Cocktail of Ropivacaine, Morphine, and Diprospan Reduces Pain and Prolongs Analgesic Effects after Total Knee Arthroplasty: A Prospective Randomized Controlled Trial.

Background: Local infiltration analgesia (LIA) provides postoperative analgesia for total knee arthroplasty (TKA). The purpose of this study was to evaluate the analgesic effect of a cocktail of ropivacaine, morphine, and Diprospan for TKA. Methods: A total of 100 patients from September 2018 to February 2019 were randomized into 2 groups. Group A (control group, 50 patients) received LIA of ropivacaine alone (80 ml, 0.25% ropivacaine). Group B (LIA group, 50 patients) received an LIA cocktail of ropivacaine, morphine, and Diprospan (80 ml, 0.25% ropivacaine, 0.125 mg/ml morphine, and 62.5 µg/ml compound betamethasone). The primary outcomes were the levels of inflammatory markers C-reactive protein (CRP) and interleukin-6 (IL-6), pain visual analog scale (VAS) scores, opioid consumption, range of motion (ROM), functional tests, and sleeping quality. The secondary outcomes were adverse events, satisfaction rates, HSS scores, and SF-12 scores. The longest follow-up was 2 years. Results: The two groups showed no differences in terms of characteristics (P > 0.05). Group B had lower resting VAS pain scores (1.54 ± 0.60, 95% CI = 1.37 to 1.70 vs. 2.00 ± 0.63, 95% CI = 2.05 to 2.34) and active VAS pain scores (2.64 ± 0.62, 95% CI = 2.46 to 2.81 vs. 3.16 ± 0.75, 95% CI = 2.95 to 3.36) within 48 h postoperatively than Group A (P < 0.001), while none of the pain differences exceeded the minimal clinically important difference (MCID). Group B had significantly lower CRP levels (59.49 ± 13.01, 95% CI = 55.88 to 63.09 vs. 65.95 ± 14.41, 95% CI = 61.95 to 69.94) and IL-6 levels (44.11 ± 13.67, 95% CI = 40.32 to 47.89 vs. 60.72 ± 15.49, 95% CI = 56.42 to 65.01), lower opioid consumption (7.60 ± 11.10, 95% CI = 4.52 to 10.67 vs. 13.80 ± 14.68, 95% CI = 9.73 to 17.86), better ROM (110.20 ± 10.46, 95% CI = 107.30 to 113.09 vs. 105.30 ± 10.02, 95% CI = 102.52 to 108.07), better sleep quality (3.40 ± 1.03, 95% CI = 3.11 to 3.68 vs. 4.20 ± 1.06, 95% CI = 3.90 to 4.49), and higher satisfaction rates than Group A within 48 h postoperatively (P < 0.05). Adverse events, HSS scores, and SF-12 scores were not significantly different within 2 years postoperatively. Conclusions: A cocktail of ropivacaine, morphine, and Diprospan prolongs the analgesic effect up to 48 h postoperatively. Although the small statistical benefit may not result in MCID, the LIA cocktail still reduces opioid consumption, results in better sleeping quality and faster rehabilitation, and does not increase adverse events. Therefore, cocktails of ropivacaine, morphine, and Diprospan have good application value for pain control in TKA. This trial is registered with ChiCTR1800018372.

Betamethasone Dipropionate Derivatization, Biotransformation, Molecular Docking, and ADME Analysis as Glucocorticoid Receptor.

