Drugs in Context最新文献

Until recently, treatment options for patients with recurrent or metastatic endometrial cancer (EC) were limited. First-line treatment is usually based on carboplatin and paclitaxel and there was no standard second-line therapy following platinum failure. However, the introduction of immunotherapy has expanded both first-line and later-line options for EC and made determination of mismatch repair status essential. We describe the case of a 56-year-old woman with deficient mismatch repair/microsatellite instability EC who did not respond to first-line treatment with carboplatin and paclitaxel but had a high response to subsequent immunotherapy with dostarlimab. There was initial pseudoprogression of one target lesion but marked improvement in quality of life. This article is part of the New treatment options for advanced endometrial carcinoma Special Issue: https://www.drugsincontext.com/special_issues/new-treatment-options-for-advanced-endometrial-carcinoma.

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease that occurs more frequently in children but can also manifest in adults. Approximately 15-20% of children are affected worldwide. Persistent AD may be present in approximately 50% of patients during childhood. Despite the pivotal studies, there are not enough real-life studies using dupilumab, especially in Latin American countries. This study was performed in Brazil and is essential for evaluating this population. The objective of the study was to understand the real-life efficacy and safety of using dupilumab in patients with moderate or severe AD.

Methods: Observational, descriptive study based on the biweekly evaluation of 100 patients using the immunobiological dupilumab in an infusion clinic for 16 consecutive weeks. Data collection was conducted from June 2020 to March 2022. To evaluate each sequential SCORing Atopic Dermatitis (SCORAD) value, a repeated measures analysis of variance was performed, with a value of p<0.0001.

Results: There was a significant decrease in SCORAD values from the second week of treatment. In 16 weeks, 80% of patients achieved SCORAD-50 and 37% achieved SCORAD-75. Regarding adverse effects, 22% of patients had conjunctivitis, 11% had facial erythema, 1% had herpes simplex and 1% had hypochromia at the application site. Regarding efficacy, the results showed a reduction in SCORAD value by 67.4% in 16 weeks, 72% of patients achieved SCORAD <25, that is, mild atopic dermatitis.

Conclusion: This study identified that dupilumab was effective in real life, even outside of the controlled environments of pivotal studies. Additionally, despite conjunctivitis being a common adverse event, no patient required treatment discontinuation.

Background: Hyperhidrosis (HH) is a condition characterized by excessive sweating beyond the physiological needs of thermoregulation. HH can be classified as primary (idiopathic) hyperhidrosis (PHH) or secondary hyperhidrosis (SHH), which is associated with underlying medical conditions, medications or systemic disorders. This narrative review provides an updated overview of PHH, with a focus on epidemiology, aetiopathogenesis, clinical manifestations, diagnostic approaches and current management strategies, particularly highlighting pharmacological and procedural treatment options.

Methods: A literature search was conducted in February 2025 across Ovid Medline, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL) using the key term "hyperhidrosis". The review included observational studies, clinical trials, narrative reviews, guidelines and meta-analyses published in the past 10 years. Additional references were identified through manual searches of relevant bibliographies.

Results: The global prevalence of PHH is estimated to range between 0.072% and 9%, with PHH accounting for 93% of all HH cases. Whilst the precise pathophysiology remains unclear, PHH is believed to result from sympathetic overactivity, whereas SHH is associated with endocrine, neurological, infectious, malignant and medication-induced causes. PHH is diagnosed clinically and distinguishing between primary and secondary forms is essential. Management options vary based on severity, ranging from topical therapies (antiperspirants, anticholinergics), systemic medications (oral anticholinergics, adrenergic modulators), device-based interventions (iontophoresis, microwave thermolysis), injectable therapies (botulinum toxin) and surgical approaches (sympathectomy, excision, liposuction/curettage). Whilst these interventions can significantly improve symptoms and quality of life, long-term efficacy, recurrence and adverse effects remain concerns.

