Daivobet Research Articles

Systematic analysis of serum peptidase inhibitor 3 in psoriasis diagnosis and treatment.

Psoriasis is a chronic inflammatory skin disease. To date, there are no serum biomarkers for psoriasis that have been validated to diagnose or treat psoriasis. Peptidase inhibitor 3 (PI3) levels in serum were measured using chemiluminescence immunoassay (CLIA) in two independent cohorts including healthy controls (HC) and patients diagnosed with chronic urticaria (CU), chronic eczema (CE), systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), psoriatic arthritis (PsA), or psoriasis vulgaris (PV). Receiver operating characteristic (ROC) curve analysis determined the diagnostic performance of PI3 in patients with psoriasis. The correlation between PI3 levels and the Psoriasis Area Severity Index (PASI) score was analyzed using the Spearman correlation method. Additionally, the study evaluated PI3 expression and treatment response of PV patients 12weeks before and after topical treatment with calcipotriol betamethasone and calcipotriol ointment (T#1) or topical therapy plus PSORI-CM01 granules (T#2). In cohort #1, PI3 levels effectively discriminate PV patients from HC and CU patients, with AUCs of 0.909 and 0.840, respectively. In cohort #2, AUCs for detecting PV patients among HC, CU, CE, SLE, and RA patients were 0.940, 0.926, 0.802, 0.989, and 0.951, respectively. For PsA patients, AUCs were 0.989, 0.986, 0.910, 1.000, and 0.984 compared to HC, CU, CE, SLE, and RA patients, respectively. In both cohorts, PI3 levels correlated significantly with PASI scores in PV patients (cohort #1, r = 0.433; cohort #2, r = 0.634) and PsA patients (cohort #2, r = 0.718). Moreover, univariate logistic regression analyses revealed that PV patients with higher PI3 expression had a significantly higher risk of treatment resistance, with an odds ratio of 3.45 [95% confidence interval (CI) 1.54, 7.74, p = 0.003]. Finally, PI3 levels decreased nearly 35-fold more in the responder than in the non-responder group before and after treatment. Serological PI3 is a reliable biomarker for PV diagnosis and may have the potential to predict and monitor the progression of PV before and after treatment. Key Points • This study validated PI3's diagnostic performance in two independent psoriasis cohorts using CLIA. • PI3 expression is significantly correlated with the psoriasis severity and with patients who benefited from the treatments. • Serological PI3 is a reliable biomarker for psoriasis diagnosis and may have the potential to monitor the psoriasis progression with and without treatments.

Preference for Cal/BDP Cream or Foam in Patients With Mild to Moderate Plaque Psoriasis.

The combined use of topical calcipotriol/betamethasone dipropionate (Cal/BDP) is commonly used and demonstrated to be effective for the management of psoriasis and is shown to confer local anti-inflammatory and immunoregulatory effects. The use of the two agents in combination is synergistic. Despite the demonstrated efficacy of topically applied combination Cal/BDP, successful management of a chronic, relapsing inflammatory skin disease such as psoriasis in the real-world setting may be hindered if patients do not adhere to the dosing or frequency of application recommendations from their prescriber. Patient preference for and satisfaction with the topical treatment vehicle have been shown to influence adherence. A recent analysis has determined that patients perceived Cal/BDP cream vehicle with PAD technology as having favorable characteristics. This randomized, split-body study was undertaken to further assess patient satisfaction with Cal/BDP cream and Cal/BDP foam formulations. This was a split-body, subject-blind study. Study cream was administered in a single application to one side of the scalp and/or body; study foam was applied to the contralateral side. Patient self-administered questionnaires were completed before and after product application after a single site visit. Mean overall Vehicle Preference Measure (VPM) scores were higher for Cal/BDP cream than Cal/BDP foam (P=0.0043). Cal/BDP cream also achieved higher individual scores for ease of application, feeling to the touch, smell, and feeling on the skin (P<0.03). With regards to scalp application, subject assessments show that the cream was significantly more preferred in terms of limiting daily disruption (P=0.0008) Conclusion: Results of this study suggest that patients may prefer Cal/BDP cream over Cal/BDP foam for the management of psoriasis on the body and the scalp. Cal/BDP cream outperformed Cal/BDP foam on several specific measures of satisfaction and overall satisfaction measures. J Drugs Dermatol. 2024;23(8):607-611.  doi:10.36849/JDD.7993.

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.

