Drugs in Context最新文献

Background: Brodalumab is a monoclonal antibody directed to the IL-17 receptor A, approved for the treatment of moderate-to-severe psoriasis. In phase III clinical trials, brodalumab showed clinical efficacy and a favourable safety profile. However, real-world data on brodalumab treatment are still limited. This study aimed to evaluate the real-world efficacy and safety of brodalumab treatment in a Portuguese population.

Methods: This is a retrospective, observational, multicentre study of patients with moderate-to-severe plaque-type psoriasis treated with brodalumab between January 2019 and August 2022. The follow-up period was 74 weeks. Brodalumab efficacy was accessed by the percentage of patients reaching the Psoriasis Area Severity Index (PASI) 75, 90 and 100 responses and by improvement in absolute PASI and Dermatology Life Quality Index (DLQI) scores. Drug survival of brodalumab treatment, causes of treatment discontinuation and adverse events were also reported.

Results: A total of 126 patients were included. Four weeks after treatment initiation, 83%, 57% and 29% of patients reached PASI 75, 90 and 100, respectively. These values increased to 96%, 93% and 66% at 74 weeks. A significant reduction in PASI score was observed after 4 weeks of brodalumab treatment and until week 74 (p<0.001). Quality of life measured by DLQI score significantly increased during the treatment period (p<0.001). Drug survival of brodalumab treatment was 82.5%, and secondary failure (8.5%) was the main reason for treatment discontinuation. The occurrence of adverse events was low and restricted to non-severe infectious.

Conclusion: This real-world data show that brodalumab is effective and safe for the treatment of moderate-to- severe psoriasis.

Background: This analysis assesses the effectiveness and tolerability profile of vericiguat in patients with heart failure with reduced ejection fraction (HFrEF) and implantable cardioverter-defibrillator, with an emphasis on the emergence of ventricular arrhythmias.

Methods: Retrospective analysis of patients with HFrEF and implantable cardioverter-defibrillator who started treatment with vericiguat in daily clinical practice in a tertiary university hospital in Spain.

Results: The study population comprised 14 patients treated since January 2023. At baseline, mean age was 77.0±7.0 years, 71.4% of patients were men and mean left ventricular ejection fraction was 32.1±5.4%. Regarding heart failure treatments, 13 (92.3%) patients were prescribed renin-angiotensin-aldosterone system inhibitors, mainly sacubitril-valsartan (61.5%), they were all prescribed aldosterone antagonists, 10 (71.4%) were prescribed β-blockers and 10 (71.4%) were prescribed sodium-glucose cotransporter-2 (SGLT2) inhibitors. After a mean duration of treatment with vericiguat of 12.4±5.3 months, two (14.3%) patients presented to the emergency department, one with hypotension and the other with impaired kidney function, and a further two (14.3%) patients were hospitalised, one of whom had decompensated heart failure. At baseline, four (28.6%) patients presented non-sustained/sustained ventricular tachycardia; at study end, this decreased to two patients (50% of patients with ventricular arrhythmias at baseline). Additionally, in one patient (25% of patients with ventricular arrhythmias at baseline), there was a substantial reduction in the number of episodes of ventricular arrhythmia. At study end, seven patients achieved the target dose of 10 mg daily and one patient discontinued vericiguat owing to hypotension.

Conclusions: Amongst patients with HFrEF and implantable cardioverter-defibrillator, vericiguat showed a good safety profile in addition to standard heart failure therapy, with low rates of adverse events. Moreover, a potential reduction in the risk of ventricular arrhythmias could also be obtained with vericiguat.

This Editorial reviews data on the efficacy and adverse effects of lecanemab amongst individuals with mild Alzheimer disease. Additionally, the recent controversy regarding the rejection by the EMA of a marketing authorization request for lecanemab, followed by its subsequent approval, is also discussed. The need for thoughtful discussions regarding the risks and benefits of this medication as well as the importance of developing Appropriate Use Recommendations and/or national guidelines for the use of lecanemab are also highlighted.

Background: Carvedilol has shown greater potency than propranolol as a β-blocker in managing cardiac conditions. However, its efficacy in reducing portal hypertension (PHTN) in patients with cirrhosis remains unclear. This study evaluates the efficacy and safety of carvedilol compared with propranolol in managing PHTN.

