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The combined treatment with calcipotriol (Cal) and betamethasone dipropionate (BDP) has emerged as the leading anti-psoriatic topical treatment. Fixed-dose Cal/BDP is available in different formulations, including ointment, gel, foam, and cream. This review examines the mechanism of action of Cal/BDP underlying its therapeutic effect and compiles the evidence regarding its efficacy and safety compared to monotherapy with topical corticosteroids. The dual-action of Cal/BDP targets the inflammatory pathways and abnormal keratinocyte proliferation, both of them fundamental mechanisms of psoriasis pathogenesis. A large number of randomized, double-blind studies support Cal/BDP superiority over topical corticosteroids, demonstrating its broad efficacy across several degrees of psoriasis severity and its capability to provide early significant clinical improvements. This increased efficacy is achieved without negative effects on the safety profile, since the incidence of adverse effects reported with Cal/BDP is usually similar to that of BDP and even lower than that of Cal alone. The combination therapy rapid onset of action, coupled with a simplified dosing regimen, has been identified as crucial for improving long-term adherence and patient outcomes. In conclusion, Cal/BDP is confirmed as a versatile, effective, and convenient option for the patient in psoriasis management. [ABSTRACT FROM AUTHOR]

Background/Objectives: Actinic keratoses (AK) are premalignant skin lesions caused by chronic sun exposure, topically managed by 5-fluorouracil (5-FU), diclofenac 3% gel, and imiquimod. Despite their effectiveness, long treatment duration and severe adverse local skin reactions have limited patient concordance. Calcipotriol has recently been used as a combination agent for existing topical AK treatments. A systematic review was performed to determine the clinical efficacy of 5-FU and calcipotriol for the treatment of AK, Bowen's disease, and squamous cell carcinoma (SCC). Methods: A systematic literature search was conducted on Medline, Embase, and Cochrane Library. Among the 84 records screened, 12 were retrieved for full-text review and 8 were included in the final analysis. Results: Among the 8 studies, there were 214 control patients and 288 patients who received the intervention. The combination 5% 5-FU with calcipotriol resulted in a significant reduction in the number of AKs on the face, scalp, right upper extremity, and left upper extremity for all sites at 8 weeks (P <.0001). No significant difference in SCC incidence was observed at 1 or 2 years, but there was a significant reduction observed at 3 years for SCC on face and scalp. No study assessed the combination for Bowen's disease. Conclusions: Combination 5% 5-FU with calcipotriol is an effective treatment for Aks; however, future trials may consider longer treatment and follow-up periods for the treatment and prevention of AK, SCC in situ, and SCC. [ABSTRACT FROM AUTHOR]

Small plaque psoriasis is the typical form of chronic plaque psoriasis affecting adults in South Korea. The effectiveness of calcipotriol/betamethasone dipropionate (Cal/BD) aerosol foam for large and small psoriasis plaques has not previously been examined. We performed a post hoc analysis of a recent, 4‐week observational study of Cal/BD aerosol foam use in routine clinical practice in South Korea. Investigator Global Assessment response ([IGA] 0/1 at week 4), Patient Global Assessment response ([PaGA] 0/1 at week 4), change in Psoriasis Area and Severity Index (PASI), changes in psoriasis symptom scores, change in the Dermatology Life Quality Index (DLQI), and the proportion of patients achieving DLQI ≤5 were analyzed for patients with small (≤5 cm; n = 131) or large (>5 cm; n = 35) baseline plaque size. IGA response rates were similar for patients with small and large plaques (59.5% and 51.4% respectively). Similarly, there was no significant difference between the small and large groups in mean change in PASI (−2.20 vs −3.34), the proportions of patients with DLQI ≤5 (62.3% vs 54.3%) or PaGA 0/1 (29.2% vs 40.0%). Mean improvements in DLQI (−4.04 vs −6.20) and in psoriasis symptoms including itching (−1.50 vs −2.83), sleep loss (−0.67 vs −1.89), dryness (−1.57 vs −2.97), scaling (−1.21 vs −3.57), and redness (−1.17 vs −3.11) were greater in patients with large plaques than those with small plaques. Itching and DLQI differences were not statistically significant after adjustment for baseline characteristics. Stratification by body surface area affected eliminated statistically significant differences between the groups for most outcomes. In conclusion, this analysis suggests that Cal/BD aerosol foam is an effective, well‐accepted treatment for adult patients with the small plaques typical of chronic plaque psoriasis in South Korea, as well as for those with large plaques. [ABSTRACT FROM AUTHOR]

Excessive exposure to ultraviolet (UV) radiation causes premature aging of the skin, known as photoaging. UV radiation induces DNA damage, oxidative stress, inflammatory reactions, and degradation of extracellular matrix (ECM) proteins, contributing to the aged skin phenotype. The skin synthesizes vitamin D upon UVB exposure, which plays a pivotal role in the proper function of multiple body systems. Vitamin D protects skin from photo-damage by repairing cyclobutane pyrimidine dimers, reversing oxidative stress, and reducing chronic inflammation. Moreover, various epidemiological studies have identified vitamin D deficiency as a marker for common dermatological disorders. Improvement of clinical outcomes with vitamin D supplementation further suggests its protective role against skin pathologies. This review comprehensively covers the involvement of vitamin D in combating UV-induced photoaging and various skin disorders, highlighting the significance of maintaining vitamin D adequacy for healthy skin.

The scalp is the most common site affected in patients with psoriasis with up to 80% of these patients having some degree of scalp involvement. In this narrative review, we evaluate available data on the use of an innovative aerosol foam formulation of calcipotriol plus betamethasone dipropionate (Cal/BD) to treat patients with psoriasis and scalp involvement. The full PubMed database was searched using the terms “calcipotriol”, “betamethasone dipropionate” and “aerosol foam”, and all articles relating to “psoriasis with scalp involvement” were retrieved and used in the preparation of this review. The evidence supporting the clinical effectiveness, tolerability and impact on health outcomes of Cal/BD aerosol foam in patients with scalp psoriasis was obtained from a phase II clinical trial and real-world evidence data from a non-interventional study as well as from two case series. The findings from these studies show that Cal/BD aerosol foam is rapidly effective, improves skin condition, alleviates symptoms such as itch, and has a positive impact on patient quality of life. These attributes address several unmet needs for patients with psoriasis with scalp involvement and have the potential to improve individual adherence to treatment.

AbstractObjectiveMethodsResultsConclusionTo observe the clinical efficacy of calcipotriol combined with AYJ(An Yi Jia) sodium alginate repair dressing in the treatment of psoriasis vulgaris (PV) and its effect on patients’ neurological function.A retrospective analysis was conducted on the clinical data of 103 patients with PV admitted to our hospital from January 2022 to January 2024. All patients met the inclusion and exclusion criteria. According to the treatment interventions received by the patients, they were divided into control group (n = 51, receiving calcipotriol monotherapy) and observation group (n = 52, receiving calcipotriol combined with AYJ sodium alginate repair dressing). The clinical treatment effects, severity of the disease (PSSI score), levels of T lymphocyte subsets (CD4+, CD8+), serum nerve growth factor (NGF), inflammatory factors [interferon-gamma (IFN-γ), interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-α)], and adverse reactions were compared between the two groups.① Clinical treatment effects: The total effective rate in the observation group was higher than that in the control group (p < 0.05). ② Severity of the disease: The PASI scores of both groups gradually decreased with prolonged treatment time, and the observation group showed a greater magnitude of change (p < 0.05). ③ T lymphocyte subset cells and serum nerve growth factor: The levels of CD4+ were increased after treatment in both groups, while CD8+ and NGF levels were decreased compared to before treatment, with a greater magnitude of change in the observation group (p < 0.05). ④ Inflammatory factors: The levels of IFN-γ, IL-8, and TNF-α were decreased after treatment in both groups, with a greater magnitude of change in the observation group (p < 0.05). ⑤ Adverse reactions: There was no significant difference in the incidence of adverse reactions between the two groups (p > 0.05).Calcipotriol combined with AYJ sodium alginate repair dressing has ideal therapeutic effects in the treatment of PV. Compared with calcipotriol alone, the combined application of AYJ sodium alginate repair dressing can further improve patient efficacy, improve immune and neurological function, alleviate patient inflammatory responses, and does not increase the risk of adverse reactions in patients. [ABSTRACT FROM AUTHOR]

Calcipotriol (calcipotriene) is a synthetic vitamin D3 derivative that is a standard treatment option for psoriasis. It is generally well tolerated with minimal side effects. Due to its ability to reduce keratinocyte proliferation and induce keratinocyte differentiation as well as its immunomodulatory effects, calcipotriol has been used to treat a variety of skin disorders such as atopic dermatitis, actinic keratoses, lichen planus, seborrheic keratoses, and vitiligo [1]. We surveyed the literature examining the use of calcipotriol for non-psoriatic dermatologic disease.