Conclusion: PHH significantly impacts the quality life of patients contributing to both physical discomfort and psychosocial distress. An individualized, multi-modal approach is crucial to optimizing management. Further research is warranted to refine existing therapies and evaluate emerging treatment modalities for improved long-term outcomes.

Paediatric dacryocystitis, often linked to congenital nasolacrimal duct obstruction, may require surgical intervention if local conservative treatment is ineffective. This case series evaluated a local conservative treatment approach in five infants (1-12 months). Patients received Crigler massages twice daily, a 0.01% hypochlorous acid-based disinfectant spray and moxifloxacin eye drops during acute episodes. Symptoms progressively improved, with complete resolution within 6-9 months and no recurrence. The regimen was well tolerated and no surgical intervention was needed. These findings suggest that this local conservative strategy may serve as an effective first-line treatment, potentially reducing the need for invasive procedures in paediatric dacryocystitis management.

Platinum compounds play a crucial role in the treatment of solid tumours in paediatric patients, significantly improving survival rates. However, these treatments can result in hearing loss as a side-effect that can significantly impact the quality of life of young cancer survivors. Whilst the therapeutic benefits of platinum compounds in paediatric oncology are indisputable, addressing the challenge of ototoxicity remains a priority. Early and regular auditory function assessments, with tools such as audiometry, otoacoustic emissions and auditory brainstem response testing, are critical during platinum-based therapy, playing key roles in the early detection of hearing loss. Interdisciplinary collaboration amongst paediatric oncologists, audiologists and otolaryngologists is essential for optimal management and to minimize the long-term consequences of hearing loss. This narrative review concludes that, whilst platinum-based chemotherapeutic agents demonstrate significant therapeutic efficacy in paediatric malignancies, platinum-induced ototoxicity remains a substantial clinical challenge. Continued research into prevention, monitoring and treatment strategies is essential for preserving hearing and improving the overall quality of life for survivors of childhood cancer.

This is a collection of clinical experiences exploring the real-world effectiveness of a hydrophilic curcumin-based oral formulation (CHC, Diabec^®) in the management of macular oedema across diverse retinal conditions, including diabetic macular oedema, central serous chorioretinopathy, branch retinal vein occlusion and Irvine-Gass syndrome. Eight cases reported significant improvements in best-corrected visual acuity and central macular thickness, with complete resolution of oedema in some instances. CHC was well tolerated, with no adverse effects reported. These findings suggest that CHC is a safe and effective adjunct or standalone therapy for chronic or refractory macular oedema, enhancing anatomical and functional outcomes in real-world settings.

Upadacitinib is a Janus kinase (JAK) inhibitor approved for the treatment of different rheumatic diseases, including axial spondyloarthritis (axSpA). In phase III clinical trials, upadacitinib was associated with rapid and significant improvement in disease parameters, including scores for pain, function and mobility, signs of structural damage, and patient-reported outcomes, and had an overall incidence of adverse events similar to that in the placebo group. Improvement in axSpA disease severity was observed in both biologic-naive patients and those with prior biologic exposure, and this improvement was sustained during open-label treatment. Indirect comparisons with other agents suggest that upadacitinib is more effective than biologics and other JAK inhibitors in patients with axSpA and is associated with the lowest number-needed-to-treat. Long-term safety data indicate that upadacitinib is well tolerated in patients with axSpA, with a low rate of infections, malignancies, major adverse cardiovascular events and thromboembolism. Four case studies described here illustrate the effectiveness of upadacitinib in a range of real-world patients with axSpA, including patients with early disease and those who have been pre-treated with biologics.

Background: The 2018 American Society of Clinical Oncology/College of American Pathologists guidelines classified immunohistochemistry (IHC) 1+ or 2+, FISH-negative breast cancer as HER2-low. To date, only a few studies have investigated the role of HER2-low status in patients with hormone receptor positive/HER2^- (HR⁺/HER2^-) metastatic breast cancer (MBC) during CDK4/6 inhibitor (CDK4/6i) therapy.