Betamethasone is an important glucocorticoids (GCs), frequently used to cure allergies (such as asthma and angioedema), Crohn's disease, skin diseases (such as dermatitis and psoriasis), systemic lupus erythematosus, rheumatic disorders, and leukemia. Present investigation deals to find potential agonist of glucocorticoid receptors after biotransformation of betamethasone dipropionate (1) and to carry out the molecular docking and ADME analyses. Biotransformation of 1 was carried out with Launaea capitata (dandy) roots and Musa acuminate (banana) leaves. M. acuminate furnished low-cost value-added products such as Sananone dipropionate (2) in 5% yields. Further, biocatalysis of Sananone dipropionate (2) with M. acuminate gave Sananone propionate (3) and Sananone (4) in 12% and 7% yields, respectively. However, Sananone (4) was obtained in 37% yields from Launaea capitata. Compound 5 was obtained in 11% yield after ß-elimination of propionic acid at C-17 during oxidation of compound 1. The structure elucidation of new compounds 2-5 was accomplished through combined use of X-ray diffraction and NMR (1D and 2D) studies. In addition to this, molecular docking and ADME analyses of all transformed products of 1 were also done. Compounds 1-5 showed -12.53 to -10.11 kcal/mol potential binding affinity with glucocorticoid receptor (GR) and good ADME profile. Moreover, all the compounds showed good oral bioavailability with the octanol/water partition coefficient in the range of 2.23 to 3.65, which indicated that compounds 1-5 were in significant agreement with the given criteria to be considered as drug-like.

Betamethasone Dipropionate Nanocrystals: Investigation, Feasibility and In Vitro Evaluation.

Corticosteroids, such as betamethasone dipropionate (BMD), have been the mainstay in topical therapy as potent glucocorticoid receptor agonist with immune suppression, anti-proliferative, and anti-inflammatory effects. Moreover, they have poor skin penetration, which is a hurdle against its potential therapeutic benefits. In present investigation, nanocrystals as carrier for effective topical delivery of BMD were explored using wet milling as technique and polysorbate 80 as a non-ionic stabilizer. Upon optimizing different process parameters, promising results were observed at stabilizer concentration of 0.9% w/v having particle size analysis (PSA) and PDI as 284 nm and 0.299, respectively. These results were supported by the FTIR and PXRD spectra of BMD-API and BMD nanocrystals, suggesting strong crystal lattice structure of BMD being reduced due to milling. The reduction in particle morphology was evident from the FESEM images. The optimized batch of BMD nanocrystals was incorporated into Carbopol gel base, showing pH 6.2 ± 0.2 and viscosity 87.00 ± 5.2 Pa s at 25°C. A drug diffusion study using Franz diffusion cell proclaimed around ~86% BMD release from nanogel across the membrane. Also, it was observed that the BMD permeation across the skin was 2.39-fold higher with marketed formulation in contrast to BMD nanogel, suggesting prolonged drug release. The skin permeation flux with nanogel was at a much lower rate along with ~50.27% drug retention in different strata of skin, resulting in retention of drug nanocrystals. Thus, in nutshell the prolonged drug release from nanogel would fulfill the aim of once a day application and would aid in reducing the adverse events associated with repeated drug applications.

A new cocktail formula with diprospan of local infiltration analgesia in primary total hip arthroplasty: A prospective, randomized, controlled, observer-blinded study.

OBJECTIVE: This study aimed to observe the analgesic effect of the cocktail formulation with diprospan during total hip arthroplasty (THA). METHODS: From September 2018 to April 2019, 120 patients undergoing primary unilateral THA were included in this prospective, randomized, observer-blinded study. Patients were randomized into three groups, according to the different local infiltration analgesia (LIA) strategies: LIA with ropivacaine (the ropivacaine group, n = 40), LIA with a new cocktail containing ropivacaine, diprospan, and morphine (the cocktail group, n = 40), and the control group (n = 40). The primary outcomes included postoperative pain scores. The resting visual analogue scale (VAS) scores were measured at 2, 6, and 12 h after the surgery (a.m. and p.m.) on postoperative day (POD) 1, POD2, and the day of discharge. Movement VAS scores were assessed at 6 h, 12 h after the operation (a.m. and p.m.) on POD1, POD2, and the day of discharge. The secondary outcomes included opioid consumption, postoperative hospital stay, range of motion of the hip at discharge, patient satisfaction, and the results of the follow-up. RESULTS: After the screening, 120 patients were randomized into three groups (40 patients in each group). All of the patients completed the trial. The resting VAS scores in the ropivacaine group and cocktail group at 2 h were lower than those in the control group (P < 0.001 and P < 0.001, respectively, F = 17.054), and the same trend was also postoperatively found at 6 h (p = 0.005 and P = 0.002, F = 6.212). Twelve hours after the operation, the pain score in the cocktail group was lower than that in the other two groups, but only the difference between the cocktail group and the control group was statistically significant (P = 0.018, F = 3.144). From the morning of the first postoperative day to the a.m. on POD 2, the VAS scores in the cocktail group were significantly lower than those in the ropivacaine group and the control group. Furthermore, the movement VAS scores in the ropivacaine group and the cocktail group were better than those in the control group at 6 and 12 h post-operation (P < 0.05). The per capita opioid consumption in the cocktail group was less than that in the ropivacaine group and the control group within 24 h post-operation. There were no significant differences in the comparison of additional indicators among the three groups. CONCLUSION: The new cocktail with diprospan had a better result and longer duration time for early postoperative pain control in primary THA via the posterolateral approach under general anesthesia, especially for treating resting pain.