Abstract Introduction Plaque psoriasis is a chronic relapsing inflammatory skin disease that is associated with extensive disease burden that often requires long-term therapy. Treatment of psoriasis with 4 weeks of the aerosol foam formulation of calcipotriol/betamethasone dipropionate (Cal/BD; Enstilar®, LEO Pharma) has been demonstrated to be effective, well tolerated, and associated with high patient satisfaction. Cal/BD foam is approved as a first-line treatment in multiple countries, where several non-interventional studies (NIS) have corroborated the beneficial efficacy and safety profiles determined in the randomized clinical trials. Heterogenicity in these NIS, however, prevents the use of a data pooling strategy for comparisons of effectiveness outcomes across different patient populations. Methods Therefore, here, we report on a post hoc analysis of effectiveness data consolidated from six prospective NIS to discern any differences in improvement in signs and symptoms of psoriasis attributable to Cal/BD foam treatment across the countries. In addition, we provide real-world experience of clinicians with Cal/BD foam treatment, factoring in changes in usage since these NIS were performed in their local markets. Results This post hoc analysis of Cal/BD foam NIS brings together data outside of randomized clinical trials from six countries to provide real-world evidence in 1388 patients showing that 4 weeks of Cal/BD foam is an effective and safe treatment option with quick onset of action for patients with psoriasis. Conclusion These results show that regardless of NIS location, Cal/BD foam remains a well-tolerated, efficacious option for patient care that could be used as a first-line topical therapy for mild-to-severe psoriasis.

Introduction: Plaque psoriasis is a chronic relapsing inflammatory skin disease that is associated with extensive disease burden that often requires long-term therapy. Treatment of psoriasis with 4 weeks of the aerosol foam formulation of calcipotriol/betamethasone dipropionate (Cal/BD; Enstilar®, LEO Pharma) has been demonstrated to be effective, well tolerated, and associated with high patient satisfaction. Cal/BD foam is approved as a first-line treatment in multiple countries, where several non-interventional studies (NIS) have corroborated the beneficial efficacy and safety profiles determined in the randomized clinical trials. Heterogenicity in these NIS, however, prevents the use of a data pooling strategy for comparisons of effectiveness outcomes across different patient populations. Methods: Therefore, here, we report on a post hoc analysis of effectiveness data consolidated from six prospective NIS to discern any differences in improvement in signs and symptoms of psoriasis attributable to Cal/BD foam treatment across the countries. In addition, we provide real-world experience of clinicians with Cal/BD foam treatment, factoring in changes in usage since these NIS were performed in their local markets. Results: This post hoc analysis of Cal/BD foam NIS brings together data outside of randomized clinical trials from six countries to provide real-world evidence in 1388 patients showing that 4 weeks of Cal/BD foam is an effective and safe treatment option with quick onset of action for patients with psoriasis. Conclusion: These results show that regardless of NIS location, Cal/BD foam remains a well-tolerated, efficacious option for patient care that could be used as a first-line topical therapy for mild-to-severe psoriasis. [ABSTRACT FROM AUTHOR]

Tapinarof is an aromatic hydrocarbon receptor inhibitor for the treatment of adult psoriasis, and with the completion of Phase III clinical trials for this drug, it is important to understand its place among the medications used in the treatment of psoriasis for clinical application. Networks were constructed for 1% tapinarof cream with positive control (calcipotriol) and negative control (placebo). Network meta-analysis was performed using Preferred Reporting Items for Systematic Reviews and Meta-analyses (PISMA) 2015. Relevant randomized clinical trials were searched from PubMed, Cochrane Library, and National Knowledge Infrastructure (CNKI) as of February 2023. Data were analyzed using the gemtc package in R software (RStudio) to evaluate the efficacy and safety of 1% tapinarof cream in the treatment of psoriasis in adults. A total of 2408 patients were enrolled in 8 clinical studies of 1% tapinarof cream, and 6874 patients were enrolled in 14 clinial studies of calciptriol. 1% tapinarof cream was superior to placebo [OR: 8.3 (5.5, 13.0), 8.3 (5.9, 13.0), 7.3 (5.1, 11.0)] and calcipotriol in the treatment of psoriasis at 4, 8, and 12 weeks, and the incidence of adverse events was higher than that with placebo [OR: 3.3 (2.6, 4.3)] and calcipotriol, with no serious systemic adverse events. 1% tapinarof cream is a safe and effective treatment for psoriasis. [ABSTRACT FROM AUTHOR]

Introduction Alopecia areata (AA) is a non-scarring, inflammatory type of hair loss, ranging in severity from patchy hair loss to alopecia totalis and universalis. Various treatment modalities are available for alopecia areata, including topical, intralesional, and systemic steroids, minoxidil, and systemic immunosuppressive. Multiple studies demonstrated the variable efficacy of vitamin D analogs in alopecia areata, but none have compared them with topical tacrolimus. Methods It was a randomized control trial conducted at Tehsil Headquarters Hospital TakhtBhai, Mardan. A total of 80 patients were enrolled in the study, 40 in each group. Using the technique of a consecutive non-probability sampling, patients were separated into groups A and B. Group A received topical calcipotriol (0.005%), while group B patients were treated with tacrolimus (0.1%). Both drugs were used twice a day for 6 months. Lesions are examined every month, and at the end of 6 months, a final SALT score is calculated. Results In our study, group A had 52% males and 48% females, while group B had 49% males and 51% females. The mean age was 32.6±6.7 and 31.5±7.4 in Group A and B respectively. The mean baseline SALT score in group A was 14.3±5.2 while in group B was13±5.1. On the other hand, the mean SALT score after 6 months was 6.2±2.3 in Group A and 8.5±5.6 in Group B. The efficacy in Group A came out to be 67%, while in group B 33% efficacy was noted (p-value=0.0132). Conclusion This study found that topical calcipotriol is superior to topical tacrolimus for hair growth in patients with alopecia areata. The difference was statistically significant. [ABSTRACT FROM AUTHOR]

Background and purpose: Psoriasis is an autoimmune inflammatory disease with major skin involvement. Calcipotriol as a vitamin-D analogue is one of the common drugs for topical treatment of psoriasis. Local drug delivery, due to higher concentration of drug at the sites of inflammation, is more effective and causes fewer systemic side effects. Limited skin penetration and durability of common topical formulations reduce the efficacy of treatment. In this study, we aimed to investigate the effect of solid lipid nanoparticles loaded with calcipotriol on local drug delivery. Materials and methods: In the present study, which is an interventional in vivo study, Solid Lipid Nanoparticle (SLN) was prepared by melting method and mixed with semi-solid base (cream). Then the effectiveness of the final formulation was investigated on the psoriasis model induced by imiquimod 5% in BALB/c mice. Three groups were included in this investigation: negative control (no treatment), positive control (conventional calcipotriol cream), and SLN (SLN cream with calcipotriol). Results: The results of the present study showed that, the SLN cream significantly reduced inflammatory scores compared to the other two groups on day five (P

The combined treatment with calcipotriol (Cal) and betamethasone dipropionate (BDP) has emerged as the leading anti-psoriatic topical treatment. Fixed-dose Cal/BDP is available in different formulations, including ointment, gel, foam, and cream. This review examines the mechanism of action of Cal/BDP underlying its therapeutic effect and compiles the evidence regarding its efficacy and safety compared to monotherapy with topical corticosteroids. The dual-action of Cal/BDP targets the inflammatory pathways and abnormal keratinocyte proliferation, both of them fundamental mechanisms of psoriasis pathogenesis. A large number of randomized, double-blind studies support Cal/BDP superiority over topical corticosteroids, demonstrating its broad efficacy across several degrees of psoriasis severity and its capability to provide early significant clinical improvements. This increased efficacy is achieved without negative effects on the safety profile, since the incidence of adverse effects reported with Cal/BDP is usually similar to that of BDP and even lower than that of Cal alone. The combination therapy rapid onset of action, coupled with a simplified dosing regimen, has been identified as crucial for improving long-term adherence and patient outcomes. In conclusion, Cal/BDP is confirmed as a versatile, effective, and convenient option for the patient in psoriasis management.