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

BackgroundPsoriasis 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.MethodWe 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.ResultsWe 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.ConclusionIn 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.

The role of topical therapies along the psoriasis patient journey: An overview from the Symposium 'Tailoring topical psoriasis treatments to patients' needs and expectations' of the 30th EADV Congress 2021.

This article summarizes a presentation titled 'The role of topical therapies along the psoriasis patient journey' held at the Satellite Symposium of the 30th European Academy of Dermatology and Venereology Congress. During this session, the role of topical treatments in the management of psoriasis was presented, with a particular focus on the current unmet needs and data gaps. Psoriasis plays a significant role in a patient's daily life, impacting them not only physically but also psychologically and socially. The disease burden increases with duration and severity. Topical therapies are the keystone of the management of psoriasis. About 70%-80% of patients present a mild-to-moderate form of psoriasis that can be successfully treated with topical agents. According to a German recommendation, patients with mild psoriasis should initiate a topical therapy in combination with skin care products. In the real-life setting, the calcipotriol/betamethasone dipropionate (CAL/BDP) fixed combination was the most prescribed topical treatment for beyond-mild patients in Germany, Spain and the United Kingdom. Healthcare professionals also often or very often prescribed topicals as an alternative to non-biologic systemics in certain situations, such as patient preference (51%), contraindication (50%) and to limit side effects (26%). Adjunctive topical therapy to patients using systemic therapy is used to optimize treatment outcomes and improving the quality of life for patients. Topical treatments can be also effective in severe forms of psoriasis. However, there are still some gaps and unmet needs on topical therapy. Ineffectiveness, patient dissatisfaction and adherence are the largest barriers to treatment success. Main strengths of topical treatments include the availability of various topical ingredients and galenics, the adaptability to different anatomical areas and the possible combination with phototherapy and systemics. Moreover, patients in specific situations can benefit from switching to topical treatments (e.g. pregnancy or surgery).

Real‐life self‐assessment of pruritus relief with a combination of calcipotriol/betamethasone dipropionate foam in patients with plaque psoriasis

AbstractObjectivesPsoriasis‐related pruritus is a frequent and underestimated symptom with a strong impact on quality of life, psychological condition and sleep. Our main objective was to document, in real‐life clinical practice, the perception of pruritus and the efficacy of a 4‐week topical treatment with a fixed‐dose combination of calcipotriol/betamethasone dipropionate (Cal/BD) foam on psoriasis‐related moderate‐to‐severe pruritus.MethodsThis was an exploratory prospective observational study in psoriasis patients with a pruritus visual analogic scale (VAS) score ≥ 3/10 cm. The primary endpoint was the proportion of responder patients defined as the self‐assessed improvement from baseline of pruritus of at least 2 VAS score points 48 h after the first topical administration. The quality of sleep was assessed on VAS and the quality of life was assessed using the Dermatology Life Quality Index (DLQI) on Day 28.ResultsA total of 81 patients were included by 34 dermatologists and 40 self‐questionnaires were evaluable for efficacy on Day 28. At inclusion, pruritus was self‐assessed as severe by 60.8% of patients, whereas physicians reported severe pruritus in 16.9% of patients. A proportion of 91.4% (95% confidence interval: 82–100) of patients were responders to pruritus relief 48 h after the first Cal/BD application. Relevant improvements in quality of sleep after 24 h (+2.9 ± 3.0) and in quality of life after 28 days (−9.0 ± 6.8) were reported.ConclusionThis exploratory study provides further evidence that pruritus is an underestimated symptom, and it confirms the usefulness of the fixed‐dose combination of Cal/DB foam in relieving moderate‐to‐severe pruritus and improving the quality of life and sleep in patients with plaque psoriasis.

Clinical efficacy and safety of using calcipotriol-betamethasone compounding agent for psoriasis treatment: a systematic review and meta-analysis.