Methods: A systematic review and meta-analysis were conducted using PubMed, Scopus and Embase databases. Randomized controlled trials comparing carvedilol and propranolol were included. Primary outcomes were changes in hepatic venous pressure gradient, wedge hepatic venous pressure and free hepatic venous pressure. Secondary outcomes included heart rate, cardiac output and mean arterial pressure. Tertiary outcomes assessed adverse event incidences.

Results: Six randomized controlled trials involving 336 patients (171 carvedilol, 165 propranolol) were analysed. Carvedilol significantly reduced hepatic venous pressure gradient (mean difference (MD): 2.22 (95% CI 1.82-2.62); p<0.00001) and wedge hepatic venous pressure (MD: 2.38 (95% CI 1.92-2.84); p<0.00001). Propranolol significantly reduced cardiac output (MD: -0.60 (95% CI -0.74 to -0.45); p<0.00001). Mean arterial pressure was significantly lower in the carvedilol group (MD: 1.79 (95% CI 0.38-3.20); p=0.01). Adverse events, such as orthostatic hypotension and increased diuretic use, were more frequent in the carvedilol group but were manageable.

Conclusion: Carvedilol demonstrates superior efficacy in reducing PHTN compared with propranolol, with a slightly higher but tolerable adverse event profile. It may be considered the first-line treatment for PHTN. Further research is needed to validate long-term benefits and safety.

Membranous nephropathy (MN) is a kidney disease characterized by thickening of the glomerular basement membrane due to immune complex deposition, often leading to nephrotic syndrome and potentially progressing to end-stage renal disease. Traditional treatments, including corticosteroids and immunosuppressive agents, have significant side-effects and variable efficacy. Recently, obinutuzumab, a fully humanized monoclonal antibody targeting CD20, has emerged as a promising therapeutic option for MN. Herein, we review the pathophysiology of MN, the mechanism of action of obinutuzumab, clinical data supporting its use and highlight its potential as a game changer in MN treatment.

Background: Gastric cancer has a high mortality rate. Therapeutic management must be multidisciplinary to offer the patient the best, personalized strategy.

Patients and methods: We performed an observational study to evaluate the pathological response, survival and nutritional status in patients with resectable gastric cancer and candidates for perioperative chemotherapy with the fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT) regimen versus other regimens. The primary endpoints were pathological response rate, care continuity rate and survival outcomes. A total of 96 patients attending the Hospital "Policlinico San Matteo" in Pavia (Italy) between January 2012 and August 2022 were selected for the study.

Results: Regarding pathological response rates, the best rate (TRG-0) was recorded in the FLOT group with a percentage of 6.2% compared with 4.7% in the NO-FLOT arm (p=0.052). The highest failure rate to complete the post-operative phase was 75% in the NO-FLOT group and only 25% in the FLOT group (p=0.007). Survival outcomes were better in the FLOT group with a median disease-free survival of 30 versus 22.2 months (p=0.586).

Conclusions: Despite the limitations, the results obtained were consistent with the medical literature and confirmed the effectiveness of the FLOT chemotherapy in real life. Nevertheless, some questions remain: the application in elderly patients, the addition of immunotherapy in patients with microsatellite instability or with high PD-L1 levels, comparison with chemoradiotherapy in junctional cancers and real cure rates. The FLOT regimen has revolutionized the treatment of resectable gastric cancer, but caution is needed before considering it an absolute standard of care.

Background: Filgotinib, an oral Janus kinase 1 preferential inhibitor, has been shown to be an effective treatment for ulcerative colitis (UC) in pre-registration studies. We aimed to describe the treatment population, effectiveness and safety of filgotinib in a real-world cohort of patients with UC.

Methods: A retrospective observational cohort evaluation was conducted across nine UK inflammatory bowel disease centres. Baseline demographic and clinical data, clinical disease activity scores, endoscopic activity indices, and biomarkers (C-reactive protein and faecal calprotectin) were collected at baseline, at 8-12 weeks after initiation (post-induction) and during maintenance (the most recent review) where available. Effectiveness outcomes were assessed in patients with combined clinical disease activity and objective evidence of inflammation at filgotinib initiation.

Results: Data were analysed for a total of 286 patients with a median follow-up time of 229 (IQR 113-324) days. The median age at filgotinib initiation was 38 (IQR 27-51) years, 64% were men and median disease duration was 5.1 (IQR 1.9-10.5) years; 56% had previous exposure to advanced therapies (biologics and small molecule) and 6% previously received tofacitinib. At the post-induction review, clinical response and remission were achieved in 65% and 51% of patients, respectively. There was a reduction in biomarkers and 78% of patients using corticosteroids at baseline were steroid-free. Persistence on filgotinib at 12 months was 66%. Adverse events were recorded in 30 patients with 8 patients discontinuing filgotinib as a result of an adverse event.