Background and purpose: Psoriasis is an autoimmune inflammatory disease with major skin involvement. Calcipotriol as a vitamin-D analogue is one of the common drugs for topical treatment of psoriasis. Local drug delivery, due to higher concentration of drug at the sites of inflammation, is more effective and causes fewer systemic side effects. Limited skin penetration and durability of common topical formulations reduce the efficacy of treatment. In this study, we aimed to investigate the effect of solid lipid nanoparticles loaded with calcipotriol on local drug delivery. Materials and methods: In the present study, which is an interventional in vivo study, Solid Lipid Nanoparticle (SLN) was prepared by melting method and mixed with semi-solid base (cream). Then the effectiveness of the final formulation was investigated on the psoriasis model induced by imiquimod 5% in BALB/c mice. Three groups were included in this investigation: negative control (no treatment), positive control (conventional calcipotriol cream), and SLN (SLN cream with calcipotriol). Results: The results of the present study showed that, the SLN cream significantly reduced inflammatory scores compared to the other two groups on day five (P<0.0001). In addition, drug loading into SLN significantly increased the rate of healing and reduced inflammation. Conclusion: This study showed that calcipotriol loading with SLN can improve the quality and the rate of treatment of skin lesions caused by psoriasis. [ABSTRACT FROM AUTHOR]

Objective To assess serum Vitamin D status in patients with alopecia areata (AA), its correlation with AA severity and efficacy of vitamin D3 analogues in such patients. Methods It was a randomized control trial. A total of 100 patients were selected using non provability consecutive sampling technique. Diagnosis of alopecia areata was confirmed on clinical and dermaoscopic features and severity of alopecia areata score (SALT) calculated. Serum Vitamin D levels were assed in all patients along with basic demographic data. All patients received topical calcipotriol (0.005%) twice a day for 6 months. Patients were called for monthly follow-up and final SALT score was calculated at the end of 6 months to assess the efficacy. P-value <0.05 was taken as significant. Results There were 100 cases of AA in total. The mean age was 30.5 ±8.4 with 42% male and 58% females. The mean SALT score at baseline was 20.7±5.4 and at the end of six months it decreased to 9.4±3.5s. Out of 100 patients 69 had low serum vit. D levels. Topical calcipotriol was effective in overall 71% patients using SALT50 as a measure of efficacy. Conclusion: It is concluded that Serum Vitamin D levels are lower significantly in patients with alopecia areata and vit. D3 analogues are effective in improving hair growth in such patients. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma (PDAC) is characterized by a dense extracellular matrix flooded with immune suppressive cells, resulting in extremely poor clinical response to immunotherapy. It has been revealed that the activation of pancreatic stellate cells (PSCs) makes considerable contributions to the immunological "cold" tumor microenvironment (TME). Herein, we developed a polyamino acid-based nanodrug incorporating the PSC activation inhibitor calcipotriol and anti-CXCL12 siRNA. The nanodrug was easily prepared with a small particle size and is capable of penetrating pancreatic tumors to inactivate PSCs and downregulate CXCL12. The in vivo results of orthotopic pancreatic tumor treatment demonstrated that codelivery of calcipotriol and anti-CXCL12 siRNA remodeled the PDAC TME with reduced extracellular matrix and decreased immunosuppressive T cells. Eventually, the infiltration of cytotoxic T cells was increased, thereby acting with immune checkpoint blockade (ICB) therapy for immunologically "cold" pancreatic tumors. In the present study, we propose a promising paradigm to improve the immunotherapy outcome of PDAC using nanodrugs that synchronously inhibit PSC activation and regulatory T-cell infiltration. Pancreatic ductal adenocarcinoma (PDAC) is characterized by a dense extracellular matrix (ECM) that impedes the tumor infiltration of therapeutic agents and cytotoxic T lymphocytes, resulting in a poor clinical response to immunotherapy. In the present study, we proposed a promising approach for enhanced immunotherapy of pancreatic cancer. Specifically, a nanodrug incorporating calcipotriol and anti-CXCL12 siRNA was synthesized to synchronously inactivate matrix-producing pancreatic stellate cells and suppress the infiltration of regulatory T cells. The reduced ECM removed the pathological barrier, preventing nanodrug penetration and effector T-cell infiltration, leading to a conversion of the immunosuppressive "cold" microenvironment to a "hot" microenvironment, which eventually boosted the immunotherapy of anti-PD-1 antibodies in pancreatic cancer. [Display omitted] [ABSTRACT FROM AUTHOR]

Calcipotriol (CAL) has been widely studied as a fibrosis inhibitor and used to treat plaque psoriasis via transdermal administration. The clinical application of CAL to treat liver fibrosis is bottlenecked by its unsatisfactory pharmacokinetics, biodistribution, and side effects, such as hypercalcemia in patients. The exploration of CAL as a safe and effective antifibrotic agent remains a major challenge. Therefore, we rationally designed and synthesized a self‐assembled drug nanoparticle encapsulating CAL in its internal hydrophobic core for systematic injection (termed NPs/CAL) and further investigated the beneficial effect of the nanomaterial on liver fibrosis. C57BL/6 mice were used as the animal model, and human hepatic stellate cell line LX‐2 was used as the cellular model of hepatic fibrogenesis. Immunofluorescence staining, flow cytometry, western blotting, immunohistochemical staining, and in vitro imaging were used for evaluating the efficacy of NPs/CAL treatment. We found NPs/CAL can be quickly internalized in vitro, thus potently deactivating LX‐2 cells. In addition, NPs/CAL improved blood circulation and the accumulation of CAL in liver tissue. Importantly, NPs/CAL strongly contributed to the remission of liver fibrosis without inducing hypercalcemia. Overall, our work identifies a promising paradigm for the development of nanomaterial‐based agents for liver fibrosis therapy. [ABSTRACT FROM AUTHOR]

Abstract is missing (Short communication)

Background Psoriasis is a chronic skin disease, and topical sequential therapy with a combination of calcipotriol and calcipotriol betamethasone is currently approved topical treatment. However, the exact mechanism by which this treatment regimen relieves psoriasis is unknown. Method We assembled a cohort of 65 psoriasis patients and divided post-treatment cohort into responder group and non-responder group according to the Psoriasis Area Severity Index (PASI) score after 12-week treatment. We measured the expression levels of proteins in collected 130 serum samples using our in-depth proteomics platform with a data-independent acquisition mass spectrometer and antibody microarray. We performed bioinformatics analyses of the biologic processes and signaling pathways that were changed in the responder group and constructed a proteomics landscape of psoriasis pathogenesis response to treatment. We then validated the biomarkers of disease severity in an independent cohort of 88 samples using an enzyme-linked immunosorbent assay. Results We first identified 174 differentially expressed proteins (DEPs) for comparative analysis of proteins between responders and non-responders at baseline (p

