Risultati per: FDA approva un nuovo trattamento per l’emicrania

Circulation, Volume 148, Issue Suppl_1, Page A18533-A18533, November 6, 2023. Introduction:Nivolumab and Ipilimumab are human monoclonal antibodies that target cell surface PD1 and anti-CTLA-4 receptors respectively. Nivolumab and ipilimumab combination is used for metastatic small cell lung carcinoma, advanced renal cell carcinoma and metastatic melanoma. The pre-approval CHECKMATE trials have underestimated the occurrence of cardiovascular adverse events (AEs). In contradiction, post-marketing studies have demonstrated a higher incidence of cardiac AEs, particularly myocarditis.Therefore, it is important to establish a post-marketing safety profile of these medications.Methods:We investigated the cardiovascular AEs of nivolumab and ipilimumab using U.S. Food and Drug Administration Adverse Event Reporting System (FAERS). Healthcare professionals (HCPs) reported 79.73% and 80.92% of AEs until March 2023 for nivolumab and ipilimumab respectively. We conducted further subgroup analysis of cardiovascular AEs in male, females as well as in three age groups: 18-64, 65-85 and >85 years.Results:Amongst the cardiovascular AEs reported by HCPs, myocarditis was reported in 905 (1.55 %) in nivolumab vs 445 (1.72%) in ipilimumab group. There were higher reports of other cardiovascular AEs including heart failure (1.15% vs 0.74%), pericarditis/pericardial effusion (1.19% vs 0.6% ), myocardial infarction (0.18% vs 0.71%), cardiomyopathy (0.36% vs 0.29%), cardiac arrest (0.41% vs 0.53%) and cardiac death (0.01% vs 0.02%) in nivolumab vs ipilimumab. On sub-group analysis, we observed higher incidence of myocarditis in females (1.54% vs 1.6%) males (1.73% vs. 1.84%) and in patient with age 18-65 years (1.17% vs 1.15%) in both nivolumab vs ipilimumab group as compared to previous studies.Conclusions:The reported events of myocarditis were significantly higher in FAERS reporting as compared to the CHECKMATE trials (

Circulation, Volume 148, Issue Suppl_1, Page A16736-A16736, November 6, 2023. Introduction:One-year mortality risk for a pulmonary arterial hypertension (PAH) patient is the most substantial. Accordingly, the initial risk stratification should be the most accurate to ensure appropriate aggressiveness of the primary treatment choices. According to PAH guidelines, the European 3-strata system is recommended at baseline for risk assessment. However, the US REVEAL2.0 and REVEAL Lite risk scores also provide high performances. Yet, comparison of risk assessment performances at baseline in the same dataset of patients is still missing.Hypothesis:REVEAL 2.0 provide higher discrimination performances than the European 3-strata system at baseline. We aim to compare the discrimination power at baseline of the currently available tools.Methods:Treatment naïve PAH patients from 6 PAH trials were provided by the FDA and harmonized (AMBITION n=500, ARIES n=126, PATENT n=221, PHIRST n=77, GRIPHON n=231, and SERAPHIN n=270). Kaplan-Meier and log-rank tests were performed for each of the following tools: noninvasive FRENCH method (FR), European 3-strata system (E3), COMPERA2.0 4-strata (CO), REVEAL2.0 (RE), and REVEAL Lite (RL). Their C-indices were compared. A total of 100 bootstrap samples were obtained from the original data providing a robust method for comparing across the different tools.Results:Among the 1,425 patients, 78% were female, 54% NYHA 3-4 with a median age of 51(38, 64) yo, 6-min walking distance of 365(295, 418)m, mPAP of 49(38, 59) mmHg, PVR 9.3(6.2, 13.5) WU. At baseline, the C-index for FR, CO, E3, RL, and RE were 0.64, 0.67, 0.68, 0.69, 0.73, respectively. Out of the 100 bootstrap samples, 99% led to a better C-index for RE compared to E3, with a statistically significant paired t-test (p

