. RESULTS A total of 741 participants were enrolled. At week 12, 52.5% of participants achieved treatment success with IDP-126 vs vehicle (8.1%) and dyads (range 27.8-30.5%; P ≤ 0.001, all). IDP-126 also provided significantly greater absolute reductions in inflammatory (29.9) and noninflammatory (35.5) lesions compared with vehicle or dyads (range inflammatory, 19.6-26.8; noninflammatory, 21.8-30.0; P < 0.05, all), corresponding to > 70% reductions with IDP-126. IDP-126 was well tolerated, with most treatment-emergent adverse events of mild-to-moderate severity. CONCLUSIONS Once-daily treatment with the novel fixed-dose triple-combination clindamycin phosphate 1.2%/BPO 3.1%/adapalene 0.15% gel demonstrated superior efficacy to vehicle and all three dyad component gels, and was well tolerated over 12 weeks in pediatric, adolescent, and adult participants with moderate-to-severe acne. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov identifier NCT03170388 (registered 31 May, 2017).
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Calcipotriol Plus Betamethasone Dipropionate Aerosol Foam in Patients with Moderate-to-Severe Psoriasis: Sub-Group Analysis of the PSO-ABLE Study.
Paul, C, Leonardi, C, Menter, A, Reich, K, Gold, LS, Warren, RB, Møller, A, Lebwohl, M
American journal of clinical dermatology. 2017;(3):405-411
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BACKGROUND Fixed-combination calcipotriol 50 μg/g plus betamethasone 0.5 mg/g (Cal/BD) aerosol foam is a new topical treatment for psoriasis. Although moderate-to-severe psoriasis is typically treated with systemic/biologic therapies, a topical treatment that is efficacious in these patients may be a significant cost-saving alternative to systemic therapy. OBJECTIVE The objective of this study was to assess the response to Cal/BD foam and gel in patients with moderate-to-severe psoriasis enrolled in the phase III, 12-week PSO-ABLE study. METHODS Patients eligible for this analysis had moderate-to-severe psoriasis, defined by the 'Rule of Tens': body surface area ≥10% or Psoriasis Area and Severity Index (PASI) [excluding head; modified PASI (mPASI)] >10 or Dermatology Life-Quality Index >10. Endpoints included: proportion of patients achieving mPASI75 or mPASI90; change in body surface area; proportion of patients clear/almost clear with a ≥2 grade improvement (i.e., treatment success); change in Dermatology Life-Quality Index. RESULTS Seventy-seven Cal/BD foam patients and 82 gel patients had moderate-to-severe psoriasis. A greater proportion achieved mPASI75 and mPASI90 with Cal/BD foam than gel at weeks 4, 8, and 12 (57.1 vs. 35.4%; p = 0.006 and 15.6 vs. 12.2% at week 12, respectively); overall reduction in mPASI from baseline to week 12 was 64% with the foam vs. 51% with the gel. Overall reduction in body surface area at week 12 was 50% with the foam and 39% with the gel. Treatment success rates were higher with the Cal/BD foam than the gel at weeks 1, 2, 4, 8 (p = 0.0089), and 12, and a greater proportion of foam patients achieved a Dermatology Life-Quality Index score of 0/1 at weeks 4 (p = 0.004), 8, and 12 (p = 0.001). CONCLUSION Cal/BD foam can be considered as a treatment option in some patients with moderate-to-severe psoriasis who are potential candidates for systemic therapy. CLINICALTRIALS. GOV IDENTIFIER NCT02132936.
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Double-blind, randomized phase 3 trial of low-dose 13-cis retinoic acid in the prevention of second primaries in head and neck cancer: Long-term follow-up of a trial of the Eastern Cooperative Oncology Group-ACRIN Cancer Research Group (C0590).
Bhatia, AK, Lee, JW, Pinto, HA, Jacobs, CD, Limburg, PJ, Rubin, P, Arusell, RM, Dunphy, EP, Khandekar, JD, Reiner, SA, et al
Cancer. 2017;(23):4653-4662
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BACKGROUND 13-Cis retinoic acid (13-CRA) is a synthetic vitamin A derivative. High-dose 13-CRA in patients with squamous cell cancers of the head and neck (SCCHNs) reduces the incidence of second primary tumors (SPTs). The authors report long-term results from a phase 3 randomized trial that compared treatment with low-dose 13-CRA versus placebo for patients who had early stage SCCHN, with a focus on the development of SPTs and overall survival (OS). METHODS In total, 176 patients who received treatment for stage I/II SCCHN were randomized to receive either low-dose 13-CRA (weight-based dose of 7.5 mg or 10 mg) or placebo for 2 years. A competing-risk approach and the log-rank test were used to compare the time to SPT and OS, respectively, between groups. RESULTS 13-CRA neither significantly reduced the cumulative incidence of SPT (P = .61) nor improved the time to SPT (hazard ratio [HR] for 13-CRA/placebo; 0.86; P = .61). Despite limited power, there was a trend toward improved OS for the 13-CRA arm (HR, 0.75; P = .14), particularly among patients whose index tumor was surgically excised (N = 26; HR, 0.50; P = .057) and among women (N = 39; HR, 0.44; P = .065) and never/former smokers (N = 129; HR, 0.61; P = .055), with a median follow-up of 16 years. The main 13-CRA related toxicities were dry skin and cheilitis. CONCLUSIONS Treatment with low-dose 13-CRA for 2 years did not decrease the incidence of SPT; subset analysis indicates a potential survival advantage among patients who are women and never/former smokers. More targeted interventions based on clinical risk factors and molecular characterization of tumors may yield greater success in future prevention trials. Cancer 2017;123:4653-4662. © 2017 American Cancer Society.