Background: Vitamin D analogues and NBUVB are both well‐recognised modes of therapy in the treatment of chronic stable plaque psoriasis. The objective of this open label intraindividual, left right study was to compare two different vitamin D analogues, calcipotriol and calcitriol, in combination with NBUVB phototherapy in psoriasis. Methods: Thirty patients with stable plaque psoriasis were enrolled for a 12‐week clinical trial. The target lesion on the left side was treated topically with calcitriol ointment, while that on the right side was treated with calcipotriol ointment once daily. The whole body was irradiated with narrow‐band ultraviolet B phototherapy (NBUVB) three times per week. Efficacy was assessed by target plaque scoring. Results: Both therapies resulted in a statistically significant reduction in erythema, scaling, thickness, and target plaque score, seen as early as 2 weeks into therapy. However, the calcipotriol combination led to an earlier clearance of plaques and a lesser relapse rate than the calcitriol combination. The number of treatment sessions and cumulative NBUVB doses were significantly lower in the calcipotriol‐treated group. Conclusion: Both vitamin D analogues appear to be safe, effective, and cosmetically acceptable, with calcipotriol being more efficacious, well tolerated, with a rapid onset of action and a better maintenance of response. [ABSTRACT FROM AUTHOR]

A disposable stochastic platform based on calix [6]arene modified multi-walled carbon nanotubes-gold nanoparticles screen-printed electrode has been developed for the simultaneous determination of calcipotriol and betamethasone. For both analytes, very wide linear concentration ranges and extremely low limits of quantification (LOQ) were obtained: from 1.0 × 10−15 to 1.0 × 10−3 mol L−1 and with a 1.0 × 10−15 mol L−1 LOQ for calcipotriol, and from 1.0 × 10−16 to 1.0 × 10−2 mol L−1 with a 1.0 × 10−16 mol L−1 LOQ for betamethasone. The applicability of the sensing platform was successfully tested in commercially available topical pharmaceutical gel and surface water samples, obtaining recovery values ranging from 99.10 to 99.99% and relative standard deviation values under 0.05%. The obtained results render the proposed platform a viable, robust, selective, and sensitive tool that can be employed for the determination of the analytes in on-site routine quality control of pharmaceuticals and water quality monitoring. [ABSTRACT FROM AUTHOR]

Abstract Calcipotriol (CAL) has been widely studied as a fibrosis inhibitor and used to treat plaque psoriasis via transdermal administration. The clinical application of CAL to treat liver fibrosis is bottlenecked by its unsatisfactory pharmacokinetics, biodistribution, and side effects, such as hypercalcemia in patients. The exploration of CAL as a safe and effective antifibrotic agent remains a major challenge. Therefore, we rationally designed and synthesized a self‐assembled drug nanoparticle encapsulating CAL in its internal hydrophobic core for systematic injection (termed NPs/CAL) and further investigated the beneficial effect of the nanomaterial on liver fibrosis. C57BL/6 mice were used as the animal model, and human hepatic stellate cell line LX‐2 was used as the cellular model of hepatic fibrogenesis. Immunofluorescence staining, flow cytometry, western blotting, immunohistochemical staining, and in vitro imaging were used for evaluating the efficacy of NPs/CAL treatment. We found NPs/CAL can be quickly internalized in vitro, thus potently deactivating LX‐2 cells. In addition, NPs/CAL improved blood circulation and the accumulation of CAL in liver tissue. Importantly, NPs/CAL strongly contributed to the remission of liver fibrosis without inducing hypercalcemia. Overall, our work identifies a promising paradigm for the development of nanomaterial‐based agents for liver fibrosis therapy.

Objective The aim of the study is to compare the efficacy of topical calcipotriol (0.005%) and topical anthralin (0.5%) in treatment of Chronic Plaque Psoriasis (CPP). Methods This randomized, interventional study was conducted at Pak Emirates Military Hospital, Rawalpindi and Combined Military Hospital, Rawalpindi for 6-month period (10th January 2020 to 10th July 2020). A sample of 186 patients was randomly distributed in two groups. In group A, patients applied topical anthralin (0.5%) every night for 12 weeks. In group B, patients applied topical calcipotriol (0.005%) every night for 12 weeks. The follow up period was 12 weeks and assessment of the efficacy was done at 4, 8 and 12 weeks by utilizing PASI score. Results The age range of the individuals was from 15 to 50 years. The average duration of presenting complaint for Group A was 8.903±1.85 months while for Group B was 9.193±2.58 months. In Group A, the average PASI score before and after the treatment was 16.22±3.02 and 4.784±3.28 respectively and in Group B the average PASI score before and after the treatment was 16.03±2.09 and 2.376±2.39 respectively. The number of male patients in each group was more than female. Efficacy i.e. reduction in PASI score by 75% was seen in 21.5% patients of Group A as compared to 43% in Group B (p=0.001). Conclusion In conclusion, 0.005% calcipotriol is considerably more efficacious than 0.5% anthraline in bringing disease improvement and patient satisfaction than 0.5% anthraline. [ABSTRACT FROM AUTHOR]

Background: In psoriasis, poor treatment adherence is frequently related to low efficacy and limited cosmetic acceptability from the patients’ perspective. This study aimed to characterize the sensorial attributes of a calcipotriol (CAL) and betamethasone dipropionate (BDP)-cream vehicle based on polyaphron dispersion (PAD) Technology and to compare them with the conventional ointment and oleogel formulations for psoriasis. Methods: A panel of 16 experts assessed sensory properties at four different stages: appearance, pick up, rub out and afterfeel. Descriptive sensory analysis was used to evaluate relevant attributes. Each attribute was rated on a line scale (range 0–100%). Active ingredients were not used because panellists were healthy volunteers, and vehicle formulations needed to be used instead. Results: CAL/BDP PAD-cream vehicle was evaluated as having a low stickiness, low grease behaviour, good wetness, and good spreadability. Ointment showed the least desirable behaviour regarding these properties. Moreover, once CAL/BDP PAD-cream vehicle was absorbed, the gloss disappeared quickly, leaving low stickiness and a low amount of residue. This afterfeel behaviour was not observed with ointment. The oleogel formulation had good sensory properties, similar to CAL/BDP PAD-cream vehicle, but with lower integrity of shape, lower wetness and higher greasiness. Conclusion: Overall, CAL/BDP PAD-cream vehicle has the desirable requirements for a topical product for the treatment of psoriasis, with better sensory properties than ointment and easier manipulation than oleogel, which may lead to greater acceptance and adherence.

Abstract Aim MC903 is a synthetic derivative of vitamin D3 that has been designed to diminish its impact on calcium metabolism and is clinically used as a transdermal reagent for psoriasis. Animal studies showed that an oral or intraperitoneal vitamin D3 treatment prevented the development of obesity. In contrast, the bioavailability of orally administered vitamin D3 is reported to be low in obese patients. In the current study, we aimed to investigate the impact of a transdermal treatment with MC903 in established obese mice. We further studied the underlying mechanisms of MC903-mediated metabolic improvement. Materials and methods Male C57BL/6 J mice were fed standard chow or a 60% high-fat diet (HFD) for 7 weeks, and a transdermal treatment with MC903 on the ear auricle was initiated thereafter. The metabolic profiles of mice were analyzed during 4 weeks of treatment, and mice were dissected for histological and gene expression analyses. The direct impacts of MC903 and vitamin D3 were investigated using 3T3-L1 adipocytes and C2C12 myotubes in vitro. Results HFD-fed mice showed significant increases in body and epididymal white adipose tissue (eWAT) weights with enlarged adipocytes. They exhibited glucose intolerance, decreased oxygen consumption, and chronic inflammation in eWAT. The transdermal treatment with MC903 significantly ameliorated these metabolic abnormalities in HFD-fed mice without affecting food consumption. In accordance with enhanced energy metabolism, myofiber diameters and the expression of uncoupling protein 3 (UCP3) in the gastrocnemius and soleus muscle were significantly increased in MC903-treated HFD mice. In addition, vitamin D3 and MC903 both suppressed adipogenic differentiation and enhanced lipolysis in 3T3-L1 adipocytes, and increased UCP3 expression in cultured C2C12 myotubes. Furthermore, MC903 increased oxygen consumption and UCP3 knockdown significantly decreased them in C2C12 myotubes. Conclusions A transdermal treatment with MC903 increased myofiber diameter and energy metabolism and decreased visceral fat accumulation, thereby improving obesity and glucose intolerance in mice.