The Effect of the Long-Term Calcipotriol/Betamethasone Dipropionate Local Therapy on Tissue Resident Memory Cells Markers in Psoriatic Eruptions.

BACKGROUND: The natural course of psoriasis is characterized by the long-term persistence of lesions and a predilection for relapse in the same area. It is caused by the inherence of TRM (tissue resident memory T cells) in apparently healthy skin. These cells are able to initiate an inflammatory cascade and induce relapse of the disease. These cells are characterized by high resistance to damaging factors and apoptosis, which determines their longevity. AIM: The aim of our study was to evaluate the presence of TRM in psoriatic plaques before, during and after 12 weeks of therapy in patients treated with topical calcipotriol and betamethasone dipropionate (Cal/BD) foam. METHODS: TRM markers (CD4, CD8, CD103, CD69, CD49, CXCR6) and tissue expression of cytokines (IL-17A, IL-22) in the lesional psoriatic skin from 10 patients compared to 10 healthy skin samples were estimated by immunohistochemistry. Biopsy samples from the area of the same psoriatic plaque were collected three times: before the initiation of therapy, 4 and 12 weeks after its initiation. RESULTS: The presence of TRM markers in the epidermis and dermis of psoriatic lesions was significantly higher when compared to the skin of control group patients. A reduction in the expression of the characteristic TRM markers (CD8, CD4, CD103, CD69, CXCR6, IL-17A and IL-22) was observed in the epidermis on week 12 of therapy, while a depletion in the expression of TRM in the dermis was demonstrated only in CD4 and IL-22. CONCLUSIONS: Topical treatment with Cal/BD foam significantly decreased the expression of TRM markers mainly in the epidermis, and to a lesser extent in the dermis, during the 12-week observation period. It probably results from a worse penetration of the drug into the dermis and the effect of the preparation mainly on the epidermis. The persistence of a high expression of TRM markers in the dermis may result in the rapid recurrence of lesions after discontinuation of topical treatment.

The effect of dilution of fusidic acid cream and betamethasone dipropionate cream in complex extemporaneous mixes on formulation performance.

The Aron regimen is an unconventional therapy which entails frequent applications of an extemporaneously prepared three component system (a topical antibiotic, a corticosteroid and an emollient), with the intention of decolonising the skin of S. aureus whilst treating atopic dermatitis. The impact of heavily diluting these topical medicinal products, to differing extents, on formulation performance is not well understood thus was investigated in this study. Following a single application of a range of compounded Aron mixes (fusidic acid and betamethasone dipropionate diluted to varying extents in an emollient base), significant reductions in the expected drug flux across silicone membrane, ex vivo percutaneous absorption and skin retention of both drugs relative to the marketed products were observed. This was attributed to a number of complex formulation effects making such changes difficult to predict in a clinical setting. Further investigations are required to evaluate the impact of frequent applications of the Aron mix to widespread areas on clinical efficacy, antimicrobial resistance and long term side effects.

Coupling AFM, DSC and FT-IR towards Elucidation of Film-Forming Systems Transformation to Dermal Films: A Betamethasone Dipropionate Case Study.

