Drugs in Context最新文献

The management of schizophrenia necessitates a comprehensive treatment paradigm that considers individual patient nuances and the efficacy of lurasidone in addressing schizophrenia symptoms, particularly at elevated dosages. Numerous randomized trials have affirmed the efficacy of lurasidone across various dimensions of schizophrenia, demonstrating marked enhancements in positive, negative and cognitive symptoms compared to a placebo. In addition, lurasidone exhibits potential in ameliorating agitation amongst acutely ill patients, showcasing greater efficacy at higher doses. However, despite the favourable outcomes observed with higher lurasidone doses, routine clinical practice often opts for lower doses, potentially limiting its maximal therapeutic impact. Furthermore, lurasidone also shows efficacy in reducing post-psychotic depression in dual psychosis. Moreover, practical insights into lurasidone usage encompass swift dose escalation within a 1-5-day span and recommended combination strategies with other medications such as benzodiazepines for insomnia or agitation, beta-blockers for akathisia, and antihistamines or antimuscarinic drugs for patients transitioning rapidly from antipsychotics with substantial antihistamine and/or anticholinergic effects. Finally, a series of clinical cases is presented, highlighting benefits of lurasidone in terms of cognitive function, functional recovery and other therapeutic aspects for the management of schizophrenia.

Psoriasis is a chronic inflammatory skin disease affecting 2-3% of the global population. Traditional systemic treatments, such as methotrexate, cyclosporine, acitretin and fumaric acid esters, have limited efficacy and are associated with significant adverse effects, necessitating regular monitoring and posing risks of long-term toxicity. Recent advancements have introduced biologic drugs that offer improved efficacy and safety profiles. However, their high cost and the inconvenience of parenteral administration limit their accessibility. Consequently, there is a growing interest in developing new, targeted oral therapies. Small molecules, such as phosphodiesterase 4 inhibitors (e.g. apremilast) and TYK2 inhibitor (e.g. deucravacitinib), have shown promising results with favourable safety profiles. Additionally, other novel oral agents targeting specific pathways, including IL-17, IL-23, TNF, S1PR1 and A3AR, are under investigation. These treatments aim to combine the efficacy of biologics with the convenience and accessibility of oral administration, addressing the limitations of current therapies. This narrative review synthesizes the emerging oral therapeutic agents for psoriasis, focusing on their mechanisms of action, stages of development and clinical trial results.

Bullous pemphigoid (BP) is an autoimmune bullous disease, typically affecting the elderly, characterized by the production of autoantibodies directed against structural components of the dermal-epidermal junction. An association between BP and psoriasis has been described several times, but the mechanisms underlying this association have yet to be clearly defined. The pathophysiological mechanism underlying psoriasis may be implicated in the pathogenesis of BP, as psoriasis precedes BP in most cases; in particular, a promoting role has been hypothesized by biologic therapies, which may induce a switch from a T helper 1 (T_H1)/T_H17-dominant cytokine milieu, typical of patients with psoriasis, to a T_H2-dominant one, typical of patients with BP. IL-17 inhibitors, in particular, have also been successfully used to treat BP in patients with psoriasis. The use of these drugs in these patients has been based on in vitro studies. However, cases of new-onset BP or relapses of BP already diagnosed in patients with psoriasis treated with biologic drugs have also been reported, and they occurred mainly in patients on anti-TNF drugs, yet very few cases with anti-IL-17A drugs have been described. We hereby describe two cases of new-onset BP in two patients treated with anti-IL-17 drugs for psoriasis.

Antibiotics are amongst the most prescribed medications globally in both inpatient and outpatient settings. Antibiotic-induced neuropsychiatric toxicity is relatively uncommon; yet, when it occurs, it can lead to severe morbidity ranging from dizziness and confusion to seizure and psychosis. However, the actual incidence rate of these adverse events may be higher due to underdiagnosis or misdiagnosis as they are commonly confused with clinical manifestations of different neuropsychiatric conditions. The incidence and mechanism of antibiotic-induced neuropsychiatric toxicity vary between different antibiotic classes and clinical presentation (i.e. neurotoxicity versus psychiatric toxicity). However, the exact mechanism by which antibiotics can cause neuropsychiatric toxicity remains unclear. This article reviews the epidemiology of antibiotic-induced neuropsychiatric toxicity, explores potential mechanisms of this adverse event, investigates variations in frequency and clinical presentations between different antibiotic classes causing neuropsychiatric toxicity, and discusses management strategies.