Objective(s): A new binary mixture containing mometasone furoate (MF) and calcipotriol (CP) is suggested to manage psoriasis; since the combined stability profile of these drugs is poorly understood.Materials and Methods: Herein MF, CP, and their mixtures were subjected to various stress conditions. Also, stability-indicating HPLC was developed and validated according to ICH guidelines with Box-Behnken design. The degradation products (DPs) were predicted in silico and identified using LC-MS. The bioactivity and toxicity of DPs were studied using molecular docking and alamarBlue assay, respectively. Spectroscopic techniques of the first derivative, first-derivative ratio, and the mean-centering of ratio spectra were also used to determine MF and CP in the mixture because of spectra overlapping. Results: The major degradants for MF in alkaline conditions were DP1, DP2, and DP3, while in thermal and UV conditions, only DP1 was generated. CP gave one degradant in all conditions. No new impurity was observed in the MF and CP mixtures. The results of spectrophotometry showed good linearity in the range of 4-50 and 2-20 µg/ml, while linearity for HPLC was in the range of 4–50 and 0.5–2.5 µg/ml for MF and CP, respectively. Recovery was 99.61–100.38% for UV and 100.4% for HPLC methods of MF and 100.6–101.4% for UV and 99.5% for HPLC methods of CP.Conclusion: The developed methods can be used as simple, accurate, precise, and rapid techniques for routine quality control of MF and CP mixtures.

Seborrheic keratosis is the most common slow‐growing, benign epithelial tumour, usually appearing on sun‐exposed areas. Treatment modalities for seborrheic keratosis may be uncomfortable and/or time‐consuming. We present a case series of 12 patients with solitary seborrheic keratosis localized on the face treated with 0.005% calcipotriol ointment. The treatment lasted 3–8 months and resulted in complete regression of the lesions. Remission (follow‐up period) lasted from 6 to 10 years. We conclude that topical calcipotriol may be a useful treatment option for seborrheic keratosis. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is an allergic disease mediated by Th2 cells. In AD, externally stimulated keratinocytes release inflammatory cytokines, such as IL‐33 and TSLP. Inflammatory cells infiltrate skin tissue and increase vascular permeability. Therefore, we hypothesized that imatinib mesylate (IMT), which suppresses vascular permeability, may be a candidate therapeutic agent for AD. A vitamin D3 analog (MC903) was administered daily to both ears of Balb/c mice to create a murine AD model to which IMT was applied. The skin lesions were evaluated histopathologically and by immunostaining. Cytokine expression in the skin was assessed by using real‐time polymerase chain reaction (PCR) and immunostaining and was investigated using Evans Blue to determine whether IMT suppressed vascular permeability due to histamine. The suppressive effect of TNF‐α/IL‐4‐induced TSLP expression in primary mouse keratinocytes (MKCs) treated with IMT was then investigated. Tslp gene and protein expression in the lesion was measured using real‐time PCR and ELISA. The activation of signal transduction was analysed by western blotting. Topical application of IMT significantly reduced ear thickness, Evans blue leakage, and scratch onset. IMT suppressed the number of infiltrating cells (CD4+ T cells, eosinophils, and basophils), and the expression of IL‐13, IL‐33, and TSLP in a MC903‐induced, murine AD model and inhibited TNF‐α/IL‐4‐induced TSLP expression via downregulation of ERK phosphorylation in MKCs. IMT reduced the skin symptoms in a MC903‐induced, murine AD model, suggesting that it may have potential as a new treatment for AD. [ABSTRACT FROM AUTHOR]

Oxidative stress due to excessive reactive oxygen species (ROS) production in the skin microenvironment is one of the main mechanisms in psoriasis pathogenesis. A nano drug delivery system based on ROS-responsive release can enhance drug release at the target site. In this study, a ROS-sensitive material methoxypolyethylene glycol-thioether-thiol (mPEG-SS) was synthesized using mPEG as the parent structure with sulfide structural modification. An mPEG-SS-calcipotriol (mPEG-SS-CPT, PSC) nano-micelle percutaneous delivery system was prepared by encapsulating CPT. A small animal imaging system was used to study PSC’s the ROS-sensitive drug release process. It is shown that endogenous ROS mainly affects PSC and releases drugs. Finally, the therapeutic effect of PSC on psoriasis was explored by animal experiments. Ultimately, it ameliorates imiquimod-induced psoriasis-like inflammation. Overall, PSC is an effective ROS-sensitive transdermal drug delivery system that is expected to provide a new strategy for treating psoriasis.

Background and objectives Once-daily, fixed-combination calcipotriol 50 μg/g (Cal) plus betamethasone dipropionate 0.5 mg/g (BD) is available in aerosol foam and cream formulations. As no head-to-head data are available, we use a matching-adjusted indirect comparison (MAIC) approach to compare Cal/BD foam and cream. Methods Anchored and unanchored MAIC analyses were conducted using individual patient data (IPD) from five Cal/BD foam trials and two trials of Cal/BD cream. Outcomes of interest were the proportion of patients with Physician's Global Assessment (PGA) success and the mean reduction in modified Psoriasis Area and Severity Index (mPASI). Results In the anchored MAIC, patients were more likely to achieve PGA success after 4 weeks of Cal/BD foam than after 8 weeks of Cal/BD cream and had larger mean improvements in mPASI (p

Psoriasis is a chronic inflammatory disease affecting about 100 million people worldwide. Around 80% of patients can be treated with topical agents, most commonly corticosteroids and vitamin D analogues. A topical foam formulation of calcipotriol (50 μg/g) and betamethasone dipropionate (0.5 mg/g) (Cal/BD foam; Enstilar®) is approved for the daily treatment of psoriasis for up to 4 weeks and twice-weekly thereafter as maintenance treatment (after initial 4-week treatment success). Long-term proactive maintenance with Cal/BD foam for plaque psoriasis has been shown to prolong the time to first relapse, reduce the number of relapses and increase days in remission in the PSO-LONG trial. Four case studies of proactive management with Cal/BD foam for the treatment of plaque psoriasis for up to 12 months from initial presentation are described. These case studies provide real-world evidence on the long-term effectiveness of proactive management with Cal/BD foam as well as the improvement and maintenance of health-related quality of life. Cal/BD foam was well tolerated.

Actinic keratosis (AK) is among the most commonly diagnosed skin diseases with potentially life-threatening repercussions if left untreated. Usage of pharmacologic agents represents one of many therapeutic strategies that can be used to help manage these lesions. Ongoing research into these compounds continues to change our clinical understanding as to which agents most benefit particular patient populations. Indeed, factors such as past personal medical history, lesion location and tolerability of therapy only represent a few considerations that clinicians must account for when prescribing appropriate treatment. This review focuses on specific drugs used in either the prevention or treatment of AKs. Nicotinamide, acitretin and topical 5-fluorouracil (5-FU) continue to be used with fidelity in the chemoprevention of actinic keratosis, although some uncertainty persists in regard to which agents should be used in immunocompetent vs. immunodeficient/immunosuppressed patients. Topical 5-FU, including combination formulations with either calcipotriol or salicylic acid, as well as imiquimod, diclofenac and photodynamic light therapy are all accepted treatment strategies employed to target and eliminate AKs. Five percent of 5-FU is regarded as the most effective therapy in the condition, although the literature has conflictingly shown that lower concentrations of the drug might also be as effective. Topical diclofenac (3%) appears to be less efficacious than 5% 5-FU, 3.75–5% imiquimod and photodynamic light therapy despite its favorable side effect profile. Finally, traditional photodynamic light therapy, while painful, appears to be of higher efficacy in comparison to its more tolerable counterpart, daylight phototherapy. [ABSTRACT FROM AUTHOR]

