A Comparative Study of the Effectiveness and Safety of Topical Calcipotriol and Topical Methotrexate in Chronic Plaque Psoriasis.

Background Psoriasis is a papulosquamous disease with variable morphology, distribution, severity, and course. Chronic plaque psoriasis, or psoriasis vulgaris, is the most common form of psoriasis. Present available preparations for mild to moderate chronic plaque psoriasis for topical use are local corticosteroids, coal tar, dithranol, tazarotene, calcipotriol, tapinarof, and calcineurin inhibitors. However, every preparation has its disadvantages. Calcipotriol, an active form of vitamin D, is available in topical form for dermatological use. Chronic plaque psoriasis is the chief medical use of calcipotriol for mild to moderate form. Methotrexate has dramatic results in psoriasis when used systemically. Now, topical formulation is being advocated in localized psoriasis, which is not associated with the side effects of the systemic form. Therefore, this study aimed to compare the effectiveness of topical calcipotriol and topical methotrexate on the basis of the psoriasis area severity index (PASI) in patients of chronic plaque psoriasis and compare their safety in terms of adverse effects. Methodology The total number of patients included in the study was 60. They were divided into two groups, with 30 patients each. One group was prescribed ointment calcipotriol 0.005% twice daily local application (Group C). The other group was prescribed methotrexate gel 1% twice daily local application (Group M). The patients were followed up on the fourth and eighth weeks, and at each time, thorough clinical examinations were conducted for all patients. The PASI score was calculated in each patient every time. Safety was assessed by biochemical parameters, and tolerability was assessed by the incidence of adverse effects. All the patients included in the study were investigated at baseline, fourth week, and eighth week. The data collected were transferred to a master chart and analyzed. Results For the patients in group C, the mean PASI score at 0 week was 5.93 ± 2.62, while at four weeks, the mean PASI score declined to 1.67 ± 1.13, and at eight weeks, the mean PASI score further declined to 0.67 ± 0.68. For the patients in group M, the mean PASI score at 0 week was 5.91 ± 2.22, while at four weeks, the mean PASI score declined to 1.91 ± 1.11, and at eight weeks, the mean PASI score further declined to 0.89 ± 0.72. Furthermore, there was no significant difference in the mean PASI score at various time points when compared between the two groups (p-value = 0.761, 0.296, 0.079, respectively). Thus, both drugs seem to be effective in treating mild- to moderate-grade chronic plaque psoriasis. Most of the patients in both groups showed marked clearance of the lesions. However, there were six patients in the calcipotriol group showing complete clearance of the lesions having mild-degree plaque psoriasis, as compared to three patients in the methotrexate group. In the present study, based on the comparison of safety and tolerability, four out of 30 patients (13.3%) in the calcipotriol group suffered skin irritation, whereas six out of 30 patients (20%) in the methotrexate group complained of a burning sensation. The adverse effects seen in the patients were transient and mild. Conclusion Topical calcipotriol and methotrexate were effective in reducing lesions in patients with chronic mild to moderate plaque psoriasis. Both drugs were well tolerated with mild and transient adverse effects and did not alter hematological and biochemical parameters.

Calcipotriol Nanosuspension-Loaded Trilayer Dissolving Microneedle Patches for the Treatment of Psoriasis: In Vitro Delivery and In Vivo Antipsoriatic Activity Studies.

Psoriasis, affecting 2-3% of the global population, is a chronic inflammatory skin condition without a definitive cure. Current treatments focus on managing symptoms. Recognizing the need for innovative drug delivery methods to enhance patient adherence, this study explores a new approach using calcipotriol monohydrate (CPM), a primary topical treatment for psoriasis. Despite its effectiveness, CPM's therapeutic potential is often limited by factors like the greasiness of topical applications, poor skin permeability, low skin retention, and lack of controlled delivery. To overcome these challenges, the study introduces CPM in the form of nanosuspensions (NSs), characterized by an average particle size of 211 ± 2 nm. These CPM NSs are then incorporated into a trilayer dissolving microneedle patch (MAP) made from poly(vinylpyrrolidone) and w poly(vinyl alcohol) as needle arrays and prefrom 3D printed polylactic acid backing layer. This MAP features rapidly dissolving tips and exhibits good mechanical properties and insertion capability with delivery efficiency compared to the conventional Daivonex ointment. The effectiveness of this novel MAP was tested on Sprague-Dawley rats with imiquimod-induced psoriasis, demonstrating efficacy comparable to the marketed ointment. This innovative trilayer dissolving MAP represents a promising new local delivery system for calcipotriol, potentially revolutionizing psoriasis treatment by enhancing drug delivery and patient compliance.