Polymeric film-forming systems have emerged as an esthetically acceptable option for targeted, less frequent and controlled dermal drug delivery. However, their dynamic nature (rapid evaporation of solvents leading to the formation of thin films) presents a true characterization challenge. In this study, we tested a tiered characterization approach, leading to more efficient definition of the quality target product profiles of film-forming systems. After assessing a number of physico-chemico-mechanical properties, thermal, spectroscopic and microscopic techniques were introduced. Final confirmation of betamethasone dipropionate-loaded FFS biopharmaceutical properties was sought via an in vitro skin permeation study. A number of applied characterization methods showed complementarity. The sample based on a combination of hydrophobic Eudragit® RS PO and hydroxypropyl cellulose showed higher viscosity (47.17 ± 3.06 mPa·s) and film thickness, resulting in sustained skin permeation (permeation rate of 0.348 ± 0.157 ng/cm2 h), and even the pH of the sample with Eudragit® NE 30D, along with higher surface roughness and thermal analysis, implied its immediate delivery through the epidermal membrane. Therefore, this study revealed the utility of several methods able to refine the number of needed tests within the final product profile.

Efficacy, quality of life, and treatment satisfaction: an indirect comparison of calcipotriol/betamethasone dipropionate cream versus foam for treatment of psoriasis.

OBJECTIVE: To assess how the use of calcipotriol and betamethasone dipropionate (Cal/BDP) cream impacted efficacy, patients' quality of life (QoL), and treatment satisfaction versus Cal/BDP foam. METHODS: Data from clinical trials of Cal/BDP cream and foam were analyzed, by applying the common anchor Cal/BDP gel. Efficacy was assessed by Physician Global Assessment (PGA) treatment success and ≥75% reduction in Psoriasis Area and Severity Index (PASI75 response); QoL by Dermatology Life Quality Index (DLQI); treatment satisfaction by Psoriasis Treatment Convenience Scale (PTCS) and Topical Product Usability Questionnaire (TPUQ). RESULTS: Treatment with Cal/BDP cream was on par with foam on PGA treatment success (risk ratio (RR) for Cal/BDP cream versus foam: 0.80; 95%CI: 0.56, 1.14; p = .21) and PASI75 response (RR for Cal/BDP cream vs. foam: 0.85; 95%CI: 0.64, 1.13; p = .27) when assessed at the treatment duration of 8 weeks for Cal/BDP cream and 4 weeks for Cal/BDP foam. Treatment with Cal/BDP cream was associated with significantly greater treatment satisfaction versus foam on the domains: overall treatment satisfaction (p = .01), "ease of application" (p < .001), "lack of greasiness" (p < .001), "moisturizing effect" (p = .01), and almost significantly greater improvement on the domain "easily incorporated into daily routine" (p = .07). Furthermore, there was a trend for greater DLQI improvement with cream versus foam when assessed at recommended treatment duration [mean difference (MD) for Cal/BDP cream vs. foam: -1.00; 95%CI: -2.20, 0.20; p = .10]. CONCLUSIONS: Indirect comparison analyses showed that Cal/BDP cream significantly improves treatment satisfaction and tends to improve QoL versus foam. Cal/BDP cream is on par with foam on efficacy.

The Maintenance Effect of Calcipotriene 0.05% and Betamethasone Dipropionate 0.064% (Cal/BD) Aerosol Foam in Combination With Apremilast.

Even in light of significant recent therapeutic advancements, many patients with psoriasis will use a combination of treatments at some point in the disease course. Despite the frequency with which combinations are used in clinical practice, there are few large-scale, randomized controlled trials investigating the use of various combination therapies in psoriasis. Twice-weekly maintenance application of topical Cal/BD aerosolized foam has recently been shown to prolong time to remission and is associated with fewer relapses in patients initially treated with standard dosing of the formulation. Data from a small number of pilot studies suggest potential benefits from the combined used topical Cal/BD foam with oral apremilast. This pilot study assesses the effect of twice-weekly maintenance doses of Cal/BD foam after 4 weeks of standard once-daily treatment in combination with apremilast. The combination of apremilast plus Cal/BD achieved the primary endpoint, with 95% of subjects rated clear or almost clear on PGA at week 4. Subject’s global assessment scores showed similar improvement to PGA scores at week 4 (47% of subjects clear or almost clear). Ten subjects (53%) achieved PASI 75 at week 4, and 12 (63%) achieved PASI 75 at week 16. Maintenance dosing of Cal/BD foam in combination with apremilast is safe and effective for the management of moderate psoriasis. J Drugs Dermatol. 2022;21(4):381-386. doi:10.36849/JDD.6622.