Background and aim: Clinical trials have demonstrated the efficacy of fixed-dose combination calcipotriol/betamethasone (Cal/BD) aerosol foam for the treatment of patients with scalp psoriasis. However, data on the real-world effectiveness of Cal/BD aerosol foam in this subgroup of patients are lacking. Therefore, this study investigated the effectiveness and tolerability of 4 weeks' treatment with Cal/BD aerosol foam in patients with scalp psoriasis in everyday clinical practice. Methods: This prospective, non-interventional multicenter study involved 217 adults with scalp psoriasis who were treated with Cal/BD aerosol foam for 4 weeks. Primary endpoints included the proportion of patients with <10% of the scalp area affected (Scalp-BSA) plus a Scalp-PGA of "mild" after 4 weeks, as well as the proportion of patients with an absolute PSSI ≤2 points after 4 weeks. Secondary endpoints included patient reported changes in erythema, itching, flaking, and thickness at baseline, 3 days, 1 week, 2 weeks, and 4 weeks. Results: After 4 weeks, 53.4% of patients treated with Cal/BD aerosol foam had achieved a Scalp-BSA of <10% and a mild Scalp-PGA. Furthermore, 47.6% of patients achieved a PSSI ≤2. Improvements in pruritus and other symptoms (induration, erythema, and scaling) were seen already within 3 days. The proportion of patients who reported that scalp psoriasis had no influence on their quality of life (Dermatology Quality of Life Index 0/1 points) increased from 3.2% at baseline to 47.9% at study end. Patient satisfaction with treatment was high (Treatment Satisfaction Questionnaire-9 scores of 74.5 ± 27.1 for effectiveness, 72.0 ± 25.2 for ease of use, and 77.8 ± 24.2 for general satisfaction). Overall, 97.4% of HCPs assessed the tolerability of Cal/BD aerosol foam as good/very good with no new safety concerns. Conclusion: This study demonstrated the effectiveness, rapid onset of action, good tolerability, and good safety profile of the Cal/BD aerosol foam in patients with scalp psoriasis treated in a real-world setting. [ABSTRACT FROM AUTHOR]

Aim: MC903 is a synthetic derivative of vitamin D3 that has been designed to diminish its impact on calcium metabolism and is clinically used as a transdermal reagent for psoriasis. Animal studies showed that an oral or intraperitoneal vitamin D3 treatment prevented the development of obesity. In contrast, the bioavailability of orally administered vitamin D3 is reported to be low in obese patients. In the current study, we aimed to investigate the impact of a transdermal treatment with MC903 in established obese mice. We further studied the underlying mechanisms of MC903-mediated metabolic improvement. Materials and methods: Male C57BL/6 J mice were fed standard chow or a 60% high-fat diet (HFD) for 7 weeks, and a transdermal treatment with MC903 on the ear auricle was initiated thereafter. The metabolic profiles of mice were analyzed during 4 weeks of treatment, and mice were dissected for histological and gene expression analyses. The direct impacts of MC903 and vitamin D3 were investigated using 3T3-L1 adipocytes and C2C12 myotubes in vitro. Results: HFD-fed mice showed significant increases in body and epididymal white adipose tissue (eWAT) weights with enlarged adipocytes. They exhibited glucose intolerance, decreased oxygen consumption, and chronic inflammation in eWAT. The transdermal treatment with MC903 significantly ameliorated these metabolic abnormalities in HFD-fed mice without affecting food consumption. In accordance with enhanced energy metabolism, myofiber diameters and the expression of uncoupling protein 3 (UCP3) in the gastrocnemius and soleus muscle were significantly increased in MC903-treated HFD mice. In addition, vitamin D3 and MC903 both suppressed adipogenic differentiation and enhanced lipolysis in 3T3-L1 adipocytes, and increased UCP3 expression in cultured C2C12 myotubes. Furthermore, MC903 increased oxygen consumption and UCP3 knockdown significantly decreased them in C2C12 myotubes. Conclusions: A transdermal treatment with MC903 increased myofiber diameter and energy metabolism and decreased visceral fat accumulation, thereby improving obesity and glucose intolerance in mice. [ABSTRACT FROM AUTHOR]

Psoriasis is a chronic skin disease, and topical sequential therapy with a combination of calcipotriol and calcipotriol betamethasone is currently approved topical treatment. However, the exact mechanism by which this treatment regimen relieves psoriasis is unknown. We assembled a cohort of 65 psoriasis patients and divided post-treatment cohort into responder group and non-responder group according to the Psoriasis Area Severity Index (PASI) score after 12-week treatment. We measured the expression levels of proteins in collected 130 serum samples using our in-depth proteomics platform with a data-independent acquisition mass spectrometer and antibody microarray. We performed bioinformatics analyses of the biologic processes and signaling pathways that were changed in the responder group and constructed a proteomics landscape of psoriasis pathogenesis response to treatment. We then validated the biomarkers of disease severity in an independent cohort of 88 samples using an enzyme-linked immunosorbent assay. We first identified 174 differentially expressed proteins (DEPs) for comparative analysis of proteins between responders and non-responders at baseline (p < 0.05). Then pathway analysis showed that the responders focused more on signaling molecules and interaction, complement and coagulation cascades, whereas the non-responders more on signal transduction and IL-17 signaling pathways. We further identified four candidate biomarkers (COLEC11, C1QA, BNC2, ITIH4) response to treatment. We also found 125 DEPs (p < 0.05) after treatment compared with before treatment in responder group. Pathway analysis showed an enrichment in pathways related to complement and coagulation cascades, phagosome, ECM-receptor interaction, cholesterol metabolism, vitamin digestion and absorption. CD14 was validated as potential biomarkers for the disease severity of psoriasis and treatment targets. In this work, we analyzed the response to topical sequential therapy and finally identified four biomarkers. Additionally, we found that topical sequential therapy may alleviate psoriasis by regulating lipid metabolism and modulating the immune response by affecting the complement activation process. [ABSTRACT FROM AUTHOR]

Calcipotriol, a vitamin D analogue, is an antiproliferative and anti‐inflammatory drug currently used in psoriasis. Here, our aim was to analyse the safety of calcipotriol for cartilage and bone in alleviated‐dose (0.1 mg instead of usual ≥1mg dose) zymosan‐induced arthritis in rats. Theoretically, high doses of vitamin D or analogues could have detrimental effects on bone or cartilage. The rats were divided into four groups: vehicle (n = 9), dexamethasone 0.1 mg/kg (n = 9), calcipotriol 0.1 mg/kg (n = 8) and negative control (n = 10) with no injections. Arthritic rats were given phosphate‐buffered saline (PBS) injections to left knees as a control. After euthanasia on day 8, all knees were imaged with micro‐computed tomography for surface lesions and decalcified for histological analyses. Contrary to our expectations, no significant changes could be observed in the tomography data and histological scores among the three treatment groups or between the vehicle‐treated and non‐arthritic group. Calcipotriol did not cause adverse effects on cartilage or subchondral bone within a week, suggesting that it could be safely used in local treatment of arthritis. The alleviated model caused synovitis with local and systemic inflammatory response without cartilage erosions, which might be useful in studying self‐limiting synovitis where cartilage or bone effects are not of primary interest. [ABSTRACT FROM AUTHOR]

Objective(s): A new binary mixture containing mometasone furoate (MF) and calcipotriol (CP) is suggested to manage psoriasis; since the combined stability profile of these drugs is poorly understood. Materials and Methods: Herein MF, CP, and their mixtures were subjected to various stress conditions. Also, stability-indicating HPLC was developed and validated according to ICH guidelines with Box-Behnken design. The degradation products (DPs) were predicted in silico and identified using LC-MS. The bioactivity and toxicity of DPs were studied using molecular docking and alamarBlue assay, respectively. Spectroscopic techniques of the first derivative, first-derivative ratio, and the meancentering of ratio spectra were also used to determine MF and CP in the mixture because of spectra overlapping. Results: The major degradants for MF in alkaline conditions were DP1, DP2, and DP3, while in thermal and UV conditions, only DP1 was generated. CP gave one degradant in all conditions. No new impurity was observed in the MF and CP mixtures. The results of spectrophotometry showed good linearity in the range of 4-50 and 2-20 µg/ml, while linearity for HPLC was in the range of 4-50 and 0.5-2.5 µg/ml for MF and CP, respectively. Recovery was 99.61-100.38% for UV and 100.4% for HPLC methods of MF and 100.6-101.4% for UV and 99.5% for HPLC methods of CP. Conclusion: The developed methods can be used as simple, accurate, precise, and rapid techniques for routine quality control of MF and CP mixtures. [ABSTRACT FROM AUTHOR]