Targeting LRP6: A new strategy for cancer therapy.

Targeting specific molecular drivers of tumor growth is a key approach in cancer therapy. Among these targets, the low-density lipoprotein receptor-related protein 6 (LRP6), a vital component of the Wnt signaling pathway, has emerged as an intriguing candidate. As a cell-surface receptor and vital co-receptor, LRP6 is frequently overexpressed in various cancer types, implicating its pivotal role in driving tumor progression. The pursuit of LRP6 as a target for cancer treatment has gained substantial traction, offering a promising avenue for therapeutic intervention. Here, this comprehensive review explores recent breakthroughs in our understanding of LRP6's functions and underlying molecular mechanisms, providing a profound discussion of its involvement in cancer pathogenesis and drug resistance. Importantly, we go beyond discussing LRP6's role in cancer by discussing diverse potential therapeutic approaches targeting this enigmatic protein. These approaches encompass a wide spectrum, including pharmacological agents, natural compounds, non-coding RNAs, epigenetic factors, proteins, and peptides that modulate LRP6 expression or disrupt its interactions. In addition, also discussed the challenges associated with developing LRP6 inhibitors and their advantages over Wnt inhibitors, as well as the drugs that have entered phase II clinical trials. By shedding light on these innovative strategies, we aim to underscore LRP6's significance as a valuable and multifaceted target for cancer treatment, igniting enthusiasm for further research and facilitating translation into clinical applications.

Effectiveness of calcipotriol/betamethasone dipropionate aerosol foam in patients with small versus large plaque psoriasis in routine practice in South Korea.

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.

Real-world use, perception, satisfaction, and adherence of calcipotriol and betamethasone dipropionate PAD-cream in patients with plaque psoriasis in Spain and Germany: results from a cross-sectional, online survey.

BACKGROUND: Psoriasis significantly impacts patients' quality of life (QoL). Dissatisfaction and non-adherence are major barriers associated with topical treatments. A cream based on the polyaphron dispersion (PAD) Technology containing a fixed-dose of calcipotriol (CAL) and betamethasone dipropionate (BDP) was designed for a patient-friendly psoriasis management. The CAL/BDP PAD-cream demonstrated efficacy, convenience, and safety/tolerability in clinical trials. OBJECTIVES: This research assesses the real-world use, perception, satisfaction, and adherence of CAL/BDP PAD-cream among plaque psoriasis patients. METHODS: Between September-November 2023, psoriasis patients from Spain and Germany using or having used CAL/BDP PAD-cream for >2 weeks were recruited via Wefight network to complete a 30-questions online survey. Anonymized results were pooled for descriptive statistical analysis. RESULTS: The survey was completed by 129 patients (mean age: 43 years; 66% females; mean psoriasis duration: 12 years). Most patients (93%) were satisfied with CAL/BDP PAD-cream. The 66% reported high adherence (visual analogue scale 80-100) and 91% preferred CAL/BDP PAD-cream to their previous topical(s). Patients highlighted its ease/convenience of application, tolerability, and lack of itching/burning. CONCLUSIONS: Psoriasis patients treated with CAL/BDP PAD-cream in a real-world setting show high satisfaction, good adherence, and a positive perception of the product, suggesting that favorable outcomes observed in clinical trials translate to real clinical practice.

A narrative review of fixed combination calcipotriol/betamethasone aerosol foam (Enstilar®) in the management of psoriasis with scalp involvement.