Conclusions: In a large real-world cohort of patients with UC, filgotinib appears to be effective and well-tolerated.

Background: Aliaxin fillers (HA_ALI), produced by IBSA Farmaceutici Italia SrL (Italy), are biodegradable, non-pyrogenic, 1,4-butanediol diglycidyl ether cross-linked hyaluronic acid (HA) hydrogels. The formulations are tailored for different clinical indications, ensuring precise and natural outcomes. Their cohesivity and tissue integration capabilities are associated with relatively few adverse events (AEs), supporting their widespread use in aesthetic treatments. This article examines the real-world safety profile of HA_ALI fillers derived from worldwide post-marketing surveillance data.

Methods: Post-marketing surveillance was registered by the manufacturer from January 2018 to September 2023. During this period, product complaints were globally gathered from healthcare practitioners and consumers, relating to technical issues or safety and product-related adverse events.

Results: No discernible trend or substantial escalation in AEs across the entire product range were observed during the surveillance period (p>0.05). No statistically significant increases (p>0.05) in the frequency or severity of safety incidents and AEs were observed. The most frequently observed AEs were oedema (26%) and swelling (19%).

Conclusion: The analysed data further support and confirm the high safety profile of the HA_ALI fillers for different approaches in aesthetic medicine. This evaluation also highlights the importance of post-marketing analysis by continuing to foster a robust understanding of products currently used in daily clinical practice.

Inclisiran is a synthetic small interfering RNA (siRNA) that inhibits the production of proprotein convertase subtilisin/kexin 9 (PCSK9) in hepatocytes by silencing the translation of PCSK9 mRNA. The result of this mechanism is a decrease in PCSK9 synthesis resulting in decreased degradation of the LDL receptor, leading to more LDL receptors being available to clear LDL cholesterol (LDL-C) from the circulation. Inclisiran received FDA approval in 2021 and EMA approval in 2020. The indication for inclisiran use is as an adjunct to diet and statin therapy for the treatment of adults with primary hyperlipidaemia, including those with heterozygous familial hypercholesterolaemia to reduce LDL-C. Inclisiran has demonstrated consistent LDL-C lowering in the range of 44-54%. Furthermore, inclisiran has been demonstrated to be a safe medication with indications of significant or serious adverse events when compared to placebo. Inclisiran is given as an initial subcutaneous dose followed by a repeat dose at 3 months and every 6 months thereafter. The 2022 American College of Cardiology Expert Consensus Decision Pathway includes inclisiran as an option for non-statin therapy in addition to maximally tolerated statin therapy in those at very high risk of atherosclerotic cardiovascular disease or those with LDL-C >190 mg/dL. The ORION-4, VICTORION-1 PREVENT and VICTORION-2 PREVENT trials are ongoing and designed to evaluate the ability of inclisiran to reduce major cardiovascular events in addition to LDL-C lowering but will not be completed for a few years.

Psychomotor agitation (PMA) is a prominent clinical issue frequently observed in various psychiatric and neurological conditions, including schizophrenia, bipolar disorder, Parkinson disease, dementia and substance use disorder. Characterized by motor restlessness, anxiety and irritability, PMA can rapidly escalate into aggression and violence, necessitating prompt intervention to ensure patient and caregiver safety. The prevalence of PMA in psychiatric emergency settings ranges from 4.3% to 10%, imposing a substantial burden on healthcare systems. Despite the critical nature of PMA, there is a lack of standardized treatment protocols, particularly concerning the use of liquid formulations of antipsychotics such as liquid promazine, which may offer unique advantages in emergency care. This review aims to provide a comprehensive analysis of the existing literature on the efficacy, safety and tolerability of liquid antipsychotics, with a particular focus on promazine, in the management of PMA. An extensive literature search was conducted across publicly available databases with no time limitations to ensure the inclusion of all relevant articles. The findings suggest that liquid promazine offers several benefits, including ease of administration, rapid onset of action and improved patient compliance, making it a valuable option in acute PMA management. However, the review also highlights the need for future research, particularly long-term studies and head-to-head comparisons with other antipsychotics, to better establish the clinical utility of liquid promazine. Future research should focus on expanding the evidence base for liquid antipsychotic formulations, which will contribute to improved clinical outcomes in the management of PMA.