Objective In PSO-LONG, long-term proactive management (PAM) of psoriasis with fixed-dose combination calcipotriol 50 µg/g and betamethasone dipropionate 0.5 mg/g (Cal/BD) aerosol foam was superior to conventional reactive management. This post-hoc analysis investigated long-term PAM with Cal/BD foam in PSO-LONG patients who could be more susceptible to corticosteroid-induced hypothalamic-pituitary-adrenal (HPA) axis suppression. Methods Efficacy and safety of PAM with Cal/BD foam (twice-weekly) versus reactive management (twice-weekly vehicle foam), with once-daily rescue Cal/BD foam for four weeks following relapse, was assessed in the HPA subgroup (n = 66); patients had moderate-to-severe psoriasis (physician global assessment score ≥3; 10–30% body surface area affected). Primary endpoint was time to first relapse. Results PAM with Cal/BD foam was associated with longer median time to first relapse (111 versus 31 days), reduced risk of first relapse (hazard ratio: 0.49; p = .029), greater proportion of days in remission (17%; p = .001) and reduced rate of relapse (60% reduction; p

About 70-80% of the patients with psoriasis have confined, localized diseases and are managed with topical treatments alone. The selection of a topical therapy should be based on patient expectations and peculiarities as well as lesion characteristics such as lesion localization and infiltration, degree of erythema, and amount of squamae. Pharmacological drug formulations are also extremely important in the efficacy of topical therapy. Topical treatment options include corticosteroids, vitamin D analogs, tazarotene, calcineurin inhibitors, salicylic acid, anthralin, and various combinations.

Once-daily, fixed-combination calcipotriol 50 μg/g (Cal) plus betamethasone dipropionate 0.5 mg/g (BD) is available in aerosol foam and cream formulations. As no head-to-head data are available, we use a matching-adjusted indirect comparison (MAIC) approach to compare Cal/BD foam and cream. Anchored and unanchored MAIC analyses were conducted using individual patient data (IPD) from five Cal/BD foam trials and two trials of Cal/BD cream. Outcomes of interest were the proportion of patients with Physician's Global Assessment (PGA) success and the mean reduction in modified Psoriasis Area and Severity Index (mPASI). In the anchored MAIC, patients were more likely to achieve PGA success after 4 weeks of Cal/BD foam than after 8 weeks of Cal/BD cream and had larger mean improvements in mPASI (p <.01 in EU mPASI analysis). In unanchored analyses, 4 weeks of Cal/BD foam treatment was statistically significantly more efficacious in inducing PGA success than 8 weeks of Cal/BD cream (p <.01 in five of six comparisons). Mean reductions in mPASI were consistently statistically significantly greater with Cal/BD foam than with Cal/BD cream. Use of Cal/BD foam consistently shows significantly greater improvements in PGA and mPASI outcomes, compared with Cal/BD cream. [ABSTRACT FROM AUTHOR]

Introduction: To date, there have been no head-to-head clinical studies comparing calcipotriol 0.005% plus betamethasone dipropionate 0.064% (Cal/BD) aerosol foam and halobetasol propionate 0.01% plus tazarotene 0.045% (HP/Taz) lotion for the treatment of plaque psoriasis. However, the efficacy of 4 weeks of Cal/BD foam and 8 weeks of HP/Taz lotion has been compared using a matching-adjusted indirect comparison (MAIC) approach. Here, we compare the efficacy and safety of Cal/BD foam and HP/Taz lotion for up to 52 weeks. Methods: An unanchored MAIC was conducted using individual patient data from the PSO-LONG Cal/BD foam trial and a 52-week, open-label phase 3 study of HP/Taz lotion (NCT02462083). Key outcomes of interest were Physician's Global Assessment (PGA) success (PGA 0/1 with ≥ 2-point improvement) after 4 or 8 weeks of open-label therapy; the proportion of patients who had body surface area affected (BSA) ≤ 3 after open-label therapy who maintained BSA ≤ 3 to week 52; and adverse events (AEs). Results: After matching, patients were statistically significantly more likely to have PGA success after 4 weeks of Cal/BD foam than after 8 weeks of HP/Taz lotion (84.5% versus 54.4%; p < 0.01). At week 52, 92.5% and 92.4% of patients receiving proactive and reactive Cal/BD foam, respectively, maintained BSA ≤ 3, compared with 49.3% of those treated with HP/Taz lotion (both p < 0.01). Treatment-related AEs, AEs leading to withdrawal, and AEs associated with drug application (dermatitis, application site pain, and pruritus) were significantly rarer with Cal/BD foam than with HP/Taz lotion (all p < 0.01). Conclusions: Cal/BD aerosol foam demonstrated significantly greater efficacy than HP/Taz lotion, and had a more favorable safety profile, compared with HP/Taz lotion, for up to 52 weeks. Proactive Cal/BD foam maintenance therapy and reactive use of Cal/BD foam following relapse both had significant advantages over HP/Taz lotion. [ABSTRACT FROM AUTHOR]

Background: Psoriasis Vulgaris is a common immune‐mediated skin disease. Its high prevalence, disability, chronicity, disfiguration, and associated comorbidities make it a challenge for physicians. Topical agents remain the mainstay of treatment for patients with mild to moderate psoriasis. Aim: To evaluate the efficacy and tolerability of topical methotrexate 1% gel (MTX) versus topical calcipotriol 0.005% cream (CPL) in the treatment of localized plaque psoriasis. Methods: This prospective comparative study included 40 patients with localized plaque psoriasis instructed to apply MTX to one side (group A) and CPL to the other side lesions (group B) twice daily for 12 weeks. Clinical and dermoscopic evaluations before, weekly during and after 3 months of treatment were done. The immunohistopathological assessment was done for skin biopsies from 10 patients in each group before and after treatment. Results: At the end of 12 weeks, there was marked‐complete improvement in 97.5% of group A lesions treated with MTX 1% gel compared with 37.5% of group B lesions treated with calcipotriol 0.005% cream (p < 0.001). There was a very high statistically significant improvement in erythema that was cleared totally in 67.5% vs 22.5%, scaling in 75% vs 17.5%, and infiltration in 72.5% vs 27.5% in group A vs B, respectively (p < 0.001). These results were confirmed by dermoscopic and immunohistopathological findings. Conclusion: Methotrexate 1% gel is a marvelous promising well‐tolerated effective topical agent that can be used safely in the treatment of localized plaque psoriasis. [ABSTRACT FROM AUTHOR]

Pancreatic cancer resistance to immunotherapies is partly due to deficits in tumor-infiltrating immune cells and stromal density. Combination therapies that modify stroma and recruit immune cells are needed. Vitamin D analogs such as calcipotriol (Cal) decrease fibrosis in pancreas stroma, thus allowing increased chemotherapy delivery. OVs infect, replicate in, and kill cancer cells and recruit immune cells to immunodeficient microenvironments. We investigated whether stromal modification with Cal would enhance oncolytic viroimmunotherapy using recombinant orthopoxvirus, CF33. We assessed effect of Cal on CF33 replication using pancreas ductal adenocarcinoma (PDAC) cell lines and in vivo flank orthotopic models. Proliferation assays showed that Cal did not alter viral replication. Less replication was seen in cell lines whose division was slowed by Cal, but this appeared proportional to cell proliferation. Three-dimensional in vitro models demonstrated decreased myofibroblast integrity after Cal treatment. Cal increased vascular lumen size and immune cell infiltration in subcutaneous models of PDAC and increased viral delivery and replication. Cal plus serial OV dosing in the syngeneic Pan02 model caused more significant tumor abrogation than other treatments. Cal-treated tumors had less dense fibrosis, enhanced immune cell infiltration, and decreased T cell exhaustion. Calcipotriol is a possible adjunct for CF33-based oncolytic viroimmunotherapy against PDAC.