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Efficacy of a fixed combination of calcipotriol/betamethasone dipropionate topical gel in adult patients with mild to moderate psoriasis: blinded interim analysis of a phase IV, multicenter, randomized, controlled, prospective study.
Reich, K, Zschocke, I, Bachelez, H, de Jong, EM, Gisondi, P, Puig, L, Warren, RB, Mrowietz, U, ,
Journal of the European Academy of Dermatology and Venereology : JEADV. 2015;(6):1156-63
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BACKGROUND Psoriasis is a common, chronic, inflammatory skin disease with the majority of individuals having limited disease, treated with topical medication. However, special attributes of topical treatments like galenic/cosmetic properties or an inconvenient treatment schedule may result in low preference for topical treatments. Hence, there is strong medical need for a topical medication, which is highly efficacious, easy-to-use and preferred by both physicians and patients. OBJECTIVE Blinded interim analysis with the purpose to assess efficacy of (both from the physician's and patient's perspective) and the patients' preference with a highly efficacious and easy-to-use fixed combination of calcipotriol/betamethasone dipropionate topical gel after 8 weeks of once daily treatment in a large patient population. METHODS In this phase IV, international, multicentre, randomized, controlled, prospective, parallel group study, adult patients with active, mild to moderate psoriasis despite previous topical psoriasis treatment, i.e. unsuccessful in the 8 weeks preceding study participation, are followed over 64 weeks. During the first 8 weeks the patients apply their medication once a day followed by a 56-weeks maintenance period according to SmPC. Blinded interim analysis of all patients included demographics, Physician's Global Assessment, the novel Patient's self Global Assessment (PsGA) and Patient Preference Questionnaire (PPQ). RESULTS 1795 patients were analysed. At week 8, 36.5% of the physicians rated the patients' psoriasis as clear/almost clear. Similarly, based on the patients' self-assessment, 34.2% had a clear/almost clear score of PsGA in week 8. Analysis of the PPQ showed that the vast majority of the patients judged their 8-week treatment to be preferable compared with their previous treatments. CONCLUSION Results of this blinded interim analysis indicate that the fixed combination of calcipotriol/betamethasone dipropionate gel is highly efficacious and preferred by the majority of analysed patients.
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The Vitamin D Analogue Calcipotriol Reduces the Frequency of CD8+ IL-17+ T Cells in Psoriasis Lesions.
Dyring-Andersen, B, Bonefeld, CM, Bzorek, M, Løvendorf, MB, Lauritsen, JP, Skov, L, Geisler, C
Scandinavian journal of immunology. 2015;(1):84-91
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The vitamin D analogue calcipotriol is an immunomodulatory drug widely used to treat psoriasis; however, how calcipotriol affects the immune cells in psoriasis lesions is not fully understood. The aim of this study was to investigate the effect of calcipotriol on the frequency of CD4(+) and CD8(+) T cells and innate lymphoid cells (ILC) and their production of IL-17A, IFN-γ and IL-22 in psoriasis lesions in patients with chronic plaque psoriasis. Eighteen patients with psoriasis were included, and two similar psoriasis lesions were chosen for each patient. One lesion was treated with calcipotriol (50 μg/g) and the other with vehicle twice a day for 14 days. The clinical effect was measured by degree of erythema, scaling and induration in each lesion (SUM score). Skin biopsies were collected for histological and immunohistochemical analyses. Skin-derived cells were isolated and analysed by flow cytometry. After 14 days of treatment with calcipotriol, a significant clinical and histological effect was seen; however, we found no differences in the frequency of CD4(+) and CD8(+) T cells or ILC between calcipotriol- and vehicle-treated skin. The main finding was a significant decrease in CD8(+) IL-17(+) T cells in skin-derived cells from calcipotriol-treated skin, which was further supported by the absence of CD8(+) IL-17(+) T cells in immunohistochemical staining of calcipotriol-treated skin. No changes in the frequency of IL-22(+) or IFN-γ(+) cells were observed. Our findings show that the vitamin D analogue calcipotriol reduces the frequency of CD8(+) IL-17(+) T cells in psoriasis lesions concomitant with clinical improvement.
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Safety and efficacy of calcipotriene plus betamethasone dipropionate topical suspension in the treatment of extensive scalp psoriasis in adolescents ages 12 to 17 years.