Background: Patients with severe asthma are often dependent on oral corticosteroids (OCS) and have frequent exacerbations. This article aims to report very long-term data of patients with severe eosinophilic asthma assessing asthma control, lung function, inhaled corticosteroid (ICS) dose reduction, and clinical and biological parameters of patients treated with mepolizumab.

Methods: Four cases of adult patients with severe eosinophilic asthma who were treated for 60 months or more with mepolizumab 100 mg/4 weeks, leading to the stable discontinuation of OCS, are presented. ICS dose, OCS dose and withdrawal date, lung function, eosinophil count, fractional exhaled nitric oxide, and asthma control test were recorded as well as exacerbations in the 12 months before commencing mepolizumab and in the 12 months before the last follow-up visit.

Results: Three of the patients were men, median age was 52.5 years (range 79-53), median length of asthma before mepolizumab start was 67.5 months (range 24-240), three had chronic rhinosinusitis without nasal polyposis and two were atopic. All had eosinophil counts >300 cells/μL at baseline. The median follow-up was 73.5 months (range 71-74), and OCS withdrawal from baseline occurred after a median of 13 months of mepolizumab treatment (range 12-39). A substantial reduction of ICS treatment was registered as well as improvement in asthma control test, fractional exhaled nitric oxide and functional parameters, and a significant reduction of exacerbations in the last 12 months before last visit was observed as compared to the 12 months before baseline (from a median of 4 (range 3-6) to 0; p=0.0286).

Conclusions: Mepolizumab could be a 'disease-modifying' agent, with high tolerability and a good efficacy profile in the long term.

The advent of immunotherapy, and in particular the use of immune-checkpoint inhibitors, has profoundly revolutionized the treatment of different cancers, including lung cancer. The use of immune-checkpoint inhibitors has prolonged survival in lung cancer with a strong benefit in a significant percentage of patients with non-small-cell lung cancer. Here, a clinical case of a patient who, despite testing negative for PD-L1, displayed a sustained complete response to immunotherapy treatment in advanced metastatic non-small-cell lung cancer is presented. Additionally, recent findings concerning the application of immunotherapy in this context are reviewed.

Background: Epilepsy is a persistent tendency to experience epileptic seizures and can lead to various neurobiological disorders, with an elevated risk of premature mortality. This study evaluates the efficacy of brivaracetam adjuvant therapy in patients with epilepsy.

Methods: A prospective observational multicentre study that was conducted in Pakistan from March to September 2022, by using a non-probability convenience sampling technique. The population consisted of 543 individuals with a diagnosis of epilepsy for whom adjunctive brivaracetam (Brivera; manufactured by Helix Pharma Pvt Ltd., Sindh, Pakistan) was recommended by the treating physician. The research sample was drawn from various private neurology clinics of Karachi, Lahore, Rawalpindi, Islamabad and Peshawar. Data originating from routine patient visits, and assessments at three study time points, were recorded in the study case report form.

Results: Across 18 clinical sites, 543 individuals participated, with a mean age of 32.9 years. The most prescribed dosages were 50 mg BD, followed by 100 mg BD. Notably, brivaracetam combined with divalproex sodium was the most prevalent treatment, followed by brivaracetam with levetiracetam. At both the 14th and 90th day assessments, a significant reduction in seizure frequency was observed, with 63.1% of individuals showing a favourable response by day 90. Treatment-naive individuals exhibited higher rates of seizure freedom and response compared with treatment-resistant individuals.

Conclusions: The study demonstrates the effectiveness of brivaracetam combination therapy in epilepsy management, with notable reductions in seizure frequency and favourable clinical responses observed, particularly in treatment-naive individuals.