Adjunctive Use of Calcipotriene 0.005%/Betamethasone Dipropionate 0.064% Foam in Patients With Psoriasis Treated With Ixekizumab.

OBJECTIVE: To examine the effectiveness and safety of adjunctive treatment with calcipotriene 0.005%/betamethasone dipropionate 0.064% (Cal/BD) foam in adult patients with chronic plaque psoriasis who have localized residual plaques after ≥24 weeks of treatment with ixekizumab biologic therapy. METHODS: This study was a prospective, open-label, single-arm study of adult patients with moderate-to-severe chronic plaque psoriasis who had suboptimal response after ≥24 weeks of treatment with ixekizumab (residual 3–8% body surface area [BSA] involvement). All patients continued treatment with ixekizumab and received once-daily Cal/BD foam for 4 weeks, followed by every other day for weeks 8 to 12. The primary endpoint was treat-to-target BSA ≤1% at week 4. Additional endpoints included the Physician’s Global Assessment (PGA) score, PGA×BSA, and the patient-reported Dermatology Life Quality Index (DLQI). Safety evaluations included assessments of adverse events (AEs) and local skin reactions. RESULTS: Among 25 enrolled patients, 36% were female, and the mean age was 50 years. After 4 weeks of daily Cal/BD foam, 56% of patients achieved the treat-to-target goal of ≤1% BSA. Mean % BSA involvement, mean PGA score, and composite PGA×BSA score decreased 4 weeks after the addition of Cal/BD foam. Improvements in disease severity outcomes were maintained after reducing Cal/BD dosing frequency. Cal/BD was generally safe and well-tolerated, with no serious AEs reported. CONCLUSION: In real-world clinical practice, for patients with moderate-to-severe plaque psoriasis who had residual plaques following ≥24 weeks of ixekizumab monotherapy, adjunctive treatment with Cal/BD foam was associated with notable and sustained improvements in disease control. J Drugs Dermatol. 2022;21(3): 235-240. doi:10.36849/JDD.6396.

Pooled Analysis Demonstrating Superior Patient- Reported Psoriasis Treatment Outcomes for Calcipotriene/ Betamethasone Dipropionate Cream Versus Suspension/Gel.

BACKGROUND: Calcipotriene and betamethasone dipropionate (CAL/BDP) cream is a novel treatment of plaque psoriasis based on PAD™ Technology (PAD-cream) designed to improve patient reported treatment satisfaction and quality of life (QoL). METHOD: A pooled analysis of patient reported outcomes from two phase 3, multicenter, randomized, investigator-blind, active, and vehicle-controlled trials evaluating a total of 1271 patients with mild to moderate plaque psoriasis according to the Physician Global Assessment (PGA) scale. Products were applied once daily for 8 weeks. RESULTS: The proportion of patients evaluating their treatment to have improved by 2 grades to clear or very mild disease on the 5-grade Subject Global Assessment (SGA) scale, defined as SGA Success, was significantly higher in the CAL/BDP PAD-cream group compared to active comparator (CAL/BDP suspension/gel) (week 8, 44.2% vs 27.9%, P<0.0001). A Dermatology Life Quality Index (DLQI) score of 0 or 1, indicating no impact of disease on the patient's life, was obtained by 43.8% of patients at week 8 in the CAL/BDP cream group versus 34.2% in the CAL/BDP suspension/gel group (P=0.0005). CAL/BDP PAD-cream demonstrated significantly greater psoriasis treatment convenience compared to CAL/BDP suspension/gel at all studied time points, including questions addressing greasiness of the formulation and overall satisfaction of treatment. CONCLUSION: CAL/BDP PAD-cream is a novel topical treatment for psoriasis, which through PAD™ Technology offers substantial improvement in QoL and treatment satisfaction for patients. Given these data, CAL/BDP PAD-cream may lead to better adherence to treatment, which ultimately could result in better treatment outcomes in clinical practice. CLINICALTRIALS: gov: NCT03308799 and NCT03802344. J Drugs Dermatol. 2022;21(3):242-248. doi:10.36849/JDD.6611.

