Drugs in Context最新文献

Psoriatic arthritis is a chronic systemic inflammatory disease that presents with a variable clinical course and is typically associated with joint inflammation, together with cutaneous psoriasis. In recent decades, knowledge of the pathogenesis of psoriatic arthritis has advanced considerably and has allowed for development of new highly effective therapies, transforming the treatment landscape. Upadacitinib is a Janus kinase inhibitor (JAK) that is orally reversible with high selectivity for JAK1 and its signal transduction molecules. The results obtained in the phase III clinical trials (SELECT-PsA 1 and SELEC-PsA 2) demonstrated that upadacitinib was highly effective over placebo and non-inferior to adalimumab in several important domains of the disease. Improvements were observed in dactylitis, enthesitis and spondylitis as well as in physical function, pain, fatigue and overall quality of life. The safety profile of these results resembled that of adalimumab, apart from a slightly higher rate of herpes zoster infection, an increase of creatine kinase and an incidence of lymphopenia. However, none of these events was considered a serious adverse advent. Additionally, another analysis demonstrated that combining upadacitinib with methotrexate was associated with a similar efficacy to upadacitinib in monotherapy, both for patients that are naive to biologics treatment and for those previously treated with biologics. Therefore, upadacitinib is a new option for the treatment of psoriatic arthritis, presenting a series of beneficial characteristics. At this stage, it is important to collect long-term data to confirm the efficacy and safety profiles shown in clinical trials.

Psoriatic arthritis (PsA) is a heterogeneous disease that may develop in up to 30% of patients with psoriasis. PsA mainly involves peripheral joints; however, axial skeleton and entheses can also be involved. PsA is the result of a complex interplay between an individual's genotype and environmental factors that triggers an immune response and leads to the production of a cytokine cascade. Even though there are about 17 targeted therapies for PsA, a significant percentage of patients fail to respond to such treatments, have a partial response or develop side-effects. This article aims to review the current knowledge on deucravacitinib, a new oral small molecule that selectively inhibits tyrosine kinase 2 (TYK2), for the treatment of PsA. TYK2, a member of the Janus kinase (JAK) family, is responsible for mediating intracellular signalling of cytokines involved in the pathogenesis of PsA and psoriasis, namely IL-12, IL-23, and type I interferons. Recently, deucravacitinib was approved by the FDA for the treatment of moderate-to-severe plaque psoriasis and is currently being evaluated in phase III clinical trials in PsA. In a phase II clinical trial, deucravacitinib showed sustained effectiveness in several domains of PsA, namely arthritis, enthesitis and dactylitis, was well tolerated, and had a favourable safety profile. In patients with psoriasis, deucravacitinib had shown a higher efficacy than placebo and apremilast. Deucravacitinib is a promising therapy, with a unique mechanism of action. Results from the phase III programme and studies evaluating long-term response and head-to-head comparisons with other targeted agents will be important to establishing the position of deucravacitinib in the management of PsA.

Non-alcoholic fatty liver disease is one of the main causes of elevated liver enzymes and chronic liver disease worldwide. It ranges from steatosis to steatohepatitis, leading to cirrhosis and related liver dysfunction. Silymarin is a herbal medicine, mostly used for liver disorders owing to its supposed hepatoprotective action. This report recommends silymarin in a patient with diabetes and grade II non-alcoholic steatohepatitis, confirming significant hepatoprotective effects as shown by the reduction of liver enzyme activities. This article is part of the Current clinical use of silymarin in the treatment of toxic liver diseases: a case series Special Issue: https://www.drugsincontext.com/special_issues/current-clinical-use-of-silymarin-in-the-treatment-of-toxic-liver-diseases-a-case-series.

Metabolic-associated fatty liver disease (MAFLD) is the main condition of altered liver enzymes worldwide. With a constant increase in liver hospitalizations, MAFLD is the second cause of cirrhosis and soon will be the first cause of liver transplantation. Early recognition of MAFLD and a personalized approach are essential to its treatment. This case study presents personalized management of a patient with MAFLD with advanced fibrosis and severe steatosis. The impact of silymarin use, concomitant treatment with diet, exercise, insulin sensitizers and antifibrotic agents, was evaluated. This article is part of the Current clinical use of silymarin in the treatment of toxic liver diseases: a case series Special Issue: https://www.drugsincontext.com/special_issues/current-clinical-use-of-silymarin-in-the-treatment-of-toxic-liver-diseases-a-case-series.