Abnormal uterine bleeding (AUB) is an acute/chronic variation in the normal menstrual cycle that affects adolescents, women of reproductive age and perimenopausal women. AUB affects approximately 3-30% of reproductive-aged women worldwide, and reduces their quality of life and productivity whilst increasing the overall healthcare burden. Its management requires thorough medical evaluation and individualized treatment. Depending on the severity and cause of AUB, its treatment ranges from lifestyle modifications and hormonal therapies to more invasive procedures or surgery. Although hormonal therapy is the preferred first-line measure in AUB, the available pharmacological options have various adverse effects. There exists a need for safer and more efficient treatment regimens with high patient compliance to effectively treat AUB. Norethisterone, also known as norethindrone, is a widely used synthetic analogue of progestogen. Controlled release formulations of norethisterone/ norethisterone acetate help maintain constant drug levels in the blood and exert minimal side-effects; therefore, they are promising therapeutic agents for effective AUB management. The present review summarizes the epidemiology and diagnosis of AUB, with a focus on the safety, efficacy and tolerability of norethisterone/ norethisterone acetate in AUB management. We also report a case of AUB in a 40-year-old woman, who was treated with NETA tablets. The treatment resulted in favourable outcomes, and patient satisfaction.

Scientific research has often investigated the role of diet as a risk factor for cancer development. It is well known that cancer has a multifactorial origin in which several factors are involved: genetic predisposition, dietary factors, personal habits, and infectious and environmental factors. In this Commentary, the role of diet in cancer is discussed following the scientific evidence suggesting that excessive consumption of red meat and processed foods is correlated with a greater risk of contracting cancer. Nevertheless, public health strategies on nutrition in cancer prevention are struggling to take off. The decision to pursue a healthier diet, along with a healthier lifestyle, often comes when the cancer diagnosis is made and not before. On the other hand, scientific evidence demonstrates how nutritional support is increasingly important during oncological treatments. This paper highlights how far we are still from the global adoption of a healthy and sustainable food style from a health, economic, social and environmental perspective. Additionally, it highlights the ancient vision of the role of nutrition on cancer development in which diet is seen only as a possible risk factor, underestimating the protective role in terms of cancer prevention and the modulatory one once the oncological diagnosis has been made.

Introduction: Injectable extended-release formulations of luteinizing hormone-releasing hormone agonists (LHRHa) have simplified the treatment of prostate cancer with a satisfactory level of androgen castration. This study aims to determine the percentage of patients whose initial LHRHa prescription was renewed during follow-up, how many changed formulation and how their quality of life evolved.

Methods: This is an observational, prospective, multicentre study of men with prostate cancer who were to receive treatment with LHRHa (triptorelin every 3 or 6 months, leuprorelin every 3 or 6 months, or goserelin every 3 months) for 24 months. The treatment used was recorded and quality of life was assessed (QLQ-PR25 questionnaire) at four follow-up visits.

Results: A total of 497 men (median age 75 years) were evaluated. The median exposure to LHRHa was 24 months. The initial prescription was renewed in 95.7% at follow-up 1 and 75% at follow-up 4. The main reason for changing from a 6-month to a 3-month formulation was a preference for sequential treatment (according to the investigator) and to see the physician more frequently (according to the patient). The main reason for switching from the 3-month to 6-month formulation was simplification of treatment (according to the investigator) and for convenience (according to the patient). Findings in the QLQ-PR25 questionnaire revealed no changes in urinary or bowel symptoms, though an improvement in sexual activity was reported. Practically all investigators and patients were satisfied/very satisfied with the treatment.

Conclusion: Changes in formulation were scarce and generally justified by convenience factors or personal preferences. Patients maintained a good health status, with a high rate of retention of LHRHa treatment.

Clinical trial registration: Study number: A-ES-52014-224.A plain language summary is provided as supplementary material (available at: https://www.drugsincontext.com/wp-content/uploads/2024/05/dic.2024-2-2-Suppl.pdf).