Eichenfield, LF, Ganslandt, C, Kurvits, M, Schlessinger, J
Pediatric dermatology. 2015;(1):28-35
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The objective of this study was to assess the safety and efficacy of the fixed combination calcipotriene 0.005% plus betamethasone dipropionate 0.064% topical suspension in adolescents with extensive scalp psoriasis. In this phase II, open-label, 8-week study, adolescents with psoriasis (ages 12-17 years) with 20% or more of the scalp area affected (at least moderate severity according to Investigator's Global Assessment [IGA]) were assigned to once-daily treatment with calcipotriene plus betamethasone dipropionate topical suspension. The primary endpoint was safety, focusing on calcium metabolism and hypothalamic-pituitary-adrenal axis function. Secondary efficacy endpoints were the proportion of patient's achieving treatment success (clear or almost clear disease according to the IGA and clear or very mild disease according to the Patient's Global Assessment [PaGA]) and percentage change in investigator-assessed Total Sign Score (TSS). Pruritus was also assessed. Overall, 31 patients received treatment. Sixteen patients (52%) experienced a total of 20 adverse events; 19 were considered unrelated to study treatment, 14 were mild, and none were serious or lesional or perilesional on the scalp. One patient showed signs of mild adrenal suppression at week 4; the patient discontinued treatment and had normal test results at follow-up 4 weeks later. No cases of hypercalcemia were reported. By treatment end, treatment success was reported for 17 patients (55%) according to the IGA and 18 (58%) according to the PGA. Mean TSS improved from 6.9 at baseline to 2.9 at treatment end (59% improvement). By week 8, 28 patients (90%) experienced mild or no itching, versus 20 (65%) at baseline. Once-daily calcipotriene plus betamethasone dipropionate topical suspension was well tolerated and efficacious for the treatment of scalp psoriasis in adolescents.
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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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Topical treatment of actinic keratoses with potassium dobesilate 5% cream. a preliminary open-label study.
Cuevas Sánchez, P, Espinoza, W, Pérez, C, Angulo, J, Giménez-Gallego, G
European journal of medical research. 2011;(2):67-70
Abstract
BACKGROUND Fibroblast growth factor (FGF) is involved in skin tumorigenesis: it promotes cell viability, induces angiogenesis and stimulates invasiveness. Dobesilate is a drug that blocks the activity of FGF. The primary objective was to evaluate the efficacy and tolerability of potassium dobesilate 5% cream in the treatment of actinic keratoses. METHODS Potassium dobesilate 5% cream was applied twice daily for 16 weeks to actinic keratosis lesions in 30 patients. The lesions were evaluated clinically at an initial baseline visit, at intermediate visits, and at 16 weeks of treatment. - RESULTS The use of potassium dobesilate 5% cream for 16 weeks induced complete regression in 70% of evaluated actinic keratoses, corresponding to grade I, II and III clinical variants, and a partial response (at least 75% reduction of lesions) in 20% of the cases. CONCLUSION Our preliminary trial shows that potassium dobesilate exerts anti-tumorigenic effects and may play a useful role in the chemoprevention of skin cancers.
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Dovobet ointment under occlusion overnight for troublesome scalp psoriasis.
Downs, AM
Acta dermato-venereologica. 2006;(1):57-8
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Combination therapy with adapalene gel 0.1% and doxycycline for severe acne vulgaris: a multicenter, investigator-blind, randomized, controlled study.
Thiboutot, DM, Shalita, AR, Yamauchi, PS, Dawson, C, Arsonnaud, S, Kang, S, ,
Skinmed. 2005;(3):138-46
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BACKGROUND Combination therapy with a topical retinoid and an antibiotic is recognized as a rational and effective approach for the treatment of acne vulgaris. Adapalene, a naphthoic acid derivative with anti-inflammatory and receptor-selective retinoid properties, is safe and well tolerated. While the combination of adapalene with oral or topical antibiotics has been shown to deliver a superior and faster response than an antibiotic alone, the clinical benefits of a combination of adapalene and doxycycline, the most frequently prescribed oral antibiotic for acne in the United States, have yet to be evaluated. OBJECTIVE AND METHODS In a 12-week study, the efficacy and safety of the combination of adapalene gel 0.1% with doxycycline was compared with doxycycline alone for the treatment of severe acne. Subjects were randomized to receive doxycycline once daily in the morning and either adapalene or vehicle once daily in the evening. RESULTS At Week 12, the combination adapalene-doxycycline was significantly superior to doxycycline alone for change from baseline in total (p<0.001), inflammatory (p=0.02), and noninflammatory (p<0.001) lesions. Significant differences in total lesions were observed as early as Week 4 (p=0.04). Both treatments were well tolerated, and no serious adverse events were reported. CONCLUSIONS The study demonstrates that the combination of adapalene and an oral antibiotic provides a superior and faster benefit than antibiotic therapy alone and should be considered at the initiation of treatment.