Circulation, Volume 148, Issue Suppl_1, Page A18569-A18569, November 6, 2023. Introduction:Despite robust evidence for, and Food and Drug Administration (FDA) approval of sodium-glucose cotransporter-2 inhibitors (SGLT2i) for heart failure with preserved and mildly reduced ejection fraction (HFpEF/HFmrEF), use of this therapy is suboptimal.Hypothesis:We aimed to determine 1) prescribing context (inpatient/outpatient) and prescriber type of SGLT2i; 2) patient and provider level predictors of SGLT2i prescription in the year following FDA approval.Methods:All patients in a diverse, multi-state (Ohio and Florida), multi practice/hospital integrated system who had least 1 ambulatory encounter for HF and documented EF >40% were included. Data come from the electronic health record. We compared patients who were prescribed SGLT2i in the year post FDA approval 2/24/22-2/24/23 against those who were not using multivariable logistic regression to assess independent predictors of SGLT2i prescription.Results:20,255 patients with HFpEF/HFmrEF were included in the study. Mean age 73±9 yrs, female (49.8%), Black (17.4%), DM2 (34%), AFib (43%), CKD (35%), baseline medications: BB (52.4%), ACEi/ARB (41%), MRA (19.7%), ARNI (6.5%), SGLT2i (3.2%). There were 1118 (5.6%) patients were newly prescribed SGLT2i in the study period. SGLT2i were most commonly initiated by cardiology 54.2%, general medicine 25.3% and endocrinology 8.5%. Of prescriptions, 82.9% were outpatient, 17.1% inpatient. Independent patient level predictors of SGLT2i prescription were DM2 2.82 (2.09-3.82), p

New England Journal of Medicine, Ahead of Print.

This Viewpoint discusses the US Food and Drug Administration’s Project Optimus, which focuses on new oncology drug dose optimization and examines concerns about the accelerated postmarketing approval of adjusted dosing of oncologic drugs.

Background
Recent reports of the utilisation of pyrvinium pamoate (PP), an FDA-approved anti-helminth, have shown that it inhibits pancreatic ductal adenocarcinoma (PDAC) cell growth and proliferation in-vitro and in-vivo in preclinical models. Here, we report about an ongoing phase I open-label, single-arm, dose escalation clinical trial to determine the safety and tolerability of PP in PDAC surgical candidates.

Methods and analysis
In a 3+3 dose design, PP is initiated 3 days prior to surgery. The first three patients will be treated with the initial dose of PP at 5 mg/kg orally for 3 days prior to surgery. Dose doubling will be continued to a reach a maximum of 20 mg/kg orally for 3 days, if the previous two dosages (5 mg/kg and 10 mg/kg) were tolerated. Dose-limiting toxicity grade≥3 is used as the primary endpoint. The pharmacokinetic and pharmacodynamic (PK/PD) profile of PP and bioavailability in humans will be used as the secondary objective. Each participant will be monitored weekly for a total of 30 days from the final dose of PP for any side effects. The purpose of this clinical trial is to examine whether PP is safe and tolerable in patients with pancreatic cancer, as well as assess the drug’s PK/PD profile in plasma and fatty tissue. Potential implications include the utilisation of PP in a synergistic manner with chemotherapeutics for the treatment of pancreatic cancer.

Ethics and dissemination
This study was approved by the Thomas Jefferson Institutional Review Board. The protocol number for this study is 20F.041 (Version 3.1 as of 27 October 2021). The data collected and analysed from this study will be used to present at local and national conferences, as well as, written into peer-reviewed manuscript publications.

Trial registration number
ClinicalTrials.gov: NCT05055323.

This Viewpoint discusses why the US Food and Drug Administration (FDA) should include e-cigarettes in its proposed cap of the nicotine concentration in combustible cigarettes to address the public health problem of vaping among adolescents.

A pochi vengono prescritti i nuovi farmaci che riducono attacchi

A pochi vengono prescritti i nuovi farmaci che riducono attacchi

San Raffaele Roma, Italia prima al mondo per pazienti coinvolti

Una nuova ricerca collega le proteine anomale che si accumulano nel cervello con una forma di suicidio cellulare innescata da una molecola specifica Meg3: la sua inibizione prevenire la morte neuronale

Potrebbero essere usati come un indicatore precoce della cefalea