Clinical therapeutics
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Clinical therapeutics · Apr 2015
ReviewNew FDA-Approved Disease-Modifying Therapies for Multiple Sclerosis.
Interferon injectables and glatiramer acetate have served as the primary disease-modifying treatments for multiple sclerosis (MS) since their introduction in the 1990s and are first-line treatments for relapsing-remitting forms of MS (RRMS). Many new drug therapies were launched since early 2010, expanding the drug treatment options considerably in a disease state that once had a limited treatment portfolio. The purpose of this review is to critically evaluate the safety profile and efficacy data of disease-modifying agents for MS approved by the US Food and Drug Administration (FDA) from 2010 to the present and provide cost and available pharmacoeconomic data about each new treatment. ⋯ With expansion of new treatments, patients and providers now have multiple options and improved flexibility in managing MS. The relative place in therapy of new treatments is unknown, and treatment decisions are largely based on patient preference, efficacy, and risk potential. The cost of treating MS continues to be high, even with more treatment options available.
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Clinical therapeutics · Apr 2015
ReviewThe Next Immune-Checkpoint Inhibitors: PD-1/PD-L1 Blockade in Melanoma.
Blocking the interaction between the programmed cell death (PD)-1 protein and one of its ligands, PD-L1, has been reported to have impressive antitumor responses. Therapeutics targeting this pathway are currently in clinical trials. Pembrolizumab and nivolumab are the first of this anti-PD-1 pathway family of checkpoint inhibitors to gain accelerated approval from the US Food and Drug Administration (FDA) for the treatment of ipilimumab-refractory melanoma. Nivolumab has been associated with improved overall survival compared with dacarbazine in patients with previously untreated wild-type serine/threonine-protein kinase B-raf proto-oncogene BRAF melanoma. Although the most mature data are in the treatment of melanoma, the FDA has granted approval of nivolumab for squamous cell lung cancer and the breakthrough therapy designation to immune- checkpoint inhibitors for use in other cancers: nivolumab, an anti-PD-1 monoclonal antibody, for Hodgkin lymphoma, and MPDL-3280A, an anti-PD-L1 monoclonal antibody, for bladder cancer and non-small cell lung cancer. Here we review the literature on PD-1 and PD-L1 blockade and focus on the reported clinical studies that have included patients with melanoma. ⋯ This family of immune-checkpoint inhibitors benefits not only patients with metastatic melanoma but also those with historically less responsive tumor types. Although a subset of patients responds to single-agent blockade, the initial trial of checkpoint-inhibitor combinations has reported a potential to improve response rates. Combination therapies appear to be a means of increasing response rates, albeit with increased immune-related adverse events. As these treatments become available to patients, education regarding the recognition and management of immune-related effects of immune-checkpoint blockade will be essential for maximizing clinical benefit.
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Clinical therapeutics · Apr 2015
The Affordable Care Act: how can we know whether the intended consequences are occurring and the unintended ones are being avoided?
When the Affordable Care Act (ACA) was signed into law on March 23, 2010, policymakers intended that it would improve access to care by lowering the uninsured rate, improve health care quality, and lower costs. Now, 4 years later, researchers and policymakers need to ask whether those intentions have been realized or whether the ACA has produced unintended consequences that affect patient care. This article raises the importance of assessing what changes in patient access and clinical care have occurred, points out how challenging those assessments may be to conduct, and concludes with a call to action about how those challenges might be addressed.
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Clinical therapeutics · Mar 2015
Meta AnalysisEffect of the urinary tryptin inhibitor ulinastatin on cardiopulmonary bypass-related inflammatory response and clinical outcomes: a meta-analysis of randomized controlled trials.
Cardiopulmonary bypass (CPB) can cause systemic inflammatory responses and a series of subsequent complications that may harm patients. The aim of this study was to explore the effects of ulinastatin on inflammatory responses and clinical outcomes of CPB via a meta-analysis of published randomized controlled trials. ⋯ This meta-analysis found that changes in inflammatory cytokines occurred in a time-dependent manner and that the use of ulinastatin resulted in decreased duration of mechanical ventilation with CPB compared with placebo.
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Clinical therapeutics · Mar 2015
Randomized Controlled TrialEfficacy and tolerability of intranasal fentanyl spray in cancer patients with breakthrough pain.
The aims of this study were to explore the efficacy of intranasal fentanyl spray* (INFS) 400 μg to evaluate 12-week tolerability of the nasal mucosa and to explore safety data for all dose strengths of INFS in patients with cancer-related breakthrough pain (BTP). ⋯ INFS 400 μg is effective and nasal tolerability and overall safety profile is acceptable during 12 weeks of use. ClinicalTrials.gov identifier: NCT01429051.