Long-term maintenance treatment of psoriasis: the role of calcipotriol/betamethasone dipropionate aerosol foam in clinical practice.

Most patients with psoriasis present with localized mild-to-moderate disease. In this case, the application of topical treatments in the first-line setting is recommended in most cases.Among different topical options, the fixed-dose combination of betamethasone dipropionate (BD) and vitamin D analogue (Cal) aerosol foam (Enstilar®, Leo Pharma) is approved as first-line topical therapy for the treatment of psoriasis in USA and the EU, due to its high efficacy and its favorable administration scheme.The PSO-LONG was the first trial to report on the long-term efficacy and safety of the Cal/DB foam treatment for the proactive management of psoriasis and now, the indications of Cal/BD foam included its use in the psoriasis maintenance treatment. However, the precise role of this treatment and the potential therapeutic schemes in the long-term management of psoriasis need further clarification.This Position Paper, authored by a group of Italian Expert Dermatologists, critically discusses the long-term management of psoriasis with Cal/BD foam in clinical practice. In particular, the biological rationale in the proactive treatment with Cal/BD foam and current evidence regarding this therapeutic approach are presented, along with its application also in patients with moderate-to-severe disease, difficult-to-treat lesions, or within combination regimens. In addition, strategies to improve adherence to long-term treatment of psoriasis are discussed.

Betamethasone phosphate reduces the efficacy of antenatal steroid therapy and is associated with lower birthweights when administered to pregnant sheep in combination with betamethasone acetate.

BACKGROUND: Antenatal corticosteroid therapy is a standard of care for women at imminent risk of preterm labor. However, the optimal (maximum benefit and minimal risk of side effects) antenatal corticosteroid dosing strategy remains unclear. Although conveying overall benefit when given to the right patient at the right time, antenatal corticosteroid treatment efficacy is highly variable and is not risk-free. Building on earlier findings, we hypothesized that when administered in combination with slow-release betamethasone acetate, betamethasone phosphate and the high maternal-fetal betamethasone concentrations it generates are redundant for fetal lung maturation. OBJECTIVE: Using an established sheep model of prematurity and postnatal ventilation of the preterm lamb, we aimed to compare the pharmacodynamic effects of low-dosage treatment with betamethasone acetate only against a standard dosage of betamethasone phosphate and betamethasone acetate as recommended by the American College of Obstetricians and Gynecologists for women at risk of imminent preterm delivery between 24 0/7 and 35 6/7 weeks' gestation. STUDY DESIGN: Ewes carrying a single fetus at 122±1 days' gestation (term=150 days) were randomized to receive either (1) maternal intramuscular injections of sterile saline (the saline negative control group, n=12), (2) 2 maternal intramuscular injections of 0.25 mg/kg betamethasone phosphate+betamethasone acetate administered at 24-hour dosing intervals (the betamethasone phosphate+betamethasone acetate group, n=12); or (3) 2 maternal intramuscular injections of 0.125 mg/kg betamethasone acetate administered at 24-hour dosing intervals (the betamethasone acetate group, n=11). The fetuses were surgically delivered 48 hours after treatment initiation and ventilated for 30 minutes to determine functional lung maturation. The fetuses were euthanized after ventilation, and the lungs were collected for analysis using quantitative polymerase chain reaction and Western blot assays. Fetal plasma adrenocorticotropic hormone levels were measured in the cord blood samples taken at delivery. RESULTS: Preterm lambs were defined as either antenatal corticosteroid treatment responders or nonresponders using an arbitrary cutoff, being a PaCO2 level at 30 minutes of ventilation being more extreme than 2 standard deviations from the mean value of the normally distributed saline control group values. Compared with the animals in the saline control group, the animals in the antenatal corticosteroid treatment groups showed significantly improved lung physiological responses (blood gas and ventilation data) and had a biochemical signature (messenger RNA and surfactant protein assays) consistent with functional maturation. However, the betamethasone acetate group had a significantly higher treatment response rate than the betamethasone phosphate+betamethasone acetate group. These physiological results were strongly correlated to the amount of surfactant protein A. Birthweight was lower in the betamethasone phosphate+betamethasone acetate group and the fetal hypothalamic-pituitary-adrenal axis was suppressed to a greater extent in the betamethasone phosphate+betamethasone acetate group. CONCLUSION: Low-dosage antenatal corticosteroid therapy solely employing betamethasone acetate was sufficient for fetal lung maturation. The elevated maternal-fetal betamethasone concentrations associated with the coadministration of betamethasone phosphate did not in addition improve lung maturation but were associated with greater fetal hypothalamic-pituitary-adrenal axis suppression, a lower antenatal corticosteroid treatment response rate, and lower birthweight-outcomes not desirable in a clinical setting. These data warranted a clinical investigation of sustained low-dosage antenatal corticosteroid treatments that avoid high maternal-fetal betamethasone exposures.

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.

A pooled analysis of randomized, controlled, phase 3 trials investigating the efficacy and safety of a novel, fixed dose calcipotriene and betamethasone dipropionate cream for the topical treatment of plaque psoriasis.

BACKGROUND: Plaque psoriasis is a common, chronic and relapsing inflammatory skin disease clinically characterized by erythema and scaling desquamation. As over 90% of psoriasis patients benefit from topical therapies, local treatments continue to play an eminent role in management strategies. One such topical treatment is the fixed dose combination of calcipotriol (CAL) and betamethasone dipropionate (BDP). OBJECTIVES: Pooled analysis of two different phase 3 clinical trails to compare superiority regarding efficacy, safety and quality of life (QoL) between CAL/BDP PAD-cream and CAL/BDP TS. METHODS: The data from two phase 3, multicentre, randomized, investigator-blind, active and vehicle-controlled trials enrolling patients with psoriasis were pooled and analysed. Investigational products included a CAL/BDP cream based on PAD™ Technology (PAD-cream) designed for high skin penetration and increased patient preference, an active control (marketed CAL/BDP topical suspension/gel, in the following abbreviated as CAL/BDP TS) and cream vehicle, which were applied once daily for 8 weeks. RESULTS: Efficacy and safety of the novel CAL/BDP PAD-cream formulation for the topical treatment of psoriasis demonstrated superiority for all efficacy end points after 8 weeks of treatment. PGA treatment success for CAL/BDP PAD-cream (43.2%) was greater than CAL/BDP TS (31.9%; P < 0.0001), the mean per cent reduction in mPASI for CAL/BDP PAD-cream was 64.6% compared to 56.4% for CAL/BDP TS (P < 0.0001) and DLQI 0/1 was obtained by 43.8% in the CAL/BDP PAD-cream group versus 34.2% in the CAL/BDP TS group (P = 0.0005). There was no adverse drug reaction reported with a frequency of >1%, associated with the CAL/BDP PAD-cream. CONCLUSIONS: The novel fixed dose combination CAL/BDP PAD-cream offers greater efficacy, superior patient QoL and equivalent favourable safety for the topical treatment of psoriasis, in comparison to the currently available topical suspension/gel.

Effect of halometasone cream combined with Simiao pill on the therapeutic effect and expression of serum leukotriene B4 (LTB4) and thymic stromal lymphopoietin (TSLP) in patients with eczema, and the factors influencing its clinical efficacy.