Methods: This is a multicentre, retrospective cohort study analysing data from patients with HR⁺/HER2-low and HR⁺/HER2-0 MBC treated with CDK4/6i as first-line or second-line therapy at the Oncology Units of IRCCS San Matteo Hospital and ICS Maugeri IRCCS in Pavia, Italy, from January 2017 to October 2023. The aim was to assess the activity and effectiveness of CDK4/6i in a real-life setting.

Results: Of the 241 patients included, 240 (99.6%) were women. The median age at diagnosis was 57 years (IQR 48-65 years). Most patients had pM M0 (70.5%). At presentation, 112 (46.5%) had HER2-low and 129 (53.5%) had HER2-0 status. CDK4/6i were administered as first-line therapy in 89.2% of patients and as second-line therapy in 10.8% of patients, with palbociclib (61.4%) being the most common. The median progression-free survival during CDK4/6i therapy was 36.3 months (95% CI 23.6 months to not reached), while the median overall survival was 60.5 months (95% CI 54.4 months to not reached). Progression-free survival differed significantly between palbociclib and abemaciclib/ribociclib (24.4 versus 53.7 months; p=0.0109) and between first-line and second-line therapy (40.5 versus 21.2 months; p=0.0466).

Conclusion: CDK4/6i are effective in both HER2-low and HER2-0 MBC, with HER2-low potentially benefiting more from first-line therapy.

Eosinophilic granulomatosis with polyangiitis is a rare systemic vasculitis associated with asthma, eosinophilia and multi-organ involvement. This case report describes a 69-year-old male with severe, poorly controlled asthma who was diagnosed with eosinophilic granulomatosis with polyangiitis. Despite treatment with mepolizumab 300 mg and optimized inhaled therapies, comprising high-dose inhaled corticosteroids and long-acting β2-agonists and a long-acting muscarinic antagonist in two separate inhalers, the patient exhibited poor asthma control, accompanied by exacerbations of symptoms, increased reliance on oral corticosteroids, and a decline in lung function. Consequently, a comprehensive, multidisciplinary approach targeting comorbidities was deemed necessary, including the management of chronic rhinosinusitis with nasal polyps. Following a switch to a single-inhaler triple therapy, the patient demonstrated significant improvements in terms of asthma control, respiratory function, oscillometric measurements and fractional exhaled nitric oxide reduction. This report underscores the significance of personalized treatment strategies and a treatable-traits approach targeting small airway dysfunction, persistent airflow limitation and type 2 inflammation for effective disease management. A literature review on therapeutic advancements and clinical implications is also presented to provide clinicians with useful insights into managing severe asthma and single-inhaler triple therapy placement.

Objective: This systematic review examines psychiatric medications approved by the FDA for anxiety disorders, post-traumatic stress disorder (PTSD) and obsessive-compulsive disorder (OCD) from 2008 to 2024 and describes the mechanism of action, indications for both labelled and off-label uses, evidence for efficacy, dosing and adverse effects for each medication.

Methods: The methodology involved a literature search of the PubMed database for studies published from 1 January 2008 to 31 December 2024 on FDA-approved psychiatric medications and phase III pipeline medications, using the keywords: "anxiety" OR "PTSD" OR "OCD" AND "psychopharm*" OR "medic*" OR "pharm*". The authors conducted independent assessments of the resulting articles and reached a consensus on eligible studies to include in this systematic review.

Results: Our review revealed that, in the past 16 years, the FDA approved only two medications for anxiety disorders (a delayed-release form of duloxetine for generalized anxiety disorder and an extended-release form of lorazepam) and none for PTSD or OCD. We also identified 14 pipeline medications for anxiety disorders, eight for PTSD and one for OCD, all of which are currently in phase III clinical trials.

Conclusion: Our results showed a paucity of new medications for anxiety disorders and none for PTSD and OCD in the past 16 years. However, phase III psychiatric medications for anxiety disorders, PTSD and OCD seem to show several agents with novel mechanisms of action, various modes of administration, and improved side-effect profiles.