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.

Topical Calcipotriol Plus 5-Fluorouracil in the Treatment of Actinic Keratosis, Bowen's Disease, and Squamous Cell Carcinoma: A Systematic Review.

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.

Clinical efficacy observation of calcipotriol combined with AYJ sodium alginate repair dressing in the treatment of psoriasis vulgaris and its effect on patients' neurological function.

OBJECTIVE: To 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Chinese herbal medicine bath therapy for psoriasis vulgaris using topical calcipotriol as the comparator: A systematic review with meta-analysis and association rule analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: 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. AIM OF THE STUDY: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

A Prospective, Multicenter, Open-label Study to Evaluate the Safety and Efficacy of a Cream Containing Xyloglucan, Pea Protein, and Opuntia ficus-indica Extract Versus Calcipotriol/Betamethasone in Adult Patients with Mild-to-moderate Psoriasis.

Objective: Psoriasis is a chronic, inflammatory skin disease, requiring local and systemic drugs according to disease severity. This study aims to investigate the efficacy and safety of a topical treatment containing xyloglucan, pea proteins and Opuntia ficus-indica extracts (XPO) compared to calcipotriol 50mcg/betamethasone 0.5mg ointment (CB). Methods: Forty-two patients diagnosed with mild-to-moderate plaque psoriasis were assigned 1:1 to XPO treatment or CB for 28 days. Disease status was assessed at baseline (V1), monitored every two weeks (V2, V3), and at follow-up (V4). Disease severity was assessed by PASI (Psoriasis Area and Severity Index), PGA (Physician's Global Assessment), and VAS (Visual Analog Scale for itching). Photos were taken before and after XPO treatment. Treatment efficacy was determined by comparing psoriasis severity at baseline to V3. Tolerability was assessed by monitoring the occurrence of adverse events. Results: Both groups showed a statistically significant difference in PASI score from V1 to V2 (p=0.001, XPO; p=0.008, CB) and to V3 (p=0.001, XPO; p=0.004, CB). XPO achieved a PASI 50 score of 24 percent at V2 and 52 percent at V3 compared to CB (0% at V2 and 19% at V3). At V3, PGA was significantly reduced in both groups (p=0.003, XPO; p=0.001 CB). Both treatments significantly reduced itching at V2 (p=0.001, XPO; p=0.003, CB) and V3 (p=0.001, XPO; p=0.0005, CB). Conclusion: XPO showed similar efficacy to CB, significantly reducing disease severity, erythema, itching, induration, and scaling with an excellent tolerability profile.

Improvements in Plaque Psoriasis Associated with Calcipotriol/Betamethasone Aerosol Foam Treatment: A Post Hoc Analysis of Non-interventional Studies and Clinical Experience.

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.

The Management of Plaque Psoriasis With Halobetasol and Tacrolimus Combination Therapy Versus Calcipotriol Monotherapy: A Case Report.

Psoriasis is an inflammatory, immune-mediated, persistent, and multifactorial skin disease. Chronic plaque psoriasis is the most common clinical form of psoriasis. Pro-inflammatory cytokines play a primary role in the pathogenicity of this disease. Psoriasis is mainly diagnosed using clinical and dermoscopic examination of the cutaneous lesions, and skin biopsy is used in atypical cases. Psoriasis has no definitive cure. However, several topical agents are effective in managing mild and chronic cases. Combination therapy with these topical agents is more effective than with a single agent. We report a case of chronic plaque psoriasis in a 33-year-old man presenting with an itchy circumscribed, erythematous, scaly plaque, and a single cutaneous lesion covering >50% of both forearms and a few lesions on the back. The right forearm was treated with calcipotriol alone, whereas the left forearm was treated with a tacrolimus and halobetasol combination with emollients to be applied twice a day on both arms. We observed treatment responses for seven days with 24-hour intervals after each application. Combination therapy yielded a better response. In conclusion, topical treatment with a combination of halobetasol and tacrolimus is more effective compared to that with a single agent while being cost-effective and causing minimal adverse effects.

