Core Evidence最新文献

Chronic thromboembolic pulmonary hypertension (CTEPH) is classified as group-4 pulmonary hypertension caused by organized thrombi in pulmonary arteries and vasculopathy in nonoccluded areas leading to right heart failure and death. In addition to chronic anticoagulation therapy, each patient with CTEPH should receive treatment assessment starting with evaluation for pulmonary endarterectomy (PEA), which is the guideline recommended treatment. There is increasing experience with balloon pulmonary angioplasty (BPA) for inoperable patients; this option, like PEA, is reserved for specialized centers with expertise in this treatment method. Inoperable patients are candidates for targeted drug therapy. Riociguat remains the only approved medical therapy for CTEPH patients deemed inoperable or with persistent pulmonary hypertension after PEA. The role of riociguat therapy preoperatively or in tandem with BPA is currently under investigation. The purpose of this review is to evaluate the safety and efficacy of riociguat in the treatment of CTEPH.

Introduction: Antineoplastic drugs may induce several side effects, including chemotherapy-induced nausea and vomiting (CINV). Two neurotransmitters play a central role in mediating the emetic response: serotonin acting on the 5HT3 receptor and the substance P targeting the NK1 receptor. Indeed, a combination of a 5HT3 receptor antagonist (5HT3-RA) and a NK1 receptor antagonist (NK1-RA) together with dexamethasone has been shown to be very effective. In fact, this combination is actually widely used and recommended for CINV prophylaxis for highly emetogenic cisplatin-based adriamycin/cyclophosphamide (AC) and carboplatin-based regimens. NEPA (netupitant/palonosetron) is the only fixed combination antiemetic available and it is composed by the long-lasting second-generation 5HT3-RA palonosetron and the highly selective NK1-RA netupitant.

Aim: The aims of this short review were to analyze the role of NEPA in CINV prophylaxis and management taking in account the risk factors related to the patient and to the antineoplastic treatment.

Evidence review: CINV development is not only correlated to the emetogenic potential of the antineoplastic drugs but is also very influenced by the patient characteristics and history, such as gender, age, alcohol intake, nausea during pregnancy and motion sickness. In pivotal and post-registration studies, NEPA has demonstrated to be effective and safe in both highly and moderately emetogenic chemotherapy.

Conclusion: A proper assessment of both chemotherapy- and patient-related risk factors is paramount to properly evaluate an appropriate prophylaxis of CINV and NEPA by simplifying the therapy, guarantees fully adherence to antiemetic guidelines, and consequently improves the control of CINV, especially in high risk patients.

Introduction: Selective blockade of the integrins and mucosal adhesion molecules is a promising therapeutic strategy for ulcerative colitis (UC). Vedolizumab (VDZ), a humanized IgG1 monoclonal antibody against α4β7 integrin, selectively blocks the trafficking of the leukocytes into the gastrointestinal tract through its binding with the α4β7 integrin.

Aim: In this review, we provide an overview of the unique mechanism of VDZ, along with its efficacy, safety, and pharmacokinetic and pharmacodynamic data obtained from clinical trials, observational studies, and meta-analyses.

Evidence review: A positive exposure-efficacy relationship with regard to clinical remission and clinical response was apparent in VDZ induction therapy. No drug-specific safety signals are currently available.

Place in therapy: VDZ has been shown to be effective as first- or second-line induction and maintenance therapy in UC.

Conclusion: VDZ is a safe and effective treatment option for patients with UC. Prolonged VDZ induction therapy may contribute to improved outcomes in patients with UC, particularly those previously treated with tumor necrosis factor-α. Prospective head-to-head study of VDZ and other biologics would alter the positioning of VDZ much more clearly.

Oral anticoagulant therapy for stroke prevention in atrial fibrillation patients has been remarkably changed by the introduction of non-vitamin k oral anticoagulants (NOAC). Apixaban was the third NOAC introduced to clinical practice. Aim was to outline the current evidence for Apixaban in stroke prevention in atrial fibrillation patients in the randomized trials and real-world data. Apixaban has been shown to be superior to warfarin in preventing stroke and systemic embolism and causes significantly less major bleeding based on large randomized trials. These data are confirmed in real-world studies. Apixaban has been shown to be safe and effective in atrial fibrillation patients in acute coronary syndrome or undergoing PCI in combination with a P2Y₁₂ inhibitor. Regarding expanded use of apixaban also in valvular heart disease patients, there is still missing knowledge in relation to the safety and efficacy of apixaban which is being addressed by ongoing randomized clinical trials.

Introduction: Acute myeloid leukemia (AML) remains a disease with high mortality, especially for older patients and those with relapsed/refractory (R/R) disease. With recent advances in molecular testing, targeting particular leukemogenic mutations such as those occurring in isocitrate dehydrogenase (IDH) became possible. Enasidenib is a new small-molecule inhibitor of mutant isocitrate dehydrogenase-2 (IDH2). Aim: The objective of this article is to review the evidence for the use of enasidenib in R/R AML, as well as to outline future directions of enasidenib therapy. Evidence Review: Enasidenib was approved in August 2017, after a successful Phase I/II trial showing an overall response rate (ORR) of 40.3% in R/R disease, with 19.3% of patients achieving complete remission (CR). Enrollees in the trial were mostly older adults. The most prominent toxicities were hyperbilirubinemia and IDH-differentiation syndrome (IDH-DS), though the drug was generally well tolerated and the maximum tolerated dose was not reached. A Phase III trial is currently ongoing. Conclusion: Enasidenib provides a new therapeutic option for patients with R/R AML. Further studies are ongoing to ascertain its role in combination with other agents and newly diagnosed disease.

[This corrects the article on p. 11 in vol. 12, PMID: 28356904.].