The main objective is to evaluate clinical efficacy and safety of using calcipotriol-betamethasone compounding agent for psoriasis treatment through a systematic review and meta-analysis. We searched MEDLINE, Embase, The Cochrane Library, China National Knowledge Infrastructure (CNKI), China Biomedical Literature Database (CBM), and WanFang Data from inception till July 31, 2020. Efficacy was evaluated based on primary outcome indicators including skin lesion improvement and overall adverse reaction rate. Secondary outcome indicators included degree of life quality improvement, clinical effectiveness rate, and specific adverse reaction rates. RevMan5.3 was used to perform the meta-analysis. 22 studies finally met our inclusion criteria for the meta-analysis. The results indicated that for short-term treatment, a sequential therapy that uses calcipotriol betamethasone compounding agent and calcipotriol improves PASI score (MD = -0.94, 95% CI -1.38 ~ -0.49, P < 0.0001, I2 = 49%), comparing with using only calcipotriol. From a drug safety perspective, the difference in overall adverse reaction rate is not significant between the calcipotriol group and the sequential treatment group (RR = 0.50, 95% CI 0.22 ~ 1.14, P = 0.10, I2 = 33%). Calcipotriol betamethasone compounding agent may be more effective in plaque psoriasis treatment compared to use only calcipotriol, with no significant difference in adverse reaction rate between the two groups. Although the data were collected from 13 comparison groups, each group may not have sufficient data for a thorough and comprehensive analysis. Further research may be necessary for a more detailed evaluation of effectiveness of using calcipotriol betamethasone compounding agent for plaque psoriasis treatment.

Patient satisfaction with calcipotriol/betamethasone dipropionate cutaneous foam for the treatment of plaque psoriasis: The LION real-life multicenter prospective observational cohort study.

Topical treatment is the mainstay for mild or moderate psoriasis, but patients are generally little satisfied. Calcipotriol/betamethasone dipropionate (Cal/BD) cutaneous foam has shown to improve signs and symptoms in plaque psoriasis patients. This study assessed patient's satisfaction with Cal/BD foam in a real‐life Italian dermatological clinical practice. A multicenter, 4‐week observational prospective cohort study enrolled, in 17 Italian dermatology clinics, adult patients with plaque psoriasis on the body and/or scalp. Treatment satisfaction was assessed by 9‐item Treatment Satisfaction Questionnaire for Medication (TSQM‐9), preference over previous treatments by Patient Preference Questionnaire (PPQ), and change in disease state by Psoriasis Area Severity Index (PASI). Overall 256 patients were eligible, with a mean (SD) age of 55.6 (15.4) years, 59.4% were males. Psoriasis severity was mild in 52.0% of patients, moderate in 43.3%, and severe in 4.7%. Scalp involvement was present in 36.7% of patients. Previous antipsoriatic treatments had been received by 80.5% of patients. TSQM‐9 median (25th–75th percentile) scores were 83.3 (66.7–88.9) for effectiveness, 77.8 (66.7–88.9) for convenience, and 78.6 (64.3–92.9) for global satisfaction. Mean (SD) PASI value decreased from 7.3 (4.8) to 2.1 (2.7) after 4 weeks. More than 90% of patients previously treated for psoriasis evaluated the Cal/BD foam more effective, easier to use and better tolerated compared to previous topical treatments at PPQ. This observational study provides real‐life evidence of a high level of satisfaction with effectiveness and convenience of the Cal/BD foam in a cohort of plaque psoriasis patients, with an objective improvement in PASI.

Clinical, patient and estimated cost benefits of proactive management versus reactive management with calcipotriol/betamethasone dipropionate foam for the treatment of plaque psoriasis in Finland

Background Proactive management of plaque psoriasis with twice-weekly topical calcipotriol/betamethasone dipropionate (Cal/BD) foam has a demonstrated clinical benefit in preventing disease relapse compared to reactive management, where Cal/BD foam is only given as rescue therapy once-daily for four weeks after relapse. The impact of proactive management with Cal/BD foam on a wider range of clinical responses is not yet known, nor is its potential cost-effectiveness in the healthcare system of Finland. Methods This study involved a post-hoc analysis exploring the clinical and patient-reported benefits of proactive versus reactive management with Cal/BD foam observed in the PSO-LONG trial (NCT02899962). A range of response criteria based on modified psoriasis area and severity index (mPASI) and dermatology life quality index (DLQI) were analyzed, and the cost-effectiveness of proactive versus reactive management was estimated in a Finnish healthcare setting. Results and conclusion The analysis found a consistent clinical benefit of proactive management compared to reactive management on all response criteria, and a markedly lower cost-per-responder for the response criteria of mPASI 75, mPASI ≤ 2 and DLQ1 ≤ 1. The analysis was robust to sensitivity analyses on key inputs and demonstrates the cost and clinical benefits of proactive over reactive management of plaque psoriasis with Cal/BD foam in the Finnish healthcare setting.

Calcipotriol/Betamethasone Dipropionate Aerosol Foam for Plaque Psoriasis: A Prospective, Observational, Non-Interventional, Single-Center Study of Patient Adherence and Satisfaction in Daily Use.

Psoriasis is a chronic inflammatory disease that has a negative impact on patients' quality of life. Patients with mild-moderate psoriasis can be treated with topical medications, such as the combination drug calcipotriol/betamethasone dipropionate (Cal/BD). This study investigated the adherence of psoriasis patients to therapy with Cal/BD aerosol foam, as well as their satisfaction with the treatment's efficacy, safety, and effect on their quality of life. Patients with mild-moderate plaque psoriasis were eligible to participate in this open-label, non-placebo controlled, prospective single-center study. Adherence to treatment was assessed using the Morisky-Green scale 4 and 12 weeks after the start of treatment. Satisfaction with the treatment was assessed using the abbreviated Treatment Satisfaction Questionnaire for Medication (TSQM-9). The severity of psoriasis was assessed on the mIGA and PGA scales, and the impact on quality of life was assessed using the PDI and DLQI scales. A total of 65 patients entered the study. Adherence to treatment was good, with 73.8% of patients showing high adherence at 12 weeks. Satisfaction was also good, with 46 patients (70.8%) being completely satisfied. Over a 4-week period, patients treated with Cal/BD aerosol foam had significant improvement in disease severity that was directly related to treatment adherence.

The Effect on BSA of Proactive Management versus Reactive Management of Psoriasis With Fixed-Dose Cal/BD Foam in the PSO-LONG Study.

Reduction of psoriasis body surface area (BSA) is associated with improved patient quality of life. Post-hoc analyses of the PSO-LONG study compared impact on BSA of proactive management versus reactive management strategies using calcipotriol/betamethasone dipropionate (Cal/BD) foam. Mean BSA values, as well as normalized area under the curves (AUCs) for patient BSA were assessed. Analyses found that after the PSO-LONG study&rsquo;s four-week open-label lead-in phase, when all patients received once-daily Cal/BD foam, mean BSA was significantly reduced. Thereafter, mean BSA remained at lower levels in patients on proactive management compared to reactive management. This was reflected in AUC BSA, which was consistently lower in the proactive management arm. Treatment-related differences were statistically significant when analyzing the full analysis set (FAS) population, as well as when restricting the analysis to study completers. Additional analyses restricted the dataset to include only observations from psoriasis remission periods, or periods of disease relapse. Treatment-related differences in AUC were statistically significant in observations during remission, but not during relapse. This could be expected given the trial&rsquo;s design, wherein all patients who relapsed were offered the same rescue therapy with once daily Cal/BD foam. Similarly, for patients who dropped out, there was no treatment-related difference in mean BSA during the two weeks preceding dropout, likely due to the common occurrence of relapse in these patients. This paper found that proactive management, in addition to preventing more relapses as previously shown, also maintained BSA at a lower level during remission than reactive management. J Drugs Dermatol. 20(5):567-570. doi:10.36849/JDD.5870.

EVALUATION OF EFFICACY AND SAFETY OF TOPICAL NICOTINAMIDE FOR TREATMENT OF PSORIASIS VERSUS CALCIPOTRIOL-BETAMETHASONE: COMPARATIVE STUDY

Background: Psoriasis is a chronic skin disorder typically characterized by symmetrical erythematous papules and plaques with a silver scale. Objective: To compare the efficacy and safety of topical nicotinamide for the treatment of mild to moderate psoriasis in Interventional Clinical Trial study compared with calcipotriol-betamethasone. Patients and methods: Our study was carried out on sixty patients from November 2019 to March 2020, complaining of psoriasis thirty patients treated by topical nicotinamide 4% weekly and thirty patients treated by topical calcipotriol-betamethasone weekly. Patients were selected from out-patient clinic of Dermatology, Venereology and Andrology Department of Al-Azhar University Hospitals. Results: The present study using topical nicotinamide 4% weekly versus calcipotriol –betamethasone weekly showed lesions on both sides were similar regarding baseline Psoriasis Area and Severity Index (PASI) score (P = 0.148), while at 1 month and 3 months after therapy, PASI scores were significantly lower with calcipotriol betamethasone in the second group as compared with nicotinamide alone in first group (P < 0.001). At the end of the trial, PASI scores were reduced by 17.9± 7.8 points before treatment to 12.2± 5.08 after 12 weeks with nicotinamide as compared to 16.2 ± 5.5 before treatment to 9.1± 3.2 points with calcipotriol betamethasone (P < 0.001). Conclusion: Nicotinamide can be used for topical psoriasis treatment and may be a good adjuvant to be added to the treatment regimens of psoriasis and it was less effective than calcipotriol betamethasone regarding clinical response and patient's satisfaction.

Efficacy of topical calcipotriol betamethasone dipropionate as a new adjuvant therapy to follicular unit extraction technique in treatment of stable vitiligo: clinical, dermoscopic and immunohistological study.

Follicular unit extraction (FUE) grafting is a surgical procedure which provides the vitiliginous patches with undifferentiated stem cells of the hair follicles. It has been postulated that adjuvant therapy enhances the results. This is the first study to assess two different adjuvant therapies vs FUE alone. To study the efficiency of FUE alone or combined with either topical calcipotriol betamethasone dipropionate (CBD) or NB-UVB phototherapy in cases of nonsegmental stable vitiligo. To assess the role of dermoscopy in monitoring the pattern and degree of repigmentation. 53 patients with 94 lesions with stable nonsegmental vitiligo were divided into three groups. Group 1 (n=16) with 30 lesions received FUE alone. Group 2 (n=18) with 32 lesions received FUE plus topical CBD. Group 3 (n=19) with 32 lesions received FUE plus NB-UVB phototherapy. Assessment was done by grades of repigmentation, color match, percent of size reduction, and immunohistochemical evaluation of perilesional CD8+T lymphocytes. The fastest onset of repigmentation was observed in both groups 2 and 3 in the second week (16.7%, 10.5%, respectively).Group 2 achieved the best response by all methods of assessment. Perifollicular diffuse repigmentation was the commonest dermoscopic pattern in 60 lesions (63.8%). There was a statistically significant decrease in perilesional CD8+T lymphocytes after 4months. FUE is an effective method of surgical treatment of stable vitiligo, and topical CBD as a new adjuvant therapy is successful in targeting the immunological background of vitiligo. Dermoscopy has an essential role in monitoring the repigmentation response.

Calcipotriol/Betamethasone Dipropionate Foam Inhibits Th17 Cytokine Secretion and Improves Epidermal Barrier Markers in a Human Th17 Skin Inflammation Model.

IntroductionT-helper 17 (Th17) cytokines play a key role in the pathophysiology of psoriasis by driving inflammatory responses that lead to epidermal alterations. Markers of epidermal differentiation, including the proteins loricrin (LOR), filaggrin (FLG) and involucrin (IVL), are dysregulated in psoriatic skin. The fixed-dose combination of calcipotriol/betamethasone dipropionate (Cal/BD) foam and clobetasol propionate (CP) are widely used, effective topical treatments for psoriasis. In this study, we investigated the effects of Cal/BD foam and CP cream on Th17 cytokine secretion and epidermal differentiation using a human Th17 skin inflammation model (InflammaSkin®).MethodsThe fixed-dose combination Cal/BD foam and the CP cream were applied once and twice daily, respectively, onto the air-exposed epidermal surface of InflammaSkin cultures for 7 days. Th17 cytokine levels were measured in culture supernatants, and gene expression analysis and immunohistochemical staining for LOR, FLG and IVL were performed on the skin samples.ResultsTopical treatment with Cal/BD foam almost completely inhibited Th17 cytokine secretion and upregulated LOR and IVL expression, but not FLG expression, at the mRNA and protein levels. Topical treatment with CP cream significantly reduced Th17 cytokine levels, but to a lesser extent than Cal/BD foam, and did not improve expression of any of the epidermal differentiation markers.ConclusionCompared with CP treatment, the fixed-dose combination Cal/BD foam showed a greater suppression of Th17 cytokine secretion and improved epidermal differentiation, resulting in an overall higher degree of improvement of the skin. These results support our understanding of the mechanisms behind the clinical efficacy observed for Cal/BD foam and of its use for long-term proactive treatment of psoriasis vulgaris.

PGAxBSA composite versus PASI: Comparison across disease severities and as therapeutic response measure for Cal/BD foam in plaque psoriasis

Theproduct of the Physician Global Assessment and body surface area (PGA×BSA) is simpler to use than the Psoriasis Area and Severity Index (PASI), which lacks sensitivity in patients with mild psoriasis. To compare the PGA×BSA versus the modified PASI (mPASI) for assessing disease severity and therapeutic response to calcipotriol/betamethasone dipropionate (Cal/BD) foam. This post hoc analysis evaluated the efficacy of Cal/BD foam in mild, moderate, and severe psoriasis, as assessed by the PGA×BSA and mPASI, using data from 3 randomized controlled trials (NCT01536886, NCT01866163, NCT02132936). Spearman correlation and Bland-Altman plots were used to compare the PGA×BSA with the mPASI. Proportions of patients receiving Cal/BD foam achieving 75% response for PGA×BSA and mPASI at weeks 1, 2, and 4 were similar and significantly greater than with vehicle (P≤.002 at all timepoints); at week 4, mean improvements were 51.0% and 50.7%, respectively. Spearman correlations for mild, moderate, and severe psoriasis were moderate to high between PGA×BSA and mPASI at baseline (r=.51, .72, and .86, respectively; n= 126, 465, and 58, respectively) and high at week 4 (r=.80, .81, and .89, respectively; n=121, 452, and 58, respectively) (P<.001). Pooled data from different trials were not prespecified for post hoc analysis. Interrater reliability was not assessed. Pooled data analysis showed that the PGA×BSA and mPASI correlation was higher with increasing psoriasis severity.

Cost per PASI-75 responder of calcipotriol plus betamethasone dipropionate cutaneous foam versus nonbiologic systemic therapies for the treatment of plaque psoriasis in seven European countries

Purpose To compare the short-term cost and effectiveness of calcipotriol/betamethasone dipropionate (Cal/BD) cutaneous foam against nonbiologic systemics in psoriasis patients for whom oral systemic or topical therapy is considered appropriate in seven European countries. Methods Matching-adjusted indirect comparisons of four-week PASI-75 responses of Cal/BD foam were performed versus 12-week responses of methotrexate, acitretin, fumaric acid esters (FAE) and 16-week responses of apremilast. Analyses took a payer perspective and included drug, physician visit and monitoring costs. Results In all countries, Cal/BD foam generated the lowest cost per responder (CPR). Against methotrexate, apremilast and acitretin, Cal/BD foam generated response for less than €190 in Italy, €195 in Portugal, €216 in Greece, £218 in the United Kingdom, €250 in Belgium, €319 in Spain, and €359 in the Netherlands. Relative to treatment with FAE, Cal/BD foam resulted in response for less than €298, €430, €382 and £262 in Belgium, the Netherlands, Spain and the United Kingdom, respectively. For Cal/BD foam, apremilast and FAE, total costs were driven by drug costs; for methotrexate and acitretin, by monitoring. Conclusions Driven by its lower costs and high response rates, Cal/BD foam is likely to be a cost-effective option over the short-term in the investigated psoriasis population.

Calcipotriol/betamethasone dipropionate aerosol foam for the treatment of psoriasis vulgaris: a review of real-world evidence (RWE)

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.

Auricular acupressure as a complementary therapy for psoriasis vulgaris: study protocol for a multicenter randomized controlled trial

IntroductionPsoriasis vulgaris is a common skin disease characterized by persistent localized erythematous scaly plaques, typically on the elbows, knees, and scalp. It is an immune-abnormal disease that progresses slowly over a long period with frequent symptom recurrence. Current studies have shown that acupuncture is an effective therapy for psoriasis. However, the scientific evidence of the efficacy of auricular acupressure treatment for patients with psoriasis is still insufficient. Therefore, we designed a randomized controlled clinical trial to investigate the effect, safety, and cost-effectiveness of auricular acupressure in addition to medication in patients with psoriasis.Methods and analysisThis on-going study is a two-arm parallel, assessor-blinded, randomized controlled trial in which 180 participants with psoriasis will be recruited and then randomly allocated into two groups in a 1:1 ratio. Equal randomization will be conducted using a computer-generated random allocation sequence. Participants in the intervention group will receive auricular acupressure treatment once per week for 4 weeks, and calcipotriol betamethasone ointment for topical use once daily for 4 weeks. Participants in the control group will receive only calcipotriol betamethasone ointment treatment once daily for 4 weeks. All patients will be followed up for 12 weeks. The primary outcome is relapse rate. The secondary outcomes include time to relapse, rebound rate, time to new onset, Psoriasis Area and Severity Index score improvement rate, body surface area affected, a visual analogue scale, and Dermatology Life Quality Index. Cost-effectiveness analysis will be carried out from a health and community care provider perspective.DiscussionThis multicenter randomized controlled trial will provide important clinical evidence for the effect and safety of auricular acupressure as a complementary therapy in patients with psoriasis.Trial registrationChinese Clinical Trial Registry, ChiCTR-TRC-14004916. Registered on 20 May 2014. This protocol is version 3.0 which was updated on 24 September 2016.

Low systemic exposure and calcemic effect of calcipotriol/betamethasone ointment in rats with imiquimod-induced psoriasis-like dermatitis

Vitamin D3 (VD3) analogues-containing ointments are known to occasionally cause hypercalcemia in psoriasis patients, and the frequency of hypercalcemia is suggested to vary based on the VD3 analogue used. In this study, to address the differences in calcemic effects of VD3-containing ointments, the calcemic effects of marketed VD3-containing ointments, including calcipotriol (Cal), maxacalcitol (Max), tacalcitol (Tac), calcipotriol/betamethasone dipropionate (Cal/BDP) and maxacalcitol/betamethasone butyrate propionate (Max/BBP) ointments, were evaluated in a rat model of imiquimod-induced dermatitis. The topical application of Tac, Max and Max/BBP ointments, but not Cal and Cal/BDP ointments, to the imiquimod-induced skin lesions significantly induced an increase in the serum calcium level compared with the vaseline-treated group. Calcemic effect of VD3 analogues in rats treated with VD3-containing ointments was analyzed by evaluating the expression of vitamin D receptor target genes, such as Cyp24a1, Trpv5 and CalbindinD28k, in the intestine and kidney. Real-time reverse transcription PCR (RT-PCR) analysis showed that the renal and intestinal Cyp24a1 expressions in the Cal- and Cal/BDP-treated groups were significantly lower than those in the Tac-, Max- and Max/BBP-treated groups, suggesting that systemic exposure of VD3 analogues in the Cal- and Cal/BDP-treated groups were lower than those in the other ointment-treated groups. In addition, the renal Trpv5 and CalbindinD28k expressions, calcium-transporting genes, were increased in the Max- and Max/BBP-treated groups compared with the Cal- and Cal/BDP-treated groups. Thus, because of the low systemic exposure of VD3 analogues, Cal and Cal/BDP ointments have lower calcemic effect than the other VD3-containing ointments in rats with psoriasis-like dermatitis.

Noninvasive proteome analysis of psoriatic stratum corneum reflects pathophysiological pathways and is useful for drug profiling.

Protein expression is disturbed in the psoriatic stratum corneum (SC). Noninvasive methods for the description of pathophysiological changes and drug profiling in psoriasis are desirable. Undertake large-scale noninvasive protein expression studies in psoriatic SC to identify biomarkers of pathophysiological processes and use them for drug profiling. Psoriatic SC was harvested through repetitive tape-stripping. Nonlesional and lesional SC, as well as vehicle-treated and drug-treated lesional SC samples were collected. Protein extracts from nonlesional and lesional skin biopsies were used for comparison. Calcipotriol-betamethasone (CB) was used as a reference medication. Proteins extracted from pooled tape strips were quantified using mass spectrometry (MS), Western blotting, enzyme-linked immunosorbent assay and Luminex technologies. MS-based methods identified 140 proteins differentially expressed in psoriatic SC. Epidermis development, glycolysis, regulation of apoptosis, cytoskeleton organization and peptide cross-linking were modulated, all reflecting perturbed epidermal differentiation. Using antibody-based techniques, increased levels of sICAM1, of CXCL1- and CXCL8-attracting neutrophils, of CXCL10- and CCL4-attracting T helper (Th) 1 cells, and of CCL2- and CCL4-attracting monocytes and dendritic cells were observed. Quantification of the Th1 and Th17 markers tumour necrosis factor, interleukin (IL) 12B, IL17A and IL17F in lesional SC was successful, while the Th2 cytokines IL4, IL5 and IL13, not involved in the disease process, were not detected. The pruritic cytokine IL31 was detected in lesional SC. CXCL1, CXCL8, CXCL10 and sICAM were used to investigate disease remission, ranking three topical treatments according to their known clinical efficacy. Protein biomarker quantification in psoriatic SC detects key pathophysiological mechanisms and enables noninvasive drug profiling in translational medicine settings.