1% Tapinarof cream for the treatment of psoriasis: a network meta-analysis of randomized placebo- and calcipotriol- controlled trials.

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.

Calcipotriol suppresses GPX4-mediated ferroptosis in OA chondrocytes by blocking the TGF-ß1 pathway.

Globally, tens of millions of individuals experience osteoarthritis (OA), a degenerative joint condition for which a definitive cure is currently lacking. This condition is characterized by joint inflammation and the progressive deterioration of articular cartilage. In this study, western blotting, quantitative reverse-transcription polymerase chain reaction, and immunofluorescence analysis were performed to elucidate the molecular mechanisms by which calcipotriol alleviates chondrocyte ferroptosis. The effect of calcipotriol on reactive oxygen species and lipid peroxidation levels in chondrocytes was assessed using dihydroethidium staining and the fluorescent dye BODIPY. To replicate OA, the destabilized medial meniscus model was employed, followed by the injection of calcipotriol into the knee articular cavity. Morphological analysis was conducted through hematoxylin and eosin staining, safranin O-Fast green staining, and micro-computed tomography analysis. Immunohistochemical analysis was performed to validate the effect of calcipotriol in vivo. Our results demonstrate that the expression of SOX9, col2a1, and Aggrecan, as well as MMP13 and ADAMTS5 protein expression levels, decrease upon treatment with calcipotriol in interleukin-1ß stimulated chondrocytes. Despite these promising outcomes, the exact mechanism underlying calcipotriol's therapeutic effect on OA remains uncertain. We discovered that calcipotriol inhibits chondrocyte GPX4-mediated ferroptosis by suppressing the expression of transforming growth factor-ß1. Furthermore, our study established an in vivo model of OA using rats with medial meniscus instability. Our experiments on rats with OA revealed that intra-articular calcipotriol injection significantly reduces cartilage degradation caused by the disease. Our findings suggest that calcipotriol can mitigate OA by impeding GPX4-mediated ferroptosis of chondrocytes, achieved through the suppression of the TGF-ß1 pathway.

Calcipotriol and Betamethasone Dipropionate Cream Based on PAD Technology for the Treatment of Plaque Psoriasis: A Narrative Review.

Topical treatment plays a crucial role in psoriasis management, with non-adherence being a major barrier to treatment success. The fixed-dose combination of calcipotriol (CAL) and betamethasone dipropionate (BDP) represents the first-line choice in topical psoriasis treatment. A CAL/BDP cream based on polyaphron dispersion (PAD) Technology has emerged as a novel formulation for a more convenient topical treatment of psoriasis. This article aims to summarize the most relevant published evidence about CAL/BDP PAD-cream and its underlying PAD Technology. The PAD Technology enables CAL and BDP stability in an aqueous cream through a multimolecular shell structure, as well as it increases the penetration of both active ingredients into the epidermis and dermis. This technology also demonstrated to increase the cosmetic acceptability and to provide the desirable sensory properties for a topical psoriasis treatment. Two phase III clinical trials have been conducted so far with CAL/BDP PAD-cream. Findings from both trials revealed high efficacy with a fast onset of action, a favourable safety and tolerability profile and convenience for CAL/BDP PAD-cream compared to CAL/BDP gel. In the trial including patients with psoriasis affecting the scalp (MC2-01-C7), results support the use of CAL/BDP PAD-cream in scalp psoriasis. An anchored matching-adjusted indirect comparison (MAIC) was conducted to compare CAL/BDP PAD-cream and CAL/BDP foam, as both products had been previously compared to CAL/BDP gel. CAL/BDP PAD-cream and CAL/BDP foam showed equivalent efficacy and quality of life at their recommended treatment duration, whereas greater treatment satisfaction for CAL/BDP PAD-cream was found after one week of treatment. Overall, the high patient acceptability and treatment satisfaction observed with CAL/BDP PAD-cream in clinical trials may lead to improved adherence and hence higher efficacy in clinical practice.