Background: Challenging periods and/or mild micronutrient deficiencies may result in a lack of energy and general fatigue, frequently occurring in the general population. Supradyn Recharge and Supradyn Magnesium and Potassium (Mg/K) are multimineral/vitamin supplements formulated to ensure adequate daily intake of micronutrients. We conducted an observational study addressing consumption behaviour, reasons for intake, frequency of intake, and consumer experiences, satisfaction and characteristics under real-life conditions.

Methods: This was a retrospective, observational study carried out with two computer-aided web quantitative interviews.

Results: A total of 606 respondents (almost equally split between men and women; median age 40 years) completed the questionnaires. The majority indicated having a family, a job and a good level of education; they stated to be long-time and daily users, reporting an average daily intake of 6 days a week. More than 90% of consumers claimed they were satisfied, would use the products again and recommend them; over two-thirds felt the value for money was good. Supradyn Recharge has been mainly used to support lifestyle change and mental resilience, seasonal changes, and post-illness recovery. Supradyn Mg/K has been used to sustain or regain energy levels during hot weather or physical activity and as a support against stress. Users claimed a positive impact on quality of life.

Conclusion: Overall, the perception of benefit by consumers was extremely positive as reflected in their consumption behaviour, the majority of whom stated to be long-time users and daily consumers, with an average daily intake of 6 days for both products. These data complement and add up to the results of Supradyn clinical trials.

Background: Advanced breast cancer (ABC) is characterized by multidimensional clinical complexity that is usually not considered in randomized clinical trials. In the present real-life study, we investigated the link between clinical complexity and quality of life of patients with HR⁺/HER2^- ABC treated with CDK4/6 inhibitors.

Methods: We evaluated multimorbidity burden assessed with the Cumulative Illness Rating Scale (CIRS), polypharmacy and patient-reported outcomes (PROs). PROs were assessed at baseline (T0), after 3 months of therapy (T1), and at disease progression (T2) using EORTC QLC-C30 and QLQ-BR23 questionnaires. Baseline PROs and changes between T0 and T1 were evaluated amongst patients with different multimorbidity burden (CIRS <5 and ≥5) and polypharmacy (<2 or ≥2 drugs).

Results: From January 2018 to January 2022, we enrolled 54 patients (median age 66 years, IQR 59-74). The median CIRS score was 5 (IQR 2-7), whilst the median number of drugs taken by patients was 2 (IQR 0-4). No changes in QLQ-C30 final scoring between T0 and T1 were observed in the overall cohort (p=0.8944). At T2, QLQ-C30 global score deteriorated with respect to baseline (p=0.0089). At baseline, patients with CIRS ≥5 had worse constipation than patients without comorbidities (p<0.05) and a lower trend in the median QLQ-C30 global score. Patients on ≥2 drugs had lower QLQ-C30 final scores and worse insomnia and constipation (p<0.05). No change in QLQ-C30 final score from T0 to T1 was observed (p>0.05).

Conclusion: Multimorbidity and polypharmacy increase the clinical complexity of patients with ABC and may affect baseline PROs. The safety profile of CDK4/6 inhibitors seems to be maintained in this population. Further studies are needed to assess clinical complexity in patients with ABC.This article is part of the Tackling clinical complexity in breast cancer Special Issue: https://www.drugsincontext.com/special_issues/tackling-clinical-complexity-in-breast-cancer/.

Background: In psoriasis, poor treatment adherence is frequently related to low efficacy and limited cosmetic acceptability from the patients' perspective. This study aimed to characterize the sensorial attributes of a calcipotriol (CAL) and betamethasone dipropionate (BDP)-cream vehicle based on polyaphron dispersion (PAD) Technology and to compare them with the conventional ointment and oleogel formulations for psoriasis.

Methods: A panel of 16 experts assessed sensory properties at four different stages: appearance, pick up, rub out and afterfeel. Descriptive sensory analysis was used to evaluate relevant attributes. Each attribute was rated on a line scale (range 0-100%). Active ingredients were not used because panellists were healthy volunteers, and vehicle formulations needed to be used instead.