Psoriasis is a chronic inflammatory skin disease. Vitamin D analogues are the first-line topical agents for the long-term management of psoriasis. Chinese herbal medicine (CHM) bath therapy is commonly employed for psoriasis. However, the effects and safety of CHM bath therapy for psoriasis vulgaris, using topical calcipotriol as the comparator, remain inconclusive. Furthermore, the combination of herbs, a distinctive feature of CHM, is essential for its therapeutic effects due to the individual and synergistic properties of the herbs involved. The review was conducted to evaluate the effectiveness and safety of CHM bath therapy for psoriasis vulgaris, using calcipotriol as the comparator. Potential herbs and herb combinations of CHM bath therapy were also explored for further drug discovery. Nine databases were searched from inception until March 05, 2024. Randomised controlled trials (RCTs) investigating CHM bath therapy, using calcipotriol as the comparator, were included. Statistical analyses were performed using RevMan 5.4, Stata 12.0 and SPSS Clementine 12.0 software. The evidence certainty for outcomes was assessed using the approach proposed by the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group. Moreover, association rule analysis on herbs identified in the systematic review was conducted to explore the potential herbs and herb combinations. A total of 17 RCTs involving 1,379 participants were included in this systematic review. The findings of this review revealed that: 1) CHM bath therapy produced comparable effects to calcipotriol in reducing Psoriasis Area and Severity Index (PASI), Psoriasis Scalp Severity Index (PSSI), and itch visual analogue scale (VAS) at the end of the treatment phase; as well as exhibited a superior long-term effect than calcipotriol through decreasing relapse rates at the end of the follow-up phase; 2) CHM bath therapy showed an additional benefit when combined with calcipotriol in managing psoriasis vulgaris at the end of the treatment phase, in terms of PASI, PSSI, itch VAS, IL-17, IL-23, CD3+ and CD4+ T cells. The certainty of the evidence was rated as 'very low', 'low' or 'moderate' based on the GRADE assessment, considering some concerns or high risk of bias of included studies, substantial heterogeneity, and existing publication bias of some outcomes. Additionally, the proportions of participants reporting adverse events were similar in both groups. Association rule analysis of all included herbs identified 23 herb combinations including Prunus persica (L.) Batsch and Carthamus tinctorius L., as well as 11 frequently used herbs, such as Kochia scoparia (L.) Schrad., Dictamnus dasycarpus Turcz. And Sophora flavescens Ait. The effects of CHM bath therapy were comparable with those of topical calcipotriol but demonstrated a longer-lasting effect. Combining CHM bath therapy with calcipotriol also provided an additional benefit for adult psoriasis vulgaris. However, the certainty of the evidence was downgraded due to the methodological limitations of included studies. To confirm the findings of this review, future investigations should involve double-blinded, placebo-controlled RCTs. Importantly, it appears worthwhile to consider further research for drug development utilising the identified herbs or herb combinations. [Display omitted] [ABSTRACT FROM AUTHOR]

A disposable stochastic platform based on calix [6]arene modified multi-walled carbon nanotubes-gold nanoparticles screen-printed electrode has been developed for the simultaneous determination of calcipotriol and betamethasone. For both analytes, very wide linear concentration ranges and extremely low limits of quantification (LOQ) were obtained: from 1.0 × 10−15 to 1.0 × 10−3 mol L−1 and with a 1.0 × 10−15 mol L−1 LOQ for calcipotriol, and from 1.0 × 10−16 to 1.0 × 10−2 mol L−1 with a 1.0 × 10−16 mol L−1 LOQ for betamethasone. The applicability of the sensing platform was successfully tested in commercially available topical pharmaceutical gel and surface water samples, obtaining recovery values ranging from 99.10 to 99.99% and relative standard deviation values under 0.05%. The obtained results render the proposed platform a viable, robust, selective, and sensitive tool that can be employed for the determination of the analytes in on-site routine quality control of pharmaceuticals and water quality monitoring.

Background Randomized controlled trials (RCTs) demonstrated the advantages of an aerosol foam formulation of calcipotriol/betamethasone dipropionate (Cal/BD) in patients with psoriasis. In this review, we investigated whether such benefits could also be obtained in real-world clinical practice. Methods PubMed was searched for studies reporting real-world data in patients with psoriasis treated with Cal/BD aerosol foam. Results Three large real-world studies with Cal/BD aerosol foam were identified: a prospective non-interventional study from Germany, a medical chart review from the US, and a retrospective non-interventional study from Spain. Some key findings included the following: high levels of adherence to treatment (82–93%); after 4 weeks, about 50% of patients achieved complete/almost complete responses; at final assessment, 85–95% of patients were extremely satisfied/very satisfied/satisfied with Cal/BD aerosol foam; all healthcare providers were satisfied or somewhat satisfied with the efficacy of Cal/BD foam and they reported similar findings for symptom improvements (itch, pain, erythema/redness, flaking, and plaque thickness). Global ratings by investigators/healthcare providers for symptom control, overall efficacy and the emotional status of patients were also very high (75–100%). Conclusion The results from real-world studies undertaken in diverse healthcare systems reinforce the positive findings reported in RCTs with Cal/BD aerosol foam in patients with psoriasis.

Abstract Background Wound management is a critical factor when treating patients with the inherited skin fragility disease dystrophic epidermolysis bullosa (DEB). Due to genetic defects in structural proteins, skin and mucous epithelia are prone to blistering and chronic wounding upon minor trauma. Furthermore, these wounds are commonly associated with excessive pruritus and predispose to the development of life-threatening squamous cell carcinomas, underscoring the unmet need for new therapeutic options to improve wound healing in this patient cohort. Vitamin D3 is acknowledged to play an important role in wound healing by modulating different cellular processes that impact epidermal homeostasis and immune responses. In this study, we evaluate the safety and efficacy of low-dose calcipotriol, a vitamin D3 analogue, in promoting wound healing and reducing itch and pain in patients with DEB. Methods Eligible DEB patients, aged ≥ 6 years and with a known mutation in the COL7A1 gene, were recruited to a placebo-controlled, randomized, double blind, cross-over phase II monocentric clinical trial. Patients were required to have at least two wounds with a minimum size of 6 cm2 per wound. The primary objective was to evaluate efficacy of daily topical application of a 0.05 µg/g calcipotriol ointment in reducing wound size within a 4-week treatment regimen. Secondary objectives were to assess safety, as well as the impact of treatment on pruritus, pain, and bacterial wound colonization in these patients. Results Six patients completed the clinical trial and were included into the final analysis. Topical low-dose calcipotriol treatment led to a significant reduction in wound area at day 14 compared to placebo (88.4% vs. 65.5%, P

Background: Photoaging is mainly caused by ultraviolet radiations inasmuch they can damage the DNA, trigger ROS production, and activate p53/p21 pathway, which cause cell cycle arrest and senescence. The accumulation of senescent cells within the dermis contributes to tissue deregulation and skin carcinogenesis. However, the use of photoprotector molecules could reduce UV-induced damages and prevent photoaging. Therefore, the aim of this study is to evaluate whether the active forms of vitamin B3 (nicotinamide) and the analog of vitamin D3 (calcipotriol) might protect primary human dermal fibroblasts (HDFs) from UVB-induced photoaging. Methods: HDFs were isolated from a healthy adult donor and stimulated with nicotinamide (25 μM) and calcipotriol (100 nM) for 24h before UVB exposure, and then, cultured for further 24h on vitamin-supplemented media. Then, cell viability, ROS production, DNA damages, senescence markers, protein and gene expression were evaluated. Results: HDFs treated with nicotinamide and calcipotriol showed better proliferation properties and lower DNA damages due to a reduced UVB-induced ROS production. Consequently, p53/p21 pathway was less active which enhanced cell cycle progression and reduced senescence and cell death. Conclusions: Overall, our results suggest that nicotinamide and calcipotriol can counteract UVB-induced effects responsible for the onset of skin photoaging.