Nano-calcipotriol as a potent anti-hepatic fibrosis agent.

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.

Potential biomarkers for psoriasis topical treatment by in-depth serum proteomics.

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 < 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. CONCLUSION: 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.

Comparison of the efficacy of tacrolimus 0.1% ointment vs calcipotriol/betamethasone in combination with NBUVB in treatment of vitiligo.

Purpose: Vitiligo is an idiopathic depigmenting skin disorder. The study compares the efficacy of topical tacrolimus 0.1% with calcipotriol/betamethasone dipropionate in vitiligo patients receiving NB-UVB treatment.Materials and methods: Forty-one adult patients with generalized type vitiligo were recruited. Patients were assigned to phototherapy and then classified into either group one (20 patients), receiving calcipotriol/betamethasone dipropionate cream (D group), or group two (21 patients), receiving tacrolimus 0.1% ointment (T group). They were followed-up at 3 and 6 months.Results: The D group witnessed an increase in the repigmentation area from 35.4% in the third month to 54.7% in the sixth month (p = 0.001) and the T group from 32.2% to 45.6% (p = 0.011). However, the differences between the treatment groups were not statistically significant. Body sites demonstrated different levels of improvement ranging from the highest in the face to the lowest in the Hand & Feet with the other body sites in between. A negative correlation was identified between the duration since diagnosis and the response to D treatment (3 months: r = -0.612, p = 0.007; 6 months: r = -0.755, p = 0.001).Conclusions: Although both combinations are efficacious, they did not significantly differ in efficacy at three and six months follow-up points.Clinical trial registration: The study was registered at clinicaltrials.gov (NCT04440371).

Vitamin D3 analogue calcipotriol inhibits the profibrotic effects of transforming growth factor- ß1 on pancreatic stellate cells.

OBJECTIVE: To evaluate the inhibitory effect of vitamin D3 analogue calcipotriol (Cal) on the fibrosis of pancreatic stellate cells (PSCs) induced by TGF-ß1 and the rationality of Cal use in alcoholic chronic pancreatitis (ACP). MATERIAL AND METHODS: Double-labeling immunofluorescence was used for the identification of VDR+PSCs in the pancreas of healthy controls (HC) and ACP patients. Van Gieson staining for examination of collagen fibers. RT-qPCR and Western Blot for determining the mRNAs and proteins of VDR, TGF-ß1 and COL1A1 in the pancreas of ACP or in vitro PSCs. ELISA or LC-MS/MS for detection of serum TGF-ß1 and COL1A1 or 25(OH)D3. The PSC line (RP-2 cell) was used for the determination of proteomic alterations in Cal plus TGF-ß1 versus TGF-ß1 and to examine the effect of VDR gene knockdown. RESULTS: Enhanced expression of VDR was detected in RP-2 cells stimulated with alcohol (ALC) plus Cal versus Cal alone and in PSCs in the pancreas of ACP versus HC. The increased VDR+PSCs were positively correlated with the levels of COL1A1 mRNAs or areas of collagen deposition in the pancreas of ACP. TGF-ß1 was overexpressed in the pancreas of ACP and ALC-treated RP-2 cells while 25(OH)D3 level in serum was significantly decreased in ACP versus HC. Through a VDR-dependent mechanism, Cal antagonized 16 profibrotic proteins in TGF-ß1-induced RP-2 cells that included 7 extracellular matrix components, 2 cytoskeletal proteins, 2 fibrosis-associated factors (RUNX1 and TRAF2), TIMP-1, CCN1, integrin α11, an adhesion scaffold protein (TGFB1i1) and an enzyme mediating TGF-ß1-induced fibrogenesis (ENPP1). CONCLUSION: This study suggests that Cal administration may be a potential antifibrotic strategy via inhibiting TGF-ß1-mediated PSC action during the development of ACP.

A nanodrug simultaneously inhibits pancreatic stellate cell activation and regulatory T cell infiltration to promote the immunotherapy of pancreatic cancer.

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. STATEMENT OF SIGNIFICANCE: 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.