Results: CAL/BDP PAD-cream vehicle was evaluated as having a low stickiness, low grease behaviour, good wetness, and good spreadability. Ointment showed the least desirable behaviour regarding these properties. Moreover, once CAL/BDP PAD-cream vehicle was absorbed, the gloss disappeared quickly, leaving low stickiness and a low amount of residue. This afterfeel behaviour was not observed with ointment. The oleogel formulation had good sensory properties, similar to CAL/BDP PAD-cream vehicle, but with lower integrity of shape, lower wetness and higher greasiness.

Conclusion: Overall, CAL/BDP PAD-cream vehicle has the desirable requirements for a topical product for the treatment of psoriasis, with better sensory properties than ointment and easier manipulation than oleogel, which may lead to greater acceptance and adherence.

Background: Due to changing face of dermatophytosis in India, many dermatologists practice different dosing patterns of itraconazole (ITZ). Recently, a new form of ITZ, super-bioavailable ITZ (SBITZ), has been commercialized to overcome the pharmacokinetic challenges of conventional ITZ (CITZ). Serum and sebum concentration of ITZ plays an important role in the management of dermatophytosis. Hence, the current study compares the rate and extent of serum and sebum concentration of SBITZ and CITZ at different dosing to determine their efficacy and safety in patients with dermatophytosis.

Methods: This was an open-label, randomized, four-arm study including 40 adult patients diagnosed with glabrous tinea who were randomized equally into four groups to receive either CITZ-100-BD or CITZ-200-OD (2×100 mg capsules) or SBITZ-130-OD or SBITZ-100-OD (2×SBITZ-50 mg capsules) for 4 weeks. Serum and sebum samples were analysed at different time intervals along with clinical efficacy and safety.

Results: For serum concentration, on day 28, the arithmetic mean and standard deviation (SD) for CITZ-100-BD, CITZ-200-OD, SB-130-OD and SB100-OD were 1262±233.5 ng/mL, 1704±261.6 ng/mL, 1770±268.9 ng/mL and 1520±231.7 ng/mL, respectively, which was statistically significant for OD dosing of ITZ/SBITZ over CITZ-100-BD. Similarly, for sebum concentration, the arithmetic mean and SD for CITZ-100-BD, CITZ-200-OD, SB-130-OD and SB-100-OD were 1042±163.45 ng/mg, 1423±192.46 ng/mg, 1534±227.55 ng/mg and 1107±182.35 ng/mg, respectively, which was statistically significant for SB-130-OD and CITZ-200-OD over CITZ-100-BD and SBITZ-100-OD dosing. No significant difference was noted between SBITZ-130 and CITZ-200 (p=0.25). Only two patients achieved complete cure in the SBITZ-130 group, whereas no patients achieved the same in other groups (p=0.47). All the dosages were very well tolerated with only 12 adverse events reported by ten patients in all groups.

Conclusion: All formulations achieved desired serum and sebum concentrations required for efficacy in dermatophytosis, but SB 130 mg OD and CITZ 200 mg OD were statistically significant than other ITZ doses in achieving sebum concentration. Additionally, SBITZ 130 mg OD was bioequivalent to CITZ 200 mg OD and achieved similar results to those of CITZ 200 mg OD but at 35% lower drug concentrations.

Point-of-care ultrasound (POCUS) plays a strategic role in the diagnostic and therapeutic evaluation of critically ill patients and, especially, in those who are haemodynamically unstable. In this context, POCUS allows a more precise identification of the cause, its differential diagnosis, the eventual coexistence with another entity and, finally, guiding of the therapeutic approach. It implies a portable use of ultrasound in acute settings covering different specified protocols, such as echocardiography, vascular, lung or abdominal ultrasound. This article reviews POCUS application in the emergency department or the intensive care unit, focused on severely compromised patients with cardiogenic shock with an emergent bedside assessment. Considering the high mortality rate of this entity, POCUS provides the intensivist/clinician with an appropriate tool for accurate diagnoses and a timely management plan. The authors propose practical algorithms for the diagnosis of patients using POCUS in these settings. This article is part of the Emerging concepts in heart failure management and treatment Special Issue: https://www.drugsincontext.com/special_issues/emerging-concepts-in-heart-failure-management-and-treatment.