BACKGROUND: Chronic eczema has the characteristics of a long treatment cycle and repeated attacks, which seriously affects the daily life and work of patients. Topical glucocorticoids are the first-line treatment for chronic eczema. This study aimed to retrospectively analyze the effects of halometasone cream combined with Simiao pill on the efficacy and expression of serum leukotriene B4 (LTB4) and thymic stromal lymphopoietin (TSLP) in patients with eczema, and identify the factors influencing its clinical efficacy. METHODS: We retrospectively collected the medical records of 195 patients with chronic eczema treated in the dermatology department from January 2020 to May 2021, and divided them into two groups according to medication: 98 cases were treated with halometasone cream (control group) and 97 cases were treated with halometasone ointment combined with Simiao pill (observation group). The severity of eczema, quality of life, clinical efficacy, LTB4 and TSLP levels, and safety were compared between the two groups. Multivariate logistic regression analysis was used to determine the independent factors affecting clinical efficacy. RESULTS: After treatment, the Eczema area and severity index (EASI) and Dermatology Life Quality Index (DLQI) scores in the observation group were markedly lower than those of the control group (P<0.05). The total clinical effective rate of the observation group was 88.8%, which was notably higher than that of the control group 70.1% (P=0.001). The concentrations of serum LTB4 and TSLP in the observation group were markedly lower than those in the control group (P<0.05). Logistic regression analysis showed that the treatment regimen, digestive system symptoms, heavy aching limbs, and damp-heat tongue and pulse were independent factors affecting the curative effect of the patients (P<0.05). CONCLUSIONS: Simiao pill combined with halometasone cream can effectively improve chronic eczema and enhance the clinical efficacy of treatment, which may be related to the reduction of serum LTB4 and TSLP levels. The treatment plan, digestive system symptoms, heavy aching limbs, and damp-heat tongue and pulse are the main factors that affecting the clinical curative effect. Thus, clinical intervention programs should be made according to the above factors to improve the quality of life of patients.

The continued inappropriate use and overuse of combination topical clotrimazole-betamethasone.

OBJECTIVE: Combination topical clotrimazole/ betamethasone dipropionate (C-BM) contains a high-potency topical corticosteroid and is not infrequently prescribed for inappropriate patient groups and body sites. Use of C-BM can lead to inadequate clearance or exacerbation of fungal infections as well as cutaneous atrophy, striae, and other skin maladies. METHODS: We performed a retrospective chart review of 1,978 clinical visits where C-BM was prescribed within the University of Utah Health system between 2014 and 2018 to better understand current prescribing patterns. RESULTS: 1,974 prescriptions were written for C-BM. 91.6% of patients were at least the recommended age of 17 years. C-BM was most commonly prescribed for rashes of an inflammatory (42.2%) or fungal nature (38.1%). Clotrimazole/betamethasone dipropionate was prescribed for sensitive areas (face, axillae, groin or diaper region) in 48.9% of patients. Family medicine clinicians prescribed 58.3% of C-BM prescriptions, whereas dermatology clinicians accounted for 3.4%. CONCLUSION: We strongly recommend clinicians use alternative treatments for rashes or refer to dermatologists.

Development and validation of a RP-UPLC method for the determination of betamethasone dipropionate impurities in topical formulations using a multivariate central composite design.

The current study presents a specific, accurate, simple, and rapid UPLC method for the determination of impurities present in cream and ointment formulations of betamethasone dipropionate (BMD). The analytical method was optimized using central composite design (CCD) prior to the method validation. Critical Process Parameters (CPPs) and Critical Quality Attributes (CQAs) were identified for the analytical method. A total of 17 experiments were carried out and verified the individual and interaction effects of CPPs. The CPPs were optimized using a numerical method by keeping the CQAs within the desired range (R1-R2: minimize & R3-R5: maximize) as an optimization goal. Optimized chromatographic separation was achieved using a Waters Acquity UPLC BEH C18, 100 mm × 2.1 mm, 1.7 µm column with a gradient mode of elution comprising 20 mM phosphate buffer: ACN 70 : 30, v/v as mobile phase-A and 20 mM phosphate buffer: ACN 30 : 70, v/v as mobile phase-B. The developed method was validated in accordance with ICH guidelines. The validation data conclude that the developed method is specific, accurate, linear, precise, rugged, and robust for the quantification of impurities